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Their carrier clock is not a paper figure axis or clinical follow-up time; they must be shown as reference views outside the prediction interface.","Figure 1 digitized components are raster approximations, not patient-level records. Figure 2 red components are source-display observations. Its time scale is hours, clarified by the later published Figure 2; preprint digitization and later unit clarification have distinct provenance. No simulation bands, bootstrap draws or residual arrays are reconstructed.","Adult IBD source context does not establish pediatric, infant or neonatal support. Fitting, individual dose recommendations and population prediction are unavailable.","Changing a simulation start applies the supplied initial state there; it does not reconstruct earlier administrations."],"name":"Berends rounded reference: SC induction and every 2 weeks","outputs":[{"classification":"provisional","description":"Model serum adalimumab concentration; conditional structural calculation.","key":"central_conc_mg_l","label":"Model serum adalimumab concentration","unit":"mg/L"},{"classification":"provisional","description":"Accumulated model exposure; conditional structural calculation.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"}],"scenario_id":"berends_adalimumab_induction_q2w_ode","scientific_questions":["How do the model's key biological readouts change under berends rounded reference: sc induction and every 2 weeks?"],"time_span":{"end":182,"start":0,"step":1}},{"controls":[],"description":"Fixed rounded Supplementary Table 1 CL/F, V/F and ka; no covariate, population or individual fit recalculation.","interpretation_guardrails":["The six rounded Table 1 probes remain fixed reference calculations. Six separate conditional variants add source-specific fixed covariate effects; no original population fit, random effects, residual likelihood, individual prediction or external-validation rankings are recalculated.","Berends, Marquez, Sanchez and Ternant variants use original fixed-effect sources. FDA uses the validation supplement equation; Vande uses original abstract structural estimates with validation-supplement covariate effects. Full original regulatory/Vande covariate and statistical verification is unavailable.","All covariates remain constant within each simulation. Original longitudinal covariate histories and patient-level dosing are not reconstructed. The shared nominal comparison regimen is not an individual or original-cohort regimen.","Binary source categories must be 0 or 1. The preset fixes model selection. Exploratory control bounds are not clinical validation ranges; marginal source ranges do not reconstruct joint patient records.","The apparent-parameter F=1 convention does not identify absolute bioavailability or true absorbed systemic mass. No separate bioavailability control is supplied.","Nominal dosing is 160 mg SC at day 0, 80 mg at day 14, then 40 mg every 14 days through day 182. The retained simulation grid uses post-dose at day 0 and pre-dose on later administration days, including day 182. Clinical source samples were collected before the corresponding dose; this simulation convention is not a patient sampling claim.","Dose input jumps the SC depot; central concentration, accumulated AUC and eliminated apparent amount remain continuous at a bolus.","Published cohort, parameter and performance values are fixed source references, not patient predictions or recalculated goodness-of-fit metrics.","Seven retained source-reference identities carry constants only. Their carrier clock is not a paper figure axis or clinical follow-up time; they must be shown as reference views outside the prediction interface.","Figure 1 digitized components are raster approximations, not patient-level records. Figure 2 red components are source-display observations. Its time scale is hours, clarified by the later published Figure 2; preprint digitization and later unit clarification have distinct provenance. No simulation bands, bootstrap draws or residual arrays are reconstructed.","Adult IBD source context does not establish pediatric, infant or neonatal support. Fitting, individual dose recommendations and population prediction are unavailable.","Changing a simulation start applies the supplied initial state there; it does not reconstruct earlier administrations."],"name":"FDA rounded reference: SC induction and every 2 weeks","outputs":[{"classification":"provisional","description":"Model serum adalimumab concentration; conditional structural calculation.","key":"central_conc_mg_l","label":"Model serum adalimumab concentration","unit":"mg/L"},{"classification":"provisional","description":"Accumulated model exposure; conditional structural calculation.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"}],"scenario_id":"fda_adalimumab_induction_q2w_ode","scientific_questions":["How do the model's key biological readouts change under fda rounded reference: sc induction and every 2 weeks?"],"time_span":{"end":182,"start":0,"step":1}},{"controls":[],"description":"Fixed rounded Supplementary Table 1 CL/F, V/F and ka; no covariate, population or individual fit recalculation.","interpretation_guardrails":["The six rounded Table 1 probes remain fixed reference calculations. Six separate conditional variants add source-specific fixed covariate effects; no original population fit, random effects, residual likelihood, individual prediction or external-validation rankings are recalculated.","Berends, Marquez, Sanchez and Ternant variants use original fixed-effect sources. FDA uses the validation supplement equation; Vande uses original abstract structural estimates with validation-supplement covariate effects. Full original regulatory/Vande covariate and statistical verification is unavailable.","All covariates remain constant within each simulation. Original longitudinal covariate histories and patient-level dosing are not reconstructed. The shared nominal comparison regimen is not an individual or original-cohort regimen.","Binary source categories must be 0 or 1. The preset fixes model selection. Exploratory control bounds are not clinical validation ranges; marginal source ranges do not reconstruct joint patient records.","The apparent-parameter F=1 convention does not identify absolute bioavailability or true absorbed systemic mass. No separate bioavailability control is supplied.","Nominal dosing is 160 mg SC at day 0, 80 mg at day 14, then 40 mg every 14 days through day 182. The retained simulation grid uses post-dose at day 0 and pre-dose on later administration days, including day 182. Clinical source samples were collected before the corresponding dose; this simulation convention is not a patient sampling claim.","Dose input jumps the SC depot; central concentration, accumulated AUC and eliminated apparent amount remain continuous at a bolus.","Published cohort, parameter and performance values are fixed source references, not patient predictions or recalculated goodness-of-fit metrics.","Seven retained source-reference identities carry constants only. Their carrier clock is not a paper figure axis or clinical follow-up time; they must be shown as reference views outside the prediction interface.","Figure 1 digitized components are raster approximations, not patient-level records. Figure 2 red components are source-display observations. Its time scale is hours, clarified by the later published Figure 2; preprint digitization and later unit clarification have distinct provenance. No simulation bands, bootstrap draws or residual arrays are reconstructed.","Adult IBD source context does not establish pediatric, infant or neonatal support. Fitting, individual dose recommendations and population prediction are unavailable.","Changing a simulation start applies the supplied initial state there; it does not reconstruct earlier administrations."],"name":"Marquez rounded reference: SC induction and every 2 weeks","outputs":[{"classification":"provisional","description":"Model serum adalimumab concentration; conditional structural calculation.","key":"central_conc_mg_l","label":"Model serum adalimumab concentration","unit":"mg/L"},{"classification":"provisional","description":"Accumulated model exposure; conditional structural calculation.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"}],"scenario_id":"marquez_adalimumab_induction_q2w_ode","scientific_questions":["How do the model's key biological readouts change under marquez rounded reference: sc induction and every 2 weeks?"],"time_span":{"end":182,"start":0,"step":1}},{"controls":[],"description":"Fixed rounded Supplementary Table 1 CL/F, V/F and ka; no covariate, population or individual fit recalculation.","interpretation_guardrails":["The six rounded Table 1 probes remain fixed reference calculations. Six separate conditional variants add source-specific fixed covariate effects; no original population fit, random effects, residual likelihood, individual prediction or external-validation rankings are recalculated.","Berends, Marquez, Sanchez and Ternant variants use original fixed-effect sources. FDA uses the validation supplement equation; Vande uses original abstract structural estimates with validation-supplement covariate effects. Full original regulatory/Vande covariate and statistical verification is unavailable.","All covariates remain constant within each simulation. Original longitudinal covariate histories and patient-level dosing are not reconstructed. The shared nominal comparison regimen is not an individual or original-cohort regimen.","Binary source categories must be 0 or 1. The preset fixes model selection. Exploratory control bounds are not clinical validation ranges; marginal source ranges do not reconstruct joint patient records.","The apparent-parameter F=1 convention does not identify absolute bioavailability or true absorbed systemic mass. No separate bioavailability control is supplied.","Nominal dosing is 160 mg SC at day 0, 80 mg at day 14, then 40 mg every 14 days through day 182. The retained simulation grid uses post-dose at day 0 and pre-dose on later administration days, including day 182. Clinical source samples were collected before the corresponding dose; this simulation convention is not a patient sampling claim.","Dose input jumps the SC depot; central concentration, accumulated AUC and eliminated apparent amount remain continuous at a bolus.","Published cohort, parameter and performance values are fixed source references, not patient predictions or recalculated goodness-of-fit metrics.","Seven retained source-reference identities carry constants only. Their carrier clock is not a paper figure axis or clinical follow-up time; they must be shown as reference views outside the prediction interface.","Figure 1 digitized components are raster approximations, not patient-level records. Figure 2 red components are source-display observations. Its time scale is hours, clarified by the later published Figure 2; preprint digitization and later unit clarification have distinct provenance. No simulation bands, bootstrap draws or residual arrays are reconstructed.","Adult IBD source context does not establish pediatric, infant or neonatal support. Fitting, individual dose recommendations and population prediction are unavailable.","Changing a simulation start applies the supplied initial state there; it does not reconstruct earlier administrations."],"name":"Sanchez rounded reference: SC induction and every 2 weeks","outputs":[{"classification":"provisional","description":"Model serum adalimumab concentration; conditional structural calculation.","key":"central_conc_mg_l","label":"Model serum adalimumab concentration","unit":"mg/L"},{"classification":"provisional","description":"Accumulated model exposure; conditional structural calculation.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"}],"scenario_id":"sanchez_adalimumab_induction_q2w_ode","scientific_questions":["How do the model's key biological readouts change under sanchez rounded reference: sc induction and every 2 weeks?"],"time_span":{"end":182,"start":0,"step":1}},{"controls":[],"description":"Fixed rounded Supplementary Table 1 CL/F, V/F and ka; no covariate, population or individual fit recalculation.","interpretation_guardrails":["The six rounded Table 1 probes remain fixed reference calculations. Six separate conditional variants add source-specific fixed covariate effects; no original population fit, random effects, residual likelihood, individual prediction or external-validation rankings are recalculated.","Berends, Marquez, Sanchez and Ternant variants use original fixed-effect sources. FDA uses the validation supplement equation; Vande uses original abstract structural estimates with validation-supplement covariate effects. Full original regulatory/Vande covariate and statistical verification is unavailable.","All covariates remain constant within each simulation. Original longitudinal covariate histories and patient-level dosing are not reconstructed. The shared nominal comparison regimen is not an individual or original-cohort regimen.","Binary source categories must be 0 or 1. The preset fixes model selection. Exploratory control bounds are not clinical validation ranges; marginal source ranges do not reconstruct joint patient records.","The apparent-parameter F=1 convention does not identify absolute bioavailability or true absorbed systemic mass. No separate bioavailability control is supplied.","Nominal dosing is 160 mg SC at day 0, 80 mg at day 14, then 40 mg every 14 days through day 182. The retained simulation grid uses post-dose at day 0 and pre-dose on later administration days, including day 182. Clinical source samples were collected before the corresponding dose; this simulation convention is not a patient sampling claim.","Dose input jumps the SC depot; central concentration, accumulated AUC and eliminated apparent amount remain continuous at a bolus.","Published cohort, parameter and performance values are fixed source references, not patient predictions or recalculated goodness-of-fit metrics.","Seven retained source-reference identities carry constants only. Their carrier clock is not a paper figure axis or clinical follow-up time; they must be shown as reference views outside the prediction interface.","Figure 1 digitized components are raster approximations, not patient-level records. Figure 2 red components are source-display observations. Its time scale is hours, clarified by the later published Figure 2; preprint digitization and later unit clarification have distinct provenance. No simulation bands, bootstrap draws or residual arrays are reconstructed.","Adult IBD source context does not establish pediatric, infant or neonatal support. Fitting, individual dose recommendations and population prediction are unavailable.","Changing a simulation start applies the supplied initial state there; it does not reconstruct earlier administrations."],"name":"Ternant rounded reference: SC induction and every 2 weeks","outputs":[{"classification":"provisional","description":"Model serum adalimumab concentration; conditional structural calculation.","key":"central_conc_mg_l","label":"Model serum adalimumab concentration","unit":"mg/L"},{"classification":"provisional","description":"Accumulated model exposure; conditional structural calculation.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"}],"scenario_id":"ternant_adalimumab_induction_q2w_ode","scientific_questions":["How do the model's key biological readouts change under ternant rounded reference: sc induction and every 2 weeks?"],"time_span":{"end":182,"start":0,"step":1}},{"controls":[],"description":"Fixed rounded Supplementary Table 1 CL/F, V/F and ka; no covariate, population or individual fit recalculation.","interpretation_guardrails":["The six rounded Table 1 probes remain fixed reference calculations. Six separate conditional variants add source-specific fixed covariate effects; no original population fit, random effects, residual likelihood, individual prediction or external-validation rankings are recalculated.","Berends, Marquez, Sanchez and Ternant variants use original fixed-effect sources. FDA uses the validation supplement equation; Vande uses original abstract structural estimates with validation-supplement covariate effects. Full original regulatory/Vande covariate and statistical verification is unavailable.","All covariates remain constant within each simulation. Original longitudinal covariate histories and patient-level dosing are not reconstructed. The shared nominal comparison regimen is not an individual or original-cohort regimen.","Binary source categories must be 0 or 1. The preset fixes model selection. Exploratory control bounds are not clinical validation ranges; marginal source ranges do not reconstruct joint patient records.","The apparent-parameter F=1 convention does not identify absolute bioavailability or true absorbed systemic mass. No separate bioavailability control is supplied.","Nominal dosing is 160 mg SC at day 0, 80 mg at day 14, then 40 mg every 14 days through day 182. The retained simulation grid uses post-dose at day 0 and pre-dose on later administration days, including day 182. Clinical source samples were collected before the corresponding dose; this simulation convention is not a patient sampling claim.","Dose input jumps the SC depot; central concentration, accumulated AUC and eliminated apparent amount remain continuous at a bolus.","Published cohort, parameter and performance values are fixed source references, not patient predictions or recalculated goodness-of-fit metrics.","Seven retained source-reference identities carry constants only. Their carrier clock is not a paper figure axis or clinical follow-up time; they must be shown as reference views outside the prediction interface.","Figure 1 digitized components are raster approximations, not patient-level records. Figure 2 red components are source-display observations. Its time scale is hours, clarified by the later published Figure 2; preprint digitization and later unit clarification have distinct provenance. No simulation bands, bootstrap draws or residual arrays are reconstructed.","Adult IBD source context does not establish pediatric, infant or neonatal support. Fitting, individual dose recommendations and population prediction are unavailable.","Changing a simulation start applies the supplied initial state there; it does not reconstruct earlier administrations."],"name":"Vande rounded reference: SC induction and every 2 weeks","outputs":[{"classification":"provisional","description":"Model serum adalimumab concentration; conditional structural calculation.","key":"central_conc_mg_l","label":"Model serum adalimumab concentration","unit":"mg/L"},{"classification":"provisional","description":"Accumulated model exposure; conditional structural calculation.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"}],"scenario_id":"vande_adalimumab_induction_q2w_ode","scientific_questions":["How do the model's key biological readouts change under vande rounded reference: sc induction and every 2 weeks?"],"time_span":{"end":182,"start":0,"step":1}},{"controls":[{"allowed_values":[0,1],"category":"Conditional source covariate","definition":"Source-specific binary negative/positive category, not antibody titer; assay definitions vary by study.","description":"Source-specific binary negative/positive category, not antibody titer; assay definitions vary by study.","key":"aaa_positive","label":"Anti adalimumab antibody category","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Source-specific binary negative/positive category, not antibody titer; assay definitions vary by study.","step":0.01,"unit":"1","value":0},{"allowed_values":[0,1],"category":"Conditional source covariate","definition":"Berends observational weekly versus every-other-week category; editing this category does not change administrations and does not imply a causal dosing effect on clearance.","description":"Berends observational weekly versus every-other-week category; editing this category does not change administrations and does not imply a causal dosing effect on clearance.","key":"observed_weekly_category","label":"Observed weekly dosing category","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Berends observational weekly versus every-other-week category; editing this category does not change administrations and does not imply a causal dosing effect on clearance.","step":0.01,"unit":"1","value":0}],"description":"Original Berends2018 conditional fixed effects; observed dosing category is associative. No random effects or mixed residual model. Uses the common nominal160/80/40mg SC comparison regimen, not reconstructed patient dosing.","interpretation_guardrails":["The six rounded Table 1 probes remain fixed reference calculations. Six separate conditional variants add source-specific fixed covariate effects; no original population fit, random effects, residual likelihood, individual prediction or external-validation rankings are recalculated.","Berends, Marquez, Sanchez and Ternant variants use original fixed-effect sources. FDA uses the validation supplement equation; Vande uses original abstract structural estimates with validation-supplement covariate effects. Full original regulatory/Vande covariate and statistical verification is unavailable.","All covariates remain constant within each simulation. Original longitudinal covariate histories and patient-level dosing are not reconstructed. The shared nominal comparison regimen is not an individual or original-cohort regimen.","Binary source categories must be 0 or 1. The preset fixes model selection. Exploratory control bounds are not clinical validation ranges; marginal source ranges do not reconstruct joint patient records.","The apparent-parameter F=1 convention does not identify absolute bioavailability or true absorbed systemic mass. No separate bioavailability control is supplied.","Nominal dosing is 160 mg SC at day 0, 80 mg at day 14, then 40 mg every 14 days through day 182. The retained simulation grid uses post-dose at day 0 and pre-dose on later administration days, including day 182. Clinical source samples were collected before the corresponding dose; this simulation convention is not a patient sampling claim.","Dose input jumps the SC depot; central concentration, accumulated AUC and eliminated apparent amount remain continuous at a bolus.","Published cohort, parameter and performance values are fixed source references, not patient predictions or recalculated goodness-of-fit metrics.","Seven retained source-reference identities carry constants only. Their carrier clock is not a paper figure axis or clinical follow-up time; they must be shown as reference views outside the prediction interface.","Figure 1 digitized components are raster approximations, not patient-level records. Figure 2 red components are source-display observations. Its time scale is hours, clarified by the later published Figure 2; preprint digitization and later unit clarification have distinct provenance. No simulation bands, bootstrap draws or residual arrays are reconstructed.","Adult IBD source context does not establish pediatric, infant or neonatal support. Fitting, individual dose recommendations and population prediction are unavailable.","Changing a simulation start applies the supplied initial state there; it does not reconstruct earlier administrations."],"name":"Berends original fixed effects","outputs":[{"classification":"provisional","description":"Model serum adalimumab concentration; conditional structural calculation.","key":"central_conc_mg_l","label":"Model serum adalimumab concentration","unit":"mg/L"},{"classification":"provisional","description":"Accumulated model exposure; conditional structural calculation.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"}],"scenario_id":"berends_conditional_fixed_effect_induction_q2w","scientific_questions":["How do source-specific fixed covariate effects change conditional adalimumab exposure?"],"time_span":{"end":182,"start":0,"step":1}},{"controls":[{"category":"Conditional source covariate","definition":"FDA SI projection: exploratory adult input bounds, not a verified regulatory validation domain.","description":"FDA SI projection: exploratory adult input bounds, not a verified regulatory validation domain.","key":"body_weight_kg","label":"Body weight","max":100,"min":50,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"FDA SI projection: exploratory adult input bounds, not a verified regulatory validation domain.","step":0.1,"unit":"kg","value":72}],"description":"Conditional FDA equation reported in the external-validation supplement. Original regulatory domain and statistical model independently unverified. Uses the common nominal160/80/40mg SC comparison regimen, not reconstructed patient dosing.","interpretation_guardrails":["The six rounded Table 1 probes remain fixed reference calculations. Six separate conditional variants add source-specific fixed covariate effects; no original population fit, random effects, residual likelihood, individual prediction or external-validation rankings are recalculated.","Berends, Marquez, Sanchez and Ternant variants use original fixed-effect sources. FDA uses the validation supplement equation; Vande uses original abstract structural estimates with validation-supplement covariate effects. Full original regulatory/Vande covariate and statistical verification is unavailable.","All covariates remain constant within each simulation. Original longitudinal covariate histories and patient-level dosing are not reconstructed. The shared nominal comparison regimen is not an individual or original-cohort regimen.","Binary source categories must be 0 or 1. The preset fixes model selection. Exploratory control bounds are not clinical validation ranges; marginal source ranges do not reconstruct joint patient records.","The apparent-parameter F=1 convention does not identify absolute bioavailability or true absorbed systemic mass. No separate bioavailability control is supplied.","Nominal dosing is 160 mg SC at day 0, 80 mg at day 14, then 40 mg every 14 days through day 182. The retained simulation grid uses post-dose at day 0 and pre-dose on later administration days, including day 182. Clinical source samples were collected before the corresponding dose; this simulation convention is not a patient sampling claim.","Dose input jumps the SC depot; central concentration, accumulated AUC and eliminated apparent amount remain continuous at a bolus.","Published cohort, parameter and performance values are fixed source references, not patient predictions or recalculated goodness-of-fit metrics.","Seven retained source-reference identities carry constants only. Their carrier clock is not a paper figure axis or clinical follow-up time; they must be shown as reference views outside the prediction interface.","Figure 1 digitized components are raster approximations, not patient-level records. Figure 2 red components are source-display observations. Its time scale is hours, clarified by the later published Figure 2; preprint digitization and later unit clarification have distinct provenance. No simulation bands, bootstrap draws or residual arrays are reconstructed.","Adult IBD source context does not establish pediatric, infant or neonatal support. Fitting, individual dose recommendations and population prediction are unavailable.","Changing a simulation start applies the supplied initial state there; it does not reconstruct earlier administrations."],"name":"FDA supplement projection","outputs":[{"classification":"provisional","description":"Model serum adalimumab concentration; conditional structural calculation.","key":"central_conc_mg_l","label":"Model serum adalimumab concentration","unit":"mg/L"},{"classification":"provisional","description":"Accumulated model exposure; conditional structural calculation.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"}],"scenario_id":"fda_conditional_fixed_effect_induction_q2w","scientific_questions":["How do source-specific fixed covariate effects change conditional adalimumab exposure?"],"time_span":{"end":182,"start":0,"step":1}},{"controls":[{"allowed_values":[0,1],"category":"Conditional source covariate","definition":"Source-specific binary negative/positive category, not antibody titer; assay definitions vary by study.","description":"Source-specific binary negative/positive category, not antibody titer; assay definitions vary by study.","key":"aaa_positive","label":"Anti adalimumab antibody category","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Source-specific binary negative/positive category, not antibody titer; assay definitions vary by study.","step":0.01,"unit":"1","value":0},{"category":"Conditional source covariate","definition":"Marquez source range19.7–49.6g/L; mean normalization37.7g/L. Held constant in each projection; original regressor was time varying.","description":"Marquez source range19.7–49.6g/L; mean normalization37.7g/L. Held constant in each projection; original regressor was time varying.","key":"albumin_g_l","label":"Albumin","max":49.6,"min":19.7,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Marquez source range19.7–49.6g/L; mean normalization37.7g/L. Held constant in each projection; original regressor was time varying.","step":0.1,"unit":"g/L","value":37.7}],"description":"Original Marquez2023 fixed effects with source albumin normalization and AAA category. Albumin is held constant; original covariate histories, informative priors and fit are absent. Uses the common nominal160/80/40mg SC comparison regimen, not reconstructed patient dosing.","interpretation_guardrails":["The six rounded Table 1 probes remain fixed reference calculations. Six separate conditional variants add source-specific fixed covariate effects; no original population fit, random effects, residual likelihood, individual prediction or external-validation rankings are recalculated.","Berends, Marquez, Sanchez and Ternant variants use original fixed-effect sources. FDA uses the validation supplement equation; Vande uses original abstract structural estimates with validation-supplement covariate effects. Full original regulatory/Vande covariate and statistical verification is unavailable.","All covariates remain constant within each simulation. Original longitudinal covariate histories and patient-level dosing are not reconstructed. The shared nominal comparison regimen is not an individual or original-cohort regimen.","Binary source categories must be 0 or 1. The preset fixes model selection. Exploratory control bounds are not clinical validation ranges; marginal source ranges do not reconstruct joint patient records.","The apparent-parameter F=1 convention does not identify absolute bioavailability or true absorbed systemic mass. No separate bioavailability control is supplied.","Nominal dosing is 160 mg SC at day 0, 80 mg at day 14, then 40 mg every 14 days through day 182. The retained simulation grid uses post-dose at day 0 and pre-dose on later administration days, including day 182. Clinical source samples were collected before the corresponding dose; this simulation convention is not a patient sampling claim.","Dose input jumps the SC depot; central concentration, accumulated AUC and eliminated apparent amount remain continuous at a bolus.","Published cohort, parameter and performance values are fixed source references, not patient predictions or recalculated goodness-of-fit metrics.","Seven retained source-reference identities carry constants only. Their carrier clock is not a paper figure axis or clinical follow-up time; they must be shown as reference views outside the prediction interface.","Figure 1 digitized components are raster approximations, not patient-level records. Figure 2 red components are source-display observations. Its time scale is hours, clarified by the later published Figure 2; preprint digitization and later unit clarification have distinct provenance. No simulation bands, bootstrap draws or residual arrays are reconstructed.","Adult IBD source context does not establish pediatric, infant or neonatal support. Fitting, individual dose recommendations and population prediction are unavailable.","Changing a simulation start applies the supplied initial state there; it does not reconstruct earlier administrations."],"name":"Marquez original fixed effects","outputs":[{"classification":"provisional","description":"Model serum adalimumab concentration; conditional structural calculation.","key":"central_conc_mg_l","label":"Model serum adalimumab concentration","unit":"mg/L"},{"classification":"provisional","description":"Accumulated model exposure; conditional structural calculation.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"}],"scenario_id":"marquez_conditional_fixed_effect_induction_q2w","scientific_questions":["How do source-specific fixed covariate effects change conditional adalimumab exposure?"],"time_span":{"end":182,"start":0,"step":1}},{"controls":[{"category":"Conditional source covariate","definition":"Exploratory bounds; source illustrated20/23.7/30kg/m². The80mg-pen effect applies only at BMI>=20.","description":"Exploratory bounds; source illustrated20/23.7/30kg/m². The80mg-pen effect applies only at BMI>=20.","key":"bmi_kg_m2","label":"Body mass index","max":35,"min":18,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Exploratory bounds; source illustrated20/23.7/30kg/m². The80mg-pen effect applies only at BMI>=20.","step":0.1,"unit":"kg/m^2","value":23.7},{"category":"Conditional source covariate","definition":"Strictly positive mg/kg, numerically identical to µg/g. Source illustrated5/100/200/500; these are exploratory levels, not a validated clinical range.","description":"Strictly positive mg/kg, numerically identical to µg/g. Source illustrated5/100/200/500; these are exploratory levels, not a validated clinical range.","key":"fecal_calprotectin_mg_kg","label":"Fecal calprotectin","max":500,"min":5,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Strictly positive mg/kg, numerically identical to µg/g. Source illustrated5/100/200/500; these are exploratory levels, not a validated clinical range.","step":0.1,"unit":"mg/kg","value":74},{"allowed_values":[0,1],"category":"Conditional source covariate","definition":"Sanchez maintenance category: >=33%ASC decrease despite confirmed adherence, no dose change or inflammatory worsening, reversible with intensification. It is not an AAA proxy.","description":"Sanchez maintenance category: >=33%ASC decrease despite confirmed adherence, no dose change or inflammatory worsening, reversible with intensification. It is not an AAA proxy.","key":"unexplained_asc_decrease","label":"Source defined unexplained concentration decrease","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Sanchez maintenance category: >=33%ASC decrease despite confirmed adherence, no dose change or inflammatory worsening, reversible with intensification. It is not an AAA proxy.","step":0.01,"unit":"1","value":0},{"allowed_values":[0,1],"category":"Conditional source covariate","definition":"Source device category, not prescribed dose amount. Two40mg administrations are not this category.","description":"Source device category, not prescribed dose amount. Two40mg administrations are not this category.","key":"pen_80mg_category","label":"80mg pen category","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Source device category, not prescribed dose amount. Two40mg administrations are not this category.","step":0.01,"unit":"1","value":0}],"description":"Original Sanchez2020 Table3 estimates and BMI-dependent device category; source-defined unexplained concentration decrease is separate from AAA. Uses the common nominal160/80/40mg SC comparison regimen, not reconstructed patient dosing.","interpretation_guardrails":["The six rounded Table 1 probes remain fixed reference calculations. Six separate conditional variants add source-specific fixed covariate effects; no original population fit, random effects, residual likelihood, individual prediction or external-validation rankings are recalculated.","Berends, Marquez, Sanchez and Ternant variants use original fixed-effect sources. FDA uses the validation supplement equation; Vande uses original abstract structural estimates with validation-supplement covariate effects. Full original regulatory/Vande covariate and statistical verification is unavailable.","All covariates remain constant within each simulation. Original longitudinal covariate histories and patient-level dosing are not reconstructed. The shared nominal comparison regimen is not an individual or original-cohort regimen.","Binary source categories must be 0 or 1. The preset fixes model selection. Exploratory control bounds are not clinical validation ranges; marginal source ranges do not reconstruct joint patient records.","The apparent-parameter F=1 convention does not identify absolute bioavailability or true absorbed systemic mass. No separate bioavailability control is supplied.","Nominal dosing is 160 mg SC at day 0, 80 mg at day 14, then 40 mg every 14 days through day 182. The retained simulation grid uses post-dose at day 0 and pre-dose on later administration days, including day 182. Clinical source samples were collected before the corresponding dose; this simulation convention is not a patient sampling claim.","Dose input jumps the SC depot; central concentration, accumulated AUC and eliminated apparent amount remain continuous at a bolus.","Published cohort, parameter and performance values are fixed source references, not patient predictions or recalculated goodness-of-fit metrics.","Seven retained source-reference identities carry constants only. Their carrier clock is not a paper figure axis or clinical follow-up time; they must be shown as reference views outside the prediction interface.","Figure 1 digitized components are raster approximations, not patient-level records. Figure 2 red components are source-display observations. Its time scale is hours, clarified by the later published Figure 2; preprint digitization and later unit clarification have distinct provenance. No simulation bands, bootstrap draws or residual arrays are reconstructed.","Adult IBD source context does not establish pediatric, infant or neonatal support. Fitting, individual dose recommendations and population prediction are unavailable.","Changing a simulation start applies the supplied initial state there; it does not reconstruct earlier administrations."],"name":"Sanchez original fixed effects","outputs":[{"classification":"provisional","description":"Model serum adalimumab concentration; conditional structural calculation.","key":"central_conc_mg_l","label":"Model serum adalimumab concentration","unit":"mg/L"},{"classification":"provisional","description":"Accumulated model exposure; conditional structural calculation.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"}],"scenario_id":"sanchez_conditional_fixed_effect_induction_q2w","scientific_questions":["How do source-specific fixed covariate effects change conditional adalimumab exposure?"],"time_span":{"end":182,"start":0,"step":1}},{"controls":[{"allowed_values":[0,1],"category":"Conditional source covariate","definition":"Source-specific binary negative/positive category, not antibody titer; assay definitions vary by study.","description":"Source-specific binary negative/positive category, not antibody titer; assay definitions vary by study.","key":"aaa_positive","label":"Anti adalimumab antibody category","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Source-specific binary negative/positive category, not antibody titer; assay definitions vary by study.","step":0.01,"unit":"1","value":0}],"description":"Original Ternant2015 Crohn disease fixed effects; no variability, mixed residual model or individual fit. Uses the common nominal160/80/40mg SC comparison regimen, not reconstructed patient dosing.","interpretation_guardrails":["The six rounded Table 1 probes remain fixed reference calculations. Six separate conditional variants add source-specific fixed covariate effects; no original population fit, random effects, residual likelihood, individual prediction or external-validation rankings are recalculated.","Berends, Marquez, Sanchez and Ternant variants use original fixed-effect sources. FDA uses the validation supplement equation; Vande uses original abstract structural estimates with validation-supplement covariate effects. Full original regulatory/Vande covariate and statistical verification is unavailable.","All covariates remain constant within each simulation. Original longitudinal covariate histories and patient-level dosing are not reconstructed. The shared nominal comparison regimen is not an individual or original-cohort regimen.","Binary source categories must be 0 or 1. The preset fixes model selection. Exploratory control bounds are not clinical validation ranges; marginal source ranges do not reconstruct joint patient records.","The apparent-parameter F=1 convention does not identify absolute bioavailability or true absorbed systemic mass. No separate bioavailability control is supplied.","Nominal dosing is 160 mg SC at day 0, 80 mg at day 14, then 40 mg every 14 days through day 182. The retained simulation grid uses post-dose at day 0 and pre-dose on later administration days, including day 182. Clinical source samples were collected before the corresponding dose; this simulation convention is not a patient sampling claim.","Dose input jumps the SC depot; central concentration, accumulated AUC and eliminated apparent amount remain continuous at a bolus.","Published cohort, parameter and performance values are fixed source references, not patient predictions or recalculated goodness-of-fit metrics.","Seven retained source-reference identities carry constants only. Their carrier clock is not a paper figure axis or clinical follow-up time; they must be shown as reference views outside the prediction interface.","Figure 1 digitized components are raster approximations, not patient-level records. Figure 2 red components are source-display observations. Its time scale is hours, clarified by the later published Figure 2; preprint digitization and later unit clarification have distinct provenance. No simulation bands, bootstrap draws or residual arrays are reconstructed.","Adult IBD source context does not establish pediatric, infant or neonatal support. Fitting, individual dose recommendations and population prediction are unavailable.","Changing a simulation start applies the supplied initial state there; it does not reconstruct earlier administrations."],"name":"Ternant original fixed effects","outputs":[{"classification":"provisional","description":"Model serum adalimumab concentration; conditional structural calculation.","key":"central_conc_mg_l","label":"Model serum adalimumab concentration","unit":"mg/L"},{"classification":"provisional","description":"Accumulated model exposure; conditional structural calculation.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"}],"scenario_id":"ternant_conditional_fixed_effect_induction_q2w","scientific_questions":["How do source-specific fixed covariate effects change conditional adalimumab exposure?"],"time_span":{"end":182,"start":0,"step":1}},{"controls":[{"allowed_values":[0,1],"category":"Conditional source covariate","definition":"Source-specific binary negative/positive category, not antibody titer; assay definitions vary by study.","description":"Source-specific binary negative/positive category, not antibody titer; assay definitions vary by study.","key":"aaa_positive","label":"Anti adalimumab antibody category","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Source-specific binary negative/positive category, not antibody titer; assay definitions vary by study.","step":0.01,"unit":"1","value":0},{"category":"Conditional source covariate","definition":"Direct exploratory LBW input; no unverified height/weight/sex formula. Bounds are not a validated source domain.","description":"Direct exploratory LBW input; no unverified height/weight/sex formula. Bounds are not a validated source domain.","key":"lean_body_weight_kg","label":"Lean body weight","max":65,"min":35,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Direct exploratory LBW input; no unverified height/weight/sex formula. Bounds are not a validated source domain.","step":0.1,"unit":"kg","value":47.81}],"description":"Original Vande abstract structural estimates with validation-supplement AAA/LBW effects. Full original covariate and statistical model independently unverified. Uses the common nominal160/80/40mg SC comparison regimen, not reconstructed patient dosing.","interpretation_guardrails":["The six rounded Table 1 probes remain fixed reference calculations. Six separate conditional variants add source-specific fixed covariate effects; no original population fit, random effects, residual likelihood, individual prediction or external-validation rankings are recalculated.","Berends, Marquez, Sanchez and Ternant variants use original fixed-effect sources. FDA uses the validation supplement equation; Vande uses original abstract structural estimates with validation-supplement covariate effects. Full original regulatory/Vande covariate and statistical verification is unavailable.","All covariates remain constant within each simulation. Original longitudinal covariate histories and patient-level dosing are not reconstructed. The shared nominal comparison regimen is not an individual or original-cohort regimen.","Binary source categories must be 0 or 1. The preset fixes model selection. Exploratory control bounds are not clinical validation ranges; marginal source ranges do not reconstruct joint patient records.","The apparent-parameter F=1 convention does not identify absolute bioavailability or true absorbed systemic mass. No separate bioavailability control is supplied.","Nominal dosing is 160 mg SC at day 0, 80 mg at day 14, then 40 mg every 14 days through day 182. The retained simulation grid uses post-dose at day 0 and pre-dose on later administration days, including day 182. Clinical source samples were collected before the corresponding dose; this simulation convention is not a patient sampling claim.","Dose input jumps the SC depot; central concentration, accumulated AUC and eliminated apparent amount remain continuous at a bolus.","Published cohort, parameter and performance values are fixed source references, not patient predictions or recalculated goodness-of-fit metrics.","Seven retained source-reference identities carry constants only. Their carrier clock is not a paper figure axis or clinical follow-up time; they must be shown as reference views outside the prediction interface.","Figure 1 digitized components are raster approximations, not patient-level records. Figure 2 red components are source-display observations. Its time scale is hours, clarified by the later published Figure 2; preprint digitization and later unit clarification have distinct provenance. No simulation bands, bootstrap draws or residual arrays are reconstructed.","Adult IBD source context does not establish pediatric, infant or neonatal support. Fitting, individual dose recommendations and population prediction are unavailable.","Changing a simulation start applies the supplied initial state there; it does not reconstruct earlier administrations."],"name":"Vande supplement projection","outputs":[{"classification":"provisional","description":"Model serum adalimumab concentration; conditional structural calculation.","key":"central_conc_mg_l","label":"Model serum adalimumab concentration","unit":"mg/L"},{"classification":"provisional","description":"Accumulated model exposure; conditional structural calculation.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"}],"scenario_id":"vande_conditional_fixed_effect_induction_q2w","scientific_questions":["How do source-specific fixed covariate effects change conditional adalimumab exposure?"],"time_span":{"end":182,"start":0,"step":1}}],"targets":[{"key":"tnf","label":"TNF / TNFA"}],"therapeutics":[{"key":"adalimumab","label":"Adalimumab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.1.0"},{"availability":{"catalog_qualified":true,"released":true},"description":"Separate fixed two-compartment intact-ADC contexts with explicit exposure and drug accounting.","diseases":[{"key":"her2_positive_cancers","label":"HER2-positive cancers","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1002/psp4.70013","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"links":{"page":"/modeling/models/asiimwe-2025-adc-mbma-cui-poppk","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"Antibody-drug conjugate","model_classes":["Two-compartment PK","Fixed study context"],"model_id":"asiimwe_2025_adc_mbma_cui_poppk","name":"T-DM1 and T-DXd conditional intact-ADC pharmacokinetics","outputs":[{"description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"central_conc_ng_ml","label":"Central conc","unit":"ng/mL"},{"description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"auc_ng_day_ml","label":"Exposure (AUC)","unit":"ng*day/mL"},{"description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"accounted_adc_mg","label":"Accounted ADC","unit":"mg"},{"description":"Fixed-matrix slow-phase half-life; not a clinical population estimate.","key":"fixed_coefficient_terminal_half_life_day","label":"Fixed coefficient terminal half-life","unit":"day"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Single specified 90-minute infusion followed through day 21; fixed intact-ADC PK coefficients and zero log deviations.","interpretation_guardrails":["Deterministic fixed infusion histories only; no original meta-analysis fitting, sampled population, response prediction or clinical dose selection.","Intact ADC serum is the modeled analyte. The apparent peripheral pool is unmeasured; no receptor, payload or binding mechanism is represented.","T-DM1 and T-DXd use separate reported fixed PK coefficients. Fixed study-level log deviations remain zero in every preset; they are not sampled patient effects.","Reference body weight converts mg/kg to mg only; kinetic coefficients have no weight covariate.","AUC, elapsed day and eliminated amount are nonfeedback observers. Physical day-based AUC units remain unchanged under an hour display.","The terminal half-life readout belongs to the fixed two-compartment coefficient matrix, not a clinical population distribution."],"name":"T-DM1 0.3 mg/kg, fixed cycle-1 PK","outputs":[{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"central_conc_ng_ml","label":"Central conc","unit":"ng/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"auc_ng_day_ml","label":"Exposure (AUC)","unit":"ng*day/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"accounted_adc_mg","label":"Accounted ADC","unit":"mg"},{"classification":"provisional","description":"Fixed-matrix slow-phase half-life; not a clinical population estimate.","key":"fixed_coefficient_terminal_half_life_day","label":"Fixed coefficient terminal half-life","unit":"day"}],"scenario_id":"tdm1_0p3mgkg_cycle1_fixed_effect_ode","scientific_questions":["How do the model's key biological readouts change under t-dm1 0.3 mg/kg, fixed cycle-1 pk?"],"time_span":{"end":21,"start":0,"step":0.025}},{"controls":[],"description":"Single specified 90-minute infusion followed through day 21; fixed intact-ADC PK coefficients and zero log deviations.","interpretation_guardrails":["Deterministic fixed infusion histories only; no original meta-analysis fitting, sampled population, response prediction or clinical dose selection.","Intact ADC serum is the modeled analyte. The apparent peripheral pool is unmeasured; no receptor, payload or binding mechanism is represented.","T-DM1 and T-DXd use separate reported fixed PK coefficients. Fixed study-level log deviations remain zero in every preset; they are not sampled patient effects.","Reference body weight converts mg/kg to mg only; kinetic coefficients have no weight covariate.","AUC, elapsed day and eliminated amount are nonfeedback observers. Physical day-based AUC units remain unchanged under an hour display.","The terminal half-life readout belongs to the fixed two-compartment coefficient matrix, not a clinical population distribution."],"name":"T-DM1 0.6 mg/kg, fixed cycle-1 PK","outputs":[{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"central_conc_ng_ml","label":"Central conc","unit":"ng/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"auc_ng_day_ml","label":"Exposure (AUC)","unit":"ng*day/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"accounted_adc_mg","label":"Accounted ADC","unit":"mg"},{"classification":"provisional","description":"Fixed-matrix slow-phase half-life; not a clinical population estimate.","key":"fixed_coefficient_terminal_half_life_day","label":"Fixed coefficient terminal half-life","unit":"day"}],"scenario_id":"tdm1_0p6mgkg_cycle1_fixed_effect_ode","scientific_questions":["How do the model's key biological readouts change under t-dm1 0.6 mg/kg, fixed cycle-1 pk?"],"time_span":{"end":21,"start":0,"step":0.025}},{"controls":[],"description":"Single specified 90-minute infusion followed through day 21; fixed intact-ADC PK coefficients and zero log deviations.","interpretation_guardrails":["Deterministic fixed infusion histories only; no original meta-analysis fitting, sampled population, response prediction or clinical dose selection.","Intact ADC serum is the modeled analyte. The apparent peripheral pool is unmeasured; no receptor, payload or binding mechanism is represented.","T-DM1 and T-DXd use separate reported fixed PK coefficients. Fixed study-level log deviations remain zero in every preset; they are not sampled patient effects.","Reference body weight converts mg/kg to mg only; kinetic coefficients have no weight covariate.","AUC, elapsed day and eliminated amount are nonfeedback observers. Physical day-based AUC units remain unchanged under an hour display.","The terminal half-life readout belongs to the fixed two-compartment coefficient matrix, not a clinical population distribution."],"name":"T-DM1 1.2 mg/kg, fixed cycle-1 PK","outputs":[{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"central_conc_ng_ml","label":"Central conc","unit":"ng/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"auc_ng_day_ml","label":"Exposure (AUC)","unit":"ng*day/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"accounted_adc_mg","label":"Accounted ADC","unit":"mg"},{"classification":"provisional","description":"Fixed-matrix slow-phase half-life; not a clinical population estimate.","key":"fixed_coefficient_terminal_half_life_day","label":"Fixed coefficient terminal half-life","unit":"day"}],"scenario_id":"tdm1_1p2mgkg_cycle1_fixed_effect_ode","scientific_questions":["How do the model's key biological readouts change under t-dm1 1.2 mg/kg, fixed cycle-1 pk?"],"time_span":{"end":21,"start":0,"step":0.025}},{"controls":[],"description":"Single specified 90-minute infusion followed through day 21; fixed intact-ADC PK coefficients and zero log deviations.","interpretation_guardrails":["Deterministic fixed infusion histories only; no original meta-analysis fitting, sampled population, response prediction or clinical dose selection.","Intact ADC serum is the modeled analyte. The apparent peripheral pool is unmeasured; no receptor, payload or binding mechanism is represented.","T-DM1 and T-DXd use separate reported fixed PK coefficients. Fixed study-level log deviations remain zero in every preset; they are not sampled patient effects.","Reference body weight converts mg/kg to mg only; kinetic coefficients have no weight covariate.","AUC, elapsed day and eliminated amount are nonfeedback observers. Physical day-based AUC units remain unchanged under an hour display.","The terminal half-life readout belongs to the fixed two-compartment coefficient matrix, not a clinical population distribution."],"name":"T-DM1 1.8 mg/kg, fixed cycle-1 PK","outputs":[{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"central_conc_ng_ml","label":"Central conc","unit":"ng/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"auc_ng_day_ml","label":"Exposure (AUC)","unit":"ng*day/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"accounted_adc_mg","label":"Accounted ADC","unit":"mg"},{"classification":"provisional","description":"Fixed-matrix slow-phase half-life; not a clinical population estimate.","key":"fixed_coefficient_terminal_half_life_day","label":"Fixed coefficient terminal half-life","unit":"day"}],"scenario_id":"tdm1_1p8mgkg_cycle1_fixed_effect_ode","scientific_questions":["How do the model's key biological readouts change under t-dm1 1.8 mg/kg, fixed cycle-1 pk?"],"time_span":{"end":21,"start":0,"step":0.025}},{"controls":[],"description":"Single specified 90-minute infusion followed through day 21; fixed intact-ADC PK coefficients and zero log deviations.","interpretation_guardrails":["Deterministic fixed infusion histories only; no original meta-analysis fitting, sampled population, response prediction or clinical dose selection.","Intact ADC serum is the modeled analyte. The apparent peripheral pool is unmeasured; no receptor, payload or binding mechanism is represented.","T-DM1 and T-DXd use separate reported fixed PK coefficients. Fixed study-level log deviations remain zero in every preset; they are not sampled patient effects.","Reference body weight converts mg/kg to mg only; kinetic coefficients have no weight covariate.","AUC, elapsed day and eliminated amount are nonfeedback observers. Physical day-based AUC units remain unchanged under an hour display.","The terminal half-life readout belongs to the fixed two-compartment coefficient matrix, not a clinical population distribution."],"name":"T-DM1 2.4 mg/kg, fixed cycle-1 PK","outputs":[{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"central_conc_ng_ml","label":"Central conc","unit":"ng/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"auc_ng_day_ml","label":"Exposure (AUC)","unit":"ng*day/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"accounted_adc_mg","label":"Accounted ADC","unit":"mg"},{"classification":"provisional","description":"Fixed-matrix slow-phase half-life; not a clinical population estimate.","key":"fixed_coefficient_terminal_half_life_day","label":"Fixed coefficient terminal half-life","unit":"day"}],"scenario_id":"tdm1_2p4mgkg_cycle1_fixed_effect_ode","scientific_questions":["How do the model's key biological readouts change under t-dm1 2.4 mg/kg, fixed cycle-1 pk?"],"time_span":{"end":21,"start":0,"step":0.025}},{"controls":[],"description":"Single specified 90-minute infusion followed through day 21; fixed intact-ADC PK coefficients and zero log deviations.","interpretation_guardrails":["Deterministic fixed infusion histories only; no original meta-analysis fitting, sampled population, response prediction or clinical dose selection.","Intact ADC serum is the modeled analyte. The apparent peripheral pool is unmeasured; no receptor, payload or binding mechanism is represented.","T-DM1 and T-DXd use separate reported fixed PK coefficients. Fixed study-level log deviations remain zero in every preset; they are not sampled patient effects.","Reference body weight converts mg/kg to mg only; kinetic coefficients have no weight covariate.","AUC, elapsed day and eliminated amount are nonfeedback observers. Physical day-based AUC units remain unchanged under an hour display.","The terminal half-life readout belongs to the fixed two-compartment coefficient matrix, not a clinical population distribution."],"name":"T-DM1 3.6 mg/kg, fixed cycle-1 PK","outputs":[{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"central_conc_ng_ml","label":"Central conc","unit":"ng/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"auc_ng_day_ml","label":"Exposure (AUC)","unit":"ng*day/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"accounted_adc_mg","label":"Accounted ADC","unit":"mg"},{"classification":"provisional","description":"Fixed-matrix slow-phase half-life; not a clinical population estimate.","key":"fixed_coefficient_terminal_half_life_day","label":"Fixed coefficient terminal half-life","unit":"day"}],"scenario_id":"tdm1_3p6mgkg_cycle1_fixed_effect_ode","scientific_questions":["How do the model's key biological readouts change under t-dm1 3.6 mg/kg, fixed cycle-1 pk?"],"time_span":{"end":21,"start":0,"step":0.025}},{"controls":[],"description":"Single specified 90-minute infusion followed through day 21; fixed intact-ADC PK coefficients and zero log deviations.","interpretation_guardrails":["Deterministic fixed infusion histories only; no original meta-analysis fitting, sampled population, response prediction or clinical dose selection.","Intact ADC serum is the modeled analyte. The apparent peripheral pool is unmeasured; no receptor, payload or binding mechanism is represented.","T-DM1 and T-DXd use separate reported fixed PK coefficients. Fixed study-level log deviations remain zero in every preset; they are not sampled patient effects.","Reference body weight converts mg/kg to mg only; kinetic coefficients have no weight covariate.","AUC, elapsed day and eliminated amount are nonfeedback observers. Physical day-based AUC units remain unchanged under an hour display.","The terminal half-life readout belongs to the fixed two-compartment coefficient matrix, not a clinical population distribution."],"name":"T-DM1 4.8 mg/kg, fixed cycle-1 PK","outputs":[{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"central_conc_ng_ml","label":"Central conc","unit":"ng/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"auc_ng_day_ml","label":"Exposure (AUC)","unit":"ng*day/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"accounted_adc_mg","label":"Accounted ADC","unit":"mg"},{"classification":"provisional","description":"Fixed-matrix slow-phase half-life; not a clinical population estimate.","key":"fixed_coefficient_terminal_half_life_day","label":"Fixed coefficient terminal half-life","unit":"day"}],"scenario_id":"tdm1_4p8mgkg_cycle1_fixed_effect_ode","scientific_questions":["How do the model's key biological readouts change under t-dm1 4.8 mg/kg, fixed cycle-1 pk?"],"time_span":{"end":21,"start":0,"step":0.025}},{"controls":[],"description":"Single specified 90-minute infusion followed through day 21; fixed intact-ADC PK coefficients and zero log deviations.","interpretation_guardrails":["Deterministic fixed infusion histories only; no original meta-analysis fitting, sampled population, response prediction or clinical dose selection.","Intact ADC serum is the modeled analyte. The apparent peripheral pool is unmeasured; no receptor, payload or binding mechanism is represented.","T-DM1 and T-DXd use separate reported fixed PK coefficients. Fixed study-level log deviations remain zero in every preset; they are not sampled patient effects.","Reference body weight converts mg/kg to mg only; kinetic coefficients have no weight covariate.","AUC, elapsed day and eliminated amount are nonfeedback observers. Physical day-based AUC units remain unchanged under an hour display.","The terminal half-life readout belongs to the fixed two-compartment coefficient matrix, not a clinical population distribution."],"name":"T-DXd 0.8 mg/kg, fixed cycle-1 PK","outputs":[{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"central_conc_ng_ml","label":"Central conc","unit":"ng/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"auc_ng_day_ml","label":"Exposure (AUC)","unit":"ng*day/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"accounted_adc_mg","label":"Accounted ADC","unit":"mg"},{"classification":"provisional","description":"Fixed-matrix slow-phase half-life; not a clinical population estimate.","key":"fixed_coefficient_terminal_half_life_day","label":"Fixed coefficient terminal half-life","unit":"day"}],"scenario_id":"tdxd_0p8mgkg_cycle1_fixed_effect_ode","scientific_questions":["How do the model's key biological readouts change under t-dxd 0.8 mg/kg, fixed cycle-1 pk?"],"time_span":{"end":21,"start":0,"step":0.025}},{"controls":[],"description":"Single specified 90-minute infusion followed through day 21; fixed intact-ADC PK coefficients and zero log deviations.","interpretation_guardrails":["Deterministic fixed infusion histories only; no original meta-analysis fitting, sampled population, response prediction or clinical dose selection.","Intact ADC serum is the modeled analyte. The apparent peripheral pool is unmeasured; no receptor, payload or binding mechanism is represented.","T-DM1 and T-DXd use separate reported fixed PK coefficients. Fixed study-level log deviations remain zero in every preset; they are not sampled patient effects.","Reference body weight converts mg/kg to mg only; kinetic coefficients have no weight covariate.","AUC, elapsed day and eliminated amount are nonfeedback observers. Physical day-based AUC units remain unchanged under an hour display.","The terminal half-life readout belongs to the fixed two-compartment coefficient matrix, not a clinical population distribution."],"name":"T-DXd 1.6 mg/kg, fixed cycle-1 PK","outputs":[{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"central_conc_ng_ml","label":"Central conc","unit":"ng/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"auc_ng_day_ml","label":"Exposure (AUC)","unit":"ng*day/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"accounted_adc_mg","label":"Accounted ADC","unit":"mg"},{"classification":"provisional","description":"Fixed-matrix slow-phase half-life; not a clinical population estimate.","key":"fixed_coefficient_terminal_half_life_day","label":"Fixed coefficient terminal half-life","unit":"day"}],"scenario_id":"tdxd_1p6mgkg_cycle1_fixed_effect_ode","scientific_questions":["How do the model's key biological readouts change under t-dxd 1.6 mg/kg, fixed cycle-1 pk?"],"time_span":{"end":21,"start":0,"step":0.025}},{"controls":[],"description":"Single specified 90-minute infusion followed through day 21; fixed intact-ADC PK coefficients and zero log deviations.","interpretation_guardrails":["Deterministic fixed infusion histories only; no original meta-analysis fitting, sampled population, response prediction or clinical dose selection.","Intact ADC serum is the modeled analyte. The apparent peripheral pool is unmeasured; no receptor, payload or binding mechanism is represented.","T-DM1 and T-DXd use separate reported fixed PK coefficients. Fixed study-level log deviations remain zero in every preset; they are not sampled patient effects.","Reference body weight converts mg/kg to mg only; kinetic coefficients have no weight covariate.","AUC, elapsed day and eliminated amount are nonfeedback observers. Physical day-based AUC units remain unchanged under an hour display.","The terminal half-life readout belongs to the fixed two-compartment coefficient matrix, not a clinical population distribution."],"name":"T-DXd 3.2 mg/kg, fixed cycle-1 PK","outputs":[{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"central_conc_ng_ml","label":"Central conc","unit":"ng/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"auc_ng_day_ml","label":"Exposure (AUC)","unit":"ng*day/mL"},{"classification":"provisional","description":"Fixed-context physical amount, concentration, rate or nonfeedback accounting quantity.","key":"accounted_adc_mg","label":"Accounted ADC","unit":"mg"},{"classification":"provisional","description":"Fixed-matrix slow-phase half-life; not a clinical population estimate.","key":"fixed_coefficient_terminal_half_life_day","label":"Fixed coefficient terminal half-life","unit":"day"}],"scenario_id":"tdxd_3p2mgkg_cycle1_fixed_effect_ode","scientific_questions":["How do the model's key biological readouts change under t-dxd 3.2 mg/kg, fixed cycle-1 pk?"],"time_span":{"end":21,"start":0,"step":0.025}},{"controls":[],"description":"Single specified 90-minute infusion followed through day 21; fixed intact-ADC PK coefficients and zero log deviations.","interpretation_guardrails":["Deterministic fixed infusion histories only; no original meta-analysis fitting, sampled population, response prediction or clinical dose selection.","Intact ADC serum is the modeled analyte. The apparent peripheral pool is unmeasured; no receptor, payload or binding mechanism is represented.","T-DM1 and T-DXd use separate reported fixed PK coefficients. Fixed study-level log deviations remain zero in every preset; they are not sampled patient effects.","Reference body weight converts mg/kg to mg only; kinetic coefficients have no weight covariate.","AUC, elapsed day and eliminated amount are nonfeedback observers. 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No antibody PK, dose conversion, full PBPK, population or clinical response is calculated."],"name":"Specified 30 ug/mL exposure","outputs":[{"classification":"provisional","description":"Free CD11a relative to the declared reference abundance, in percent.","key":"free_cd11a_pct","label":"Free cd11a relative to baseline","unit":"%"},{"classification":"provisional","description":"Total free plus bound CD11a relative to the declared reference abundance, in percent.","key":"total_cd11a_pct","label":"Total cd11a relative to baseline","unit":"%"},{"classification":"provisional","description":"Bound fraction of current target, in percent; constant under the specified constant driver.","key":"occupancy_pct","label":"Quasi steady state bound fraction","unit":"%"}],"scenario_id":"high_driver","scientific_questions":["How do the model's key biological readouts change under specified 30 ug/ml exposure?"],"time_span":{"end":672,"start":0,"step":2}},{"controls":[],"description":"CD11a turnover under a specified constant free-antibody concentration. The driver is an external input with no specified physiological matrix.","interpretation_guardrails":["A specified constant free-antibody concentration drives algebraic QSS binding and CD11a turnover; its physiological matrix is unspecified.","Free-target degradation and bound-target internalization use first-order coefficients in inverse hours.","Reference abundance fixes synthesis and normalization. The selected initial target is distinct from this reference, particularly in recovery.","The recovery condition starts from depleted target after exposure removal; it is a separate fixed initial-value calculation.","Cumulative synthesis and loss states and the elapsed-hour clock are nonfeedback observers.","Exposure and parameter ranges are authored research conditions. No antibody PK, dose conversion, full PBPK, population or clinical response is calculated."],"name":"Target recovery after exposure removal","outputs":[{"classification":"provisional","description":"Free CD11a relative to the declared reference abundance, in percent.","key":"free_cd11a_pct","label":"Free cd11a relative to baseline","unit":"%"},{"classification":"provisional","description":"Total free plus bound CD11a relative to the declared reference abundance, in percent.","key":"total_cd11a_pct","label":"Total cd11a relative to baseline","unit":"%"},{"classification":"provisional","description":"Bound fraction of current target, in percent; constant under the specified constant driver.","key":"occupancy_pct","label":"Quasi steady state bound fraction","unit":"%"}],"scenario_id":"washout_recovery","scientific_questions":["How do the model's key biological readouts change under target recovery after exposure removal?"],"time_span":{"end":672,"start":0,"step":2}}],"targets":[{"key":"cd11a","label":"CD11a"},{"key":"itgal","label":"ITGAL"}],"therapeutics":[{"key":"efalizumab","label":"Efalizumab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.2.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"A reduced first-order PASI response model with a fixed treatment-associated asymptote and response half-time.","diseases":[{"key":"plaque_psoriasis","label":"Plaque psoriasis","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.3389/fimmu.2014.00670","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"links":{"page":"/modeling/models/chetty-2014-efalizumab-fcrn-pbpk-pd","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"Whole mAb","model_classes":["Other/Unclassified"],"model_id":"chetty_2014_efalizumab_fcrn_pbpk_pd","name":"Efalizumab reduced PASI progression","outputs":[{"description":"PASI score over the selected simulation window.","key":"PASI_score","label":"PASI score","unit":"dimensionless"},{"description":"Instantaneous signed PASI change; negative values indicate decline.","key":"PASI_change_per_hour","label":"PASI change","unit":"1/hour"},{"description":"Current PASI minus the selected asymptotic PASI.","key":"PASI_gap_to_steady_state","label":"PASI gap to steady state","unit":"dimensionless"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Reduced PASI progression under fixed treated-response parameters; the cohort label identifies context only.","interpretation_guardrails":["Reduced PASI relaxation with a fixed response coefficient and a fixed asymptotic PASI value in each condition.","The elapsed-hour state is a nonfeedback clock. The model has no antibody PK, administered-dose mapping or FcRn compartments.","Two conditions use reported response parameters; two use authored exploratory effective parameters, not reported paper estimates or a reproduced optimizer.","Each initial PASI is fixed by the selected condition. No patient fit, population simulation or clinical efficacy or safety prediction is provided."],"name":"Gottlieb escalating-dose PASI progression probe","outputs":[{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"PASI_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"Instantaneous signed PASI change; negative values indicate decline.","key":"PASI_change_per_hour","label":"PASI change","unit":"1/hour"},{"classification":"provisional","description":"Current PASI minus the selected asymptotic PASI.","key":"PASI_gap_to_steady_state","label":"PASI gap to steady state","unit":"dimensionless"}],"scenario_id":"gottlieb_escalating_pasi_progression_probe","scientific_questions":["How do the model's key biological readouts change under gottlieb escalating-dose pasi progression probe?"],"time_span":{"end":1344,"start":0,"step":24}},{"controls":[],"description":"Reduced PASI progression under fixed treated-response parameters; the cohort label identifies context only.","interpretation_guardrails":["Reduced PASI relaxation with a fixed response coefficient and a fixed asymptotic PASI value in each condition.","The elapsed-hour state is a nonfeedback clock. The model has no antibody PK, administered-dose mapping or FcRn compartments.","Two conditions use reported response parameters; two use authored exploratory effective parameters, not reported paper estimates or a reproduced optimizer.","Each initial PASI is fixed by the selected condition. No patient fit, population simulation or clinical efficacy or safety prediction is provided."],"name":"Gordon 1 mg/kg PASI progression probe","outputs":[{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"PASI_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"Instantaneous signed PASI change; negative values indicate decline.","key":"PASI_change_per_hour","label":"PASI change","unit":"1/hour"},{"classification":"provisional","description":"Current PASI minus the selected asymptotic PASI.","key":"PASI_gap_to_steady_state","label":"PASI gap to steady state","unit":"dimensionless"}],"scenario_id":"gordon_1mgkg_pasi_progression_probe","scientific_questions":["How do the model's key biological readouts change under gordon 1 mg/kg pasi progression probe?"],"time_span":{"end":2016,"start":0,"step":24}},{"controls":[],"description":"Authored exploratory effective response parameters, rather than reported paper estimates or an original fitted model. Fixed initial PASI, response asymptote and response half-time.","interpretation_guardrails":["Reduced PASI relaxation with a fixed response coefficient and a fixed asymptotic PASI value in each condition.","The elapsed-hour state is a nonfeedback clock. The model has no antibody PK, administered-dose mapping or FcRn compartments.","Two conditions use reported response parameters; two use authored exploratory effective parameters, not reported paper estimates or a reproduced optimizer.","Each initial PASI is fixed by the selected condition. No patient fit, population simulation or clinical efficacy or safety prediction is provided."],"name":"Exploratory response condition: Tp=646 h, Yss=8.3","outputs":[{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"PASI_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"Instantaneous signed PASI change; negative values indicate decline.","key":"PASI_change_per_hour","label":"PASI change","unit":"1/hour"},{"classification":"provisional","description":"Current PASI minus the selected asymptotic PASI.","key":"PASI_gap_to_steady_state","label":"PASI gap to steady state","unit":"dimensionless"}],"scenario_id":"exploratory_gottlieb_effective_response","scientific_questions":["How do the model's key biological readouts change under exploratory response condition: tp=646 h, yss=8.3?"],"time_span":{"end":1344,"start":0,"step":24}},{"controls":[],"description":"Authored exploratory effective response parameters, rather than reported paper estimates or an original fitted model. Fixed initial PASI, response asymptote and response half-time.","interpretation_guardrails":["Reduced PASI relaxation with a fixed response coefficient and a fixed asymptotic PASI value in each condition.","The elapsed-hour state is a nonfeedback clock. The model has no antibody PK, administered-dose mapping or FcRn compartments.","Two conditions use reported response parameters; two use authored exploratory effective parameters, not reported paper estimates or a reproduced optimizer.","Each initial PASI is fixed by the selected condition. No patient fit, population simulation or clinical efficacy or safety prediction is provided."],"name":"Exploratory response condition: Tp=1388 h, Yss=2.9","outputs":[{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"PASI_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"Instantaneous signed PASI change; negative values indicate decline.","key":"PASI_change_per_hour","label":"PASI change","unit":"1/hour"},{"classification":"provisional","description":"Current PASI minus the selected asymptotic PASI.","key":"PASI_gap_to_steady_state","label":"PASI gap to steady state","unit":"dimensionless"}],"scenario_id":"exploratory_gordon_effective_response","scientific_questions":["How do the model's key biological readouts change under exploratory response condition: tp=1388 h, yss=2.9?"],"time_span":{"end":2016,"start":0,"step":24}}],"targets":[{"key":"itgal","label":"ITGAL"},{"key":"cd11a","label":"CD11a"},{"key":"lfa_1_alpha","label":"LFA-1 alpha"}],"therapeutics":[{"key":"efalizumab","label":"Efalizumab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.3.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"Explore subcutaneous antibody absorption, apparent two-compartment disposition and quasi-steady-state RANKL binding linked to empirical bone-density turnover. Conditional fixed effects do not establish population behavior or biosimilarity.","diseases":[{"key":"healthy_volunteers_and_postmenopausal_women_with_osteoporosis","label":"Healthy volunteers and postmenopausal women with osteoporosis"}],"links":{"page":"/modeling/models/choi-2025-denosumab-sb16-biosimilarity-poppkpd","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"Whole mAb","model_classes":["QSS target-mediated disposition","empirical bone-density turnover"],"model_id":"choi_2025_denosumab_sb16_biosimilarity_poppkpd","name":"RANKL-directed exposure and bone-density turnover","outputs":[{"description":"Apparent central antibody amount divided by apparent central volume; contains free and algebraically bound antibody.","key":"Ctot_nM","label":"Total central antibody concentration","unit":"nmol/L"},{"description":"Latent quasi-steady-state free-antibody estimate; not a separate observed clinical concentration.","key":"Cfree_nM","label":"Unbound central antibody concentration","unit":"nmol/L"},{"description":"Change relative to model baseline from empirical inhibitory turnover. Healthy-volunteer values are unobserved extrapolations.","key":"bmd_change_percent","label":"Lumbar bone density change","unit":"%"},{"description":"Integral of total central concentration from simulation start; interval AUC requires differences at defined endpoints.","key":"AUC_total_nM_h","label":"Cumulative total antibody exposure","unit":"nmol*h/L"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"What changes when the fitted treatment clearance multiplier is applied to the same dose and covariate context? Fixed-effect exploration; no population or biosimilarity inference.","interpretation_guardrails":["Deterministic fixed-effect trajectories are distinct from population medians, prediction intervals and formal biosimilarity inference.","Dose events contain 408.1632653061224 nmol, representing 60 mg under the retained 147 kDa molecular-weight assumption. Physical amount readouts are in nmol; equivalent events use dimensionless numerical coordinates. No implicit milligram conversion is performed.","Population context is categorical and coupled to the initial target baseline; changing the flag requires coordinated initial-state changes.","Baseline target and BMD parameters are coupled to explicit initial states and are excluded from independent analysis axes.","Disposition volumes and clearances are apparent quantities; target binding is algebraic QSS, not an explicit association/dissociation system.","Healthy-volunteer BMD is an unobserved model extrapolation; its scenario exposes PK only.","BMD change is relative to model baseline and cumulative exposure starts at simulation time zero; neither is automatically a clinical effect estimate or interval AUCtau.","The four non-weight control bounds are exploratory 0.5–1.5× default ranges; no patient distribution or parameter uncertainty is implied.","The Hill state derivative is singular at zero; the existing runtime uses numerical Jacobian boundary regularization. No sensitivity or fitting qualification is asserted.","Population and statistical estimation workflows are outside this conditional fixed-effect candidate."],"name":"Alternate treatment-coefficient context","outputs":[{"classification":"provisional","description":"Apparent central antibody amount divided by apparent central volume; contains free and algebraically bound antibody.","key":"Ctot_nM","label":"Total central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Latent quasi-steady-state free-antibody estimate; not a separate observed clinical concentration.","key":"Cfree_nM","label":"Unbound central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Change relative to model baseline from empirical inhibitory turnover. Healthy-volunteer values are unobserved extrapolations.","key":"bmd_change_percent","label":"Lumbar bone density change","unit":"%"},{"classification":"provisional","description":"Integral of total central concentration from simulation start; interval AUC requires differences at defined endpoints.","key":"AUC_total_nM_h","label":"Cumulative total antibody exposure","unit":"nmol*h/L"}],"scenario_id":"sb16_60mg_q6mo_three_doses_table5_overlay","scientific_questions":["What changes when the fitted treatment clearance multiplier is applied to the same dose and covariate context?"],"time_span":{"end":13140,"start":0,"step":24}},{"controls":[],"description":"How do exposure and empirical bone-density turnover evolve after repeated fixed subcutaneous doses? Fixed-effect exploration; no population or biosimilarity inference.","interpretation_guardrails":["Deterministic fixed-effect trajectories are distinct from population medians, prediction intervals and formal biosimilarity inference.","Dose events contain 408.1632653061224 nmol, representing 60 mg under the retained 147 kDa molecular-weight assumption. Physical amount readouts are in nmol; equivalent events use dimensionless numerical coordinates. No implicit milligram conversion is performed.","Population context is categorical and coupled to the initial target baseline; changing the flag requires coordinated initial-state changes.","Baseline target and BMD parameters are coupled to explicit initial states and are excluded from independent analysis axes.","Disposition volumes and clearances are apparent quantities; target binding is algebraic QSS, not an explicit association/dissociation system.","Healthy-volunteer BMD is an unobserved model extrapolation; its scenario exposes PK only.","BMD change is relative to model baseline and cumulative exposure starts at simulation time zero; neither is automatically a clinical effect estimate or interval AUCtau.","The four non-weight control bounds are exploratory 0.5–1.5× default ranges; no patient distribution or parameter uncertainty is implied.","The Hill state derivative is singular at zero; the existing runtime uses numerical Jacobian boundary regularization. No sensitivity or fitting qualification is asserted.","Population and statistical estimation workflows are outside this conditional fixed-effect candidate."],"name":"Reference osteoporosis context","outputs":[{"classification":"provisional","description":"Apparent central antibody amount divided by apparent central volume; contains free and algebraically bound antibody.","key":"Ctot_nM","label":"Total central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Latent quasi-steady-state free-antibody estimate; not a separate observed clinical concentration.","key":"Cfree_nM","label":"Unbound central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Change relative to model baseline from empirical inhibitory turnover. Healthy-volunteer values are unobserved extrapolations.","key":"bmd_change_percent","label":"Lumbar bone density change","unit":"%"},{"classification":"provisional","description":"Integral of total central concentration from simulation start; interval AUC requires differences at defined endpoints.","key":"AUC_total_nM_h","label":"Cumulative total antibody exposure","unit":"nmol*h/L"}],"scenario_id":"figure6_7_pmo_64kg_caucasian_typical","scientific_questions":["How do exposure and empirical bone-density turnover evolve after repeated fixed subcutaneous doses?"],"time_span":{"end":13140,"start":0,"step":24}},{"controls":[],"description":"Conditional fixed-effect mechanistic probe; no population or clinical prediction.","interpretation_guardrails":["Deterministic fixed-effect trajectories are distinct from population medians, prediction intervals and formal biosimilarity inference.","Dose events contain 408.1632653061224 nmol, representing 60 mg under the retained 147 kDa molecular-weight assumption. Physical amount readouts are in nmol; equivalent events use dimensionless numerical coordinates. No implicit milligram conversion is performed.","Population context is categorical and coupled to the initial target baseline; changing the flag requires coordinated initial-state changes.","Baseline target and BMD parameters are coupled to explicit initial states and are excluded from independent analysis axes.","Disposition volumes and clearances are apparent quantities; target binding is algebraic QSS, not an explicit association/dissociation system.","Healthy-volunteer BMD is an unobserved model extrapolation; its scenario exposes PK only.","BMD change is relative to model baseline and cumulative exposure starts at simulation time zero; neither is automatically a clinical effect estimate or interval AUCtau.","The four non-weight control bounds are exploratory 0.5–1.5× default ranges; no patient distribution or parameter uncertainty is implied.","The Hill state derivative is singular at zero; the existing runtime uses numerical Jacobian boundary regularization. No sensitivity or fitting qualification is asserted.","Population and statistical estimation workflows are outside this conditional fixed-effect candidate."],"name":"Healthy baseline, repeated SC exposure","outputs":[{"classification":"provisional","description":"Apparent central antibody amount divided by apparent central volume; contains free and algebraically bound antibody.","key":"Ctot_nM","label":"Total central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Latent quasi-steady-state free-antibody estimate; not a separate observed clinical concentration.","key":"Cfree_nM","label":"Unbound central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Integral of total central concentration from simulation start; interval AUC requires differences at defined endpoints.","key":"AUC_total_nM_h","label":"Cumulative total antibody exposure","unit":"nmol*h/L"}],"scenario_id":"figure6_7_hv_64kg_caucasian_typical","scientific_questions":["How do exposure and empirical bone-density turnover evolve after repeated fixed subcutaneous doses?"],"time_span":{"end":13140,"start":0,"step":24}},{"controls":[],"description":"How does lower body weight alter conditional exposure and bone-density turnover under the same fixed dose? Fixed-effect exploration; no population or biosimilarity inference.","interpretation_guardrails":["Deterministic fixed-effect trajectories are distinct from population medians, prediction intervals and formal biosimilarity inference.","Dose events contain 408.1632653061224 nmol, representing 60 mg under the retained 147 kDa molecular-weight assumption. Physical amount readouts are in nmol; equivalent events use dimensionless numerical coordinates. No implicit milligram conversion is performed.","Population context is categorical and coupled to the initial target baseline; changing the flag requires coordinated initial-state changes.","Baseline target and BMD parameters are coupled to explicit initial states and are excluded from independent analysis axes.","Disposition volumes and clearances are apparent quantities; target binding is algebraic QSS, not an explicit association/dissociation system.","Healthy-volunteer BMD is an unobserved model extrapolation; its scenario exposes PK only.","BMD change is relative to model baseline and cumulative exposure starts at simulation time zero; neither is automatically a clinical effect estimate or interval AUCtau.","The four non-weight control bounds are exploratory 0.5–1.5× default ranges; no patient distribution or parameter uncertainty is implied.","The Hill state derivative is singular at zero; the existing runtime uses numerical Jacobian boundary regularization. No sensitivity or fitting qualification is asserted.","Population and statistical estimation workflows are outside this conditional fixed-effect candidate."],"name":"Lower-weight osteoporosis context","outputs":[{"classification":"provisional","description":"Apparent central antibody amount divided by apparent central volume; contains free and algebraically bound antibody.","key":"Ctot_nM","label":"Total central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Latent quasi-steady-state free-antibody estimate; not a separate observed clinical concentration.","key":"Cfree_nM","label":"Unbound central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Change relative to model baseline from empirical inhibitory turnover. Healthy-volunteer values are unobserved extrapolations.","key":"bmd_change_percent","label":"Lumbar bone density change","unit":"%"},{"classification":"provisional","description":"Integral of total central concentration from simulation start; interval AUC requires differences at defined endpoints.","key":"AUC_total_nM_h","label":"Cumulative total antibody exposure","unit":"nmol*h/L"}],"scenario_id":"figure6_7_pmo_45kg_caucasian_typical","scientific_questions":["How does lower body weight alter conditional exposure and bone-density turnover under the same fixed dose?"],"time_span":{"end":13140,"start":0,"step":24}},{"controls":[],"description":"How does higher body weight alter conditional exposure and bone-density turnover under the same fixed dose? Fixed-effect exploration; no population or biosimilarity inference.","interpretation_guardrails":["Deterministic fixed-effect trajectories are distinct from population medians, prediction intervals and formal biosimilarity inference.","Dose events contain 408.1632653061224 nmol, representing 60 mg under the retained 147 kDa molecular-weight assumption. Physical amount readouts are in nmol; equivalent events use dimensionless numerical coordinates. No implicit milligram conversion is performed.","Population context is categorical and coupled to the initial target baseline; changing the flag requires coordinated initial-state changes.","Baseline target and BMD parameters are coupled to explicit initial states and are excluded from independent analysis axes.","Disposition volumes and clearances are apparent quantities; target binding is algebraic QSS, not an explicit association/dissociation system.","Healthy-volunteer BMD is an unobserved model extrapolation; its scenario exposes PK only.","BMD change is relative to model baseline and cumulative exposure starts at simulation time zero; neither is automatically a clinical effect estimate or interval AUCtau.","The four non-weight control bounds are exploratory 0.5–1.5× default ranges; no patient distribution or parameter uncertainty is implied.","The Hill state derivative is singular at zero; the existing runtime uses numerical Jacobian boundary regularization. No sensitivity or fitting qualification is asserted.","Population and statistical estimation workflows are outside this conditional fixed-effect candidate."],"name":"Higher-weight osteoporosis context","outputs":[{"classification":"provisional","description":"Apparent central antibody amount divided by apparent central volume; contains free and algebraically bound antibody.","key":"Ctot_nM","label":"Total central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Latent quasi-steady-state free-antibody estimate; not a separate observed clinical concentration.","key":"Cfree_nM","label":"Unbound central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Change relative to model baseline from empirical inhibitory turnover. Healthy-volunteer values are unobserved extrapolations.","key":"bmd_change_percent","label":"Lumbar bone density change","unit":"%"},{"classification":"provisional","description":"Integral of total central concentration from simulation start; interval AUC requires differences at defined endpoints.","key":"AUC_total_nM_h","label":"Cumulative total antibody exposure","unit":"nmol*h/L"}],"scenario_id":"figure6_7_pmo_90kg_caucasian_typical","scientific_questions":["How does higher body weight alter conditional exposure and bone-density turnover under the same fixed dose?"],"time_span":{"end":13140,"start":0,"step":24}},{"controls":[],"description":"Conditional fixed-effect mechanistic probe; no population or clinical prediction.","interpretation_guardrails":["Deterministic fixed-effect trajectories are distinct from population medians, prediction intervals and formal biosimilarity inference.","Dose events contain 408.1632653061224 nmol, representing 60 mg under the retained 147 kDa molecular-weight assumption. Physical amount readouts are in nmol; equivalent events use dimensionless numerical coordinates. No implicit milligram conversion is performed.","Population context is categorical and coupled to the initial target baseline; changing the flag requires coordinated initial-state changes.","Baseline target and BMD parameters are coupled to explicit initial states and are excluded from independent analysis axes.","Disposition volumes and clearances are apparent quantities; target binding is algebraic QSS, not an explicit association/dissociation system.","Healthy-volunteer BMD is an unobserved model extrapolation; its scenario exposes PK only.","BMD change is relative to model baseline and cumulative exposure starts at simulation time zero; neither is automatically a clinical effect estimate or interval AUCtau.","The four non-weight control bounds are exploratory 0.5–1.5× default ranges; no patient distribution or parameter uncertainty is implied.","The Hill state derivative is singular at zero; the existing runtime uses numerical Jacobian boundary regularization. No sensitivity or fitting qualification is asserted.","Population and statistical estimation workflows are outside this conditional fixed-effect candidate."],"name":"Osteoporosis, apparent clearance 0.0069 L/h","outputs":[{"classification":"provisional","description":"Apparent central antibody amount divided by apparent central volume; contains free and algebraically bound antibody.","key":"Ctot_nM","label":"Total central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Latent quasi-steady-state free-antibody estimate; not a separate observed clinical concentration.","key":"Cfree_nM","label":"Unbound central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Change relative to model baseline from empirical inhibitory turnover. Healthy-volunteer values are unobserved extrapolations.","key":"bmd_change_percent","label":"Lumbar bone density change","unit":"%"},{"classification":"provisional","description":"Integral of total central concentration from simulation start; interval AUC requires differences at defined endpoints.","key":"AUC_total_nM_h","label":"Cumulative total antibody exposure","unit":"nmol*h/L"}],"scenario_id":"figure6_7_pmo_64kg_black_typical","scientific_questions":["How do exposure and empirical bone-density turnover evolve after repeated fixed subcutaneous doses?"],"time_span":{"end":13140,"start":0,"step":24}},{"controls":[],"description":"Conditional fixed-effect mechanistic probe; no population or clinical prediction.","interpretation_guardrails":["Deterministic fixed-effect trajectories are distinct from population medians, prediction intervals and formal biosimilarity inference.","Dose events contain 408.1632653061224 nmol, representing 60 mg under the retained 147 kDa molecular-weight assumption. Physical amount readouts are in nmol; equivalent events use dimensionless numerical coordinates. No implicit milligram conversion is performed.","Population context is categorical and coupled to the initial target baseline; changing the flag requires coordinated initial-state changes.","Baseline target and BMD parameters are coupled to explicit initial states and are excluded from independent analysis axes.","Disposition volumes and clearances are apparent quantities; target binding is algebraic QSS, not an explicit association/dissociation system.","Healthy-volunteer BMD is an unobserved model extrapolation; its scenario exposes PK only.","BMD change is relative to model baseline and cumulative exposure starts at simulation time zero; neither is automatically a clinical effect estimate or interval AUCtau.","The four non-weight control bounds are exploratory 0.5–1.5× default ranges; no patient distribution or parameter uncertainty is implied.","The Hill state derivative is singular at zero; the existing runtime uses numerical Jacobian boundary regularization. No sensitivity or fitting qualification is asserted.","Population and statistical estimation workflows are outside this conditional fixed-effect candidate."],"name":"Osteoporosis, apparent clearance 0.0074 L/h","outputs":[{"classification":"provisional","description":"Apparent central antibody amount divided by apparent central volume; contains free and algebraically bound antibody.","key":"Ctot_nM","label":"Total central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Latent quasi-steady-state free-antibody estimate; not a separate observed clinical concentration.","key":"Cfree_nM","label":"Unbound central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Change relative to model baseline from empirical inhibitory turnover. Healthy-volunteer values are unobserved extrapolations.","key":"bmd_change_percent","label":"Lumbar bone density change","unit":"%"},{"classification":"provisional","description":"Integral of total central concentration from simulation start; interval AUC requires differences at defined endpoints.","key":"AUC_total_nM_h","label":"Cumulative total antibody exposure","unit":"nmol*h/L"}],"scenario_id":"figure6_7_pmo_64kg_asian_typical","scientific_questions":["How do exposure and empirical bone-density turnover evolve after repeated fixed subcutaneous doses?"],"time_span":{"end":13140,"start":0,"step":24}},{"controls":[],"description":"Conditional fixed-effect mechanistic probe; no population or clinical prediction.","interpretation_guardrails":["Deterministic fixed-effect trajectories are distinct from population medians, prediction intervals and formal biosimilarity inference.","Dose events contain 408.1632653061224 nmol, representing 60 mg under the retained 147 kDa molecular-weight assumption. Physical amount readouts are in nmol; equivalent events use dimensionless numerical coordinates. No implicit milligram conversion is performed.","Population context is categorical and coupled to the initial target baseline; changing the flag requires coordinated initial-state changes.","Baseline target and BMD parameters are coupled to explicit initial states and are excluded from independent analysis axes.","Disposition volumes and clearances are apparent quantities; target binding is algebraic QSS, not an explicit association/dissociation system.","Healthy-volunteer BMD is an unobserved model extrapolation; its scenario exposes PK only.","BMD change is relative to model baseline and cumulative exposure starts at simulation time zero; neither is automatically a clinical effect estimate or interval AUCtau.","The four non-weight control bounds are exploratory 0.5–1.5× default ranges; no patient distribution or parameter uncertainty is implied.","The Hill state derivative is singular at zero; the existing runtime uses numerical Jacobian boundary regularization. No sensitivity or fitting qualification is asserted.","Population and statistical estimation workflows are outside this conditional fixed-effect candidate."],"name":"Untreated osteoporosis baseline","outputs":[{"classification":"provisional","description":"Apparent central antibody amount divided by apparent central volume; contains free and algebraically bound antibody.","key":"Ctot_nM","label":"Total central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Latent quasi-steady-state free-antibody estimate; not a separate observed clinical concentration.","key":"Cfree_nM","label":"Unbound central antibody concentration","unit":"nmol/L"},{"classification":"provisional","description":"Change relative to model baseline from empirical inhibitory turnover. 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compare with delivered ADC mass.","key":"adc_accounted_mg","label":"ADC accounted","unit":"mg"},{"classification":"provisional","description":"Current MMAE amount plus accumulated MMAE elimination; compare with stoichiometric cumulative MMAE formation.","key":"mmae_accounted_mg","label":"MMAE accounted","unit":"mg"}],"scenario_id":"brentuximab_ddi_window_fixed_higher_mmae_clearance","scientific_questions":["How do the model's key biological readouts change under brentuximab declared amount reference; fixed_higher_mmae_clearance?"],"time_span":{"end":2000,"start":0,"step":1}}],"targets":[{"key":"pvrl4","label":"PVRL4","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s10928-023-09877-5","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}},{"key":"nectin_4","label":"Nectin-4","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s10928-023-09877-5","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"therapeutics":[{"key":"enfortumab_vedotin_brentuximab_vedotin_and_mmae","label":"Enfortumab vedotin, brentuximab vedotin and MMAE"},{"key":"enfortumab_vedotin","label":"Enfortumab vedotin"},{"key":"brentuximab_vedotin","label":"Brentuximab vedotin"},{"key":"monomethyl_auristatin_e","label":"Monomethyl auristatin E"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.1.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"Two-compartment total-serum PK with explicit IM/IV administration, fixed covariates and empirical input-weighted amount accounting.","diseases":[{"key":"sars_cov_2_pre_exposure_prophylaxis","label":"SARS-CoV-2 pre-exposure prophylaxis","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1128/aac.01587-23","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"links":{"page":"/modeling/models/clegg-2024-azd7442-tixagevimab-cilgavimab-poppk","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"Whole mAb","model_classes":["Two-compartment PK","Fixed covariates"],"model_id":"clegg_2024_azd7442_tixagevimab_cilgavimab_poppk","name":"AZD7442 total-antibody pharmacokinetics","outputs":[{"description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. The model does not calculate separate component trajectories or antibody binding or clinical response.","Covariates remain fixed within each condition. Their empirical associations do not establish causal mechanisms.","The IM/site factor scales model exposure input and may exceed one. Its apparent input-weighted ledger differs from nominal administered mass.","Three amount states describe depot, central and peripheral PK. AUC and elapsed time are nonfeedback observers.","The current amount and CL-times-AUC readouts use fixed context coefficients. The input-weighted ledger weights the depot by the same empirical IM factor.","Each administration explicitly targets depot or central amount. The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"fig4 typical 600mg gluteal azd7442","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"fig4_typical_600mg_gluteal_azd7442","scientific_questions":["How do the model's key biological readouts change under fig4 typical 600mg gluteal azd7442?"],"time_span":{"end":1000,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. The model does not calculate separate component trajectories or antibody binding or clinical response.","Covariates remain fixed within each condition. Their empirical associations do not establish causal mechanisms.","The IM/site factor scales model exposure input and may exceed one. Its apparent input-weighted ledger differs from nominal administered mass.","Three amount states describe depot, central and peripheral PK. AUC and elapsed time are nonfeedback observers.","The current amount and CL-times-AUC readouts use fixed context coefficients. The input-weighted ledger weights the depot by the same empirical IM factor.","Each administration explicitly targets depot or central amount. The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"fig4 high weight 600mg gluteal azd7442","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"fig4_high_weight_600mg_gluteal_azd7442","scientific_questions":["How do the model's key biological readouts change under fig4 high weight 600mg gluteal azd7442?"],"time_span":{"end":1000,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. The model does not calculate separate component trajectories or antibody binding or clinical response.","Covariates remain fixed within each condition. Their empirical associations do not establish causal mechanisms.","The IM/site factor scales model exposure input and may exceed one. Its apparent input-weighted ledger differs from nominal administered mass.","Three amount states describe depot, central and peripheral PK. AUC and elapsed time are nonfeedback observers.","The current amount and CL-times-AUC readouts use fixed context coefficients. The input-weighted ledger weights the depot by the same empirical IM factor.","Each administration explicitly targets depot or central amount. The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"fig5 prep 300mg single azd7442","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"fig5_prep_300mg_single_azd7442","scientific_questions":["How do the model's key biological readouts change under fig5 prep 300mg single azd7442?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. The model does not calculate separate component trajectories or antibody binding or clinical response.","Covariates remain fixed within each condition. Their empirical associations do not establish causal mechanisms.","The IM/site factor scales model exposure input and may exceed one. Its apparent input-weighted ledger differs from nominal administered mass.","Three amount states describe depot, central and peripheral PK. AUC and elapsed time are nonfeedback observers.","The current amount and CL-times-AUC readouts use fixed context coefficients. The input-weighted ledger weights the depot by the same empirical IM factor.","Each administration explicitly targets depot or central amount. The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"fig5 adolescent 40kg 300mg azd7442","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"fig5_adolescent_40kg_300mg_azd7442","scientific_questions":["How do the model's key biological readouts change under fig5 adolescent 40kg 300mg azd7442?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. The model does not calculate separate component trajectories or antibody binding or clinical response.","Covariates remain fixed within each condition. Their empirical associations do not establish causal mechanisms.","The IM/site factor scales model exposure input and may exceed one. Its apparent input-weighted ledger differs from nominal administered mass.","Three amount states describe depot, central and peripheral PK. AUC and elapsed time are nonfeedback observers.","The current amount and CL-times-AUC readouts use fixed context coefficients. The input-weighted ledger weights the depot by the same empirical IM factor.","Each administration explicitly targets depot or central amount. The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"fig4 aged over65 600mg combination total","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"fig4_aged_over65_600mg_combination_total","scientific_questions":["How do the model's key biological readouts change under fig4 aged over65 600mg combination total?"],"time_span":{"end":1000,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. The model does not calculate separate component trajectories or antibody binding or clinical response.","Covariates remain fixed within each condition. Their empirical associations do not establish causal mechanisms.","The IM/site factor scales model exposure input and may exceed one. Its apparent input-weighted ledger differs from nominal administered mass.","Three amount states describe depot, central and peripheral PK. AUC and elapsed time are nonfeedback observers.","The current amount and CL-times-AUC readouts use fixed context coefficients. The input-weighted ledger weights the depot by the same empirical IM factor.","Each administration explicitly targets depot or central amount. The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"fig4 female 600mg combination total","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"fig4_female_600mg_combination_total","scientific_questions":["How do the model's key biological readouts change under fig4 female 600mg combination total?"],"time_span":{"end":1000,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. The model does not calculate separate component trajectories or antibody binding or clinical response.","Covariates remain fixed within each condition. Their empirical associations do not establish causal mechanisms.","The IM/site factor scales model exposure input and may exceed one. Its apparent input-weighted ledger differs from nominal administered mass.","Three amount states describe depot, central and peripheral PK. AUC and elapsed time are nonfeedback observers.","The current amount and CL-times-AUC readouts use fixed context coefficients. The input-weighted ledger weights the depot by the same empirical IM factor.","Each administration explicitly targets depot or central amount. The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"fig4 low weight 600mg combination total","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"fig4_low_weight_600mg_combination_total","scientific_questions":["How do the model's key biological readouts change under fig4 low weight 600mg combination total?"],"time_span":{"end":1000,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. The model does not calculate separate component trajectories or antibody binding or clinical response.","Covariates remain fixed within each condition. Their empirical associations do not establish causal mechanisms.","The IM/site factor scales model exposure input and may exceed one. Its apparent input-weighted ledger differs from nominal administered mass.","Three amount states describe depot, central and peripheral PK. AUC and elapsed time are nonfeedback observers.","The current amount and CL-times-AUC readouts use fixed context coefficients. The input-weighted ledger weights the depot by the same empirical IM factor.","Each administration explicitly targets depot or central amount. The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"fig4 bmi ge30 600mg combination total","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"fig4_bmi_ge30_600mg_combination_total","scientific_questions":["How do the model's key biological readouts change under fig4 bmi ge30 600mg combination total?"],"time_span":{"end":1000,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. The model does not calculate separate component trajectories or antibody binding or clinical response.","Covariates remain fixed within each condition. Their empirical associations do not establish causal mechanisms.","The IM/site factor scales model exposure input and may exceed one. Its apparent input-weighted ledger differs from nominal administered mass.","Three amount states describe depot, central and peripheral PK. AUC and elapsed time are nonfeedback observers.","The current amount and CL-times-AUC readouts use fixed context coefficients. The input-weighted ledger weights the depot by the same empirical IM factor.","Each administration explicitly targets depot or central amount. The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"fig4 diabetes 600mg combination total","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"fig4_diabetes_600mg_combination_total","scientific_questions":["How do the model's key biological readouts change under fig4 diabetes 600mg combination total?"],"time_span":{"end":1000,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. The model does not calculate separate component trajectories or antibody binding or clinical response.","Covariates remain fixed within each condition. Their empirical associations do not establish causal mechanisms.","The IM/site factor scales model exposure input and may exceed one. Its apparent input-weighted ledger differs from nominal administered mass.","Three amount states describe depot, central and peripheral PK. AUC and elapsed time are nonfeedback observers.","The current amount and CL-times-AUC readouts use fixed context coefficients. The input-weighted ledger weights the depot by the same empirical IM factor.","Each administration explicitly targets depot or central amount. The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"fig4 black 600mg combination total","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"fig4_black_600mg_combination_total","scientific_questions":["How do the model's key biological readouts change under fig4 black 600mg combination total?"],"time_span":{"end":1000,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. The model does not calculate separate component trajectories or antibody binding or clinical response.","Covariates remain fixed within each condition. Their empirical associations do not establish causal mechanisms.","The IM/site factor scales model exposure input and may exceed one. Its apparent input-weighted ledger differs from nominal administered mass.","Three amount states describe depot, central and peripheral PK. AUC and elapsed time are nonfeedback observers.","The current amount and CL-times-AUC readouts use fixed context coefficients. The input-weighted ledger weights the depot by the same empirical IM factor.","Each administration explicitly targets depot or central amount. 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The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"fig4 combined low 600mg combination total","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"fig4_combined_low_600mg_combination_total","scientific_questions":["How do the model's key biological readouts change under fig4 combined low 600mg combination total?"],"time_span":{"end":1000,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. 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The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"table reference 70kg female total","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"table_reference_70kg_female_total","scientific_questions":["How do the model's key biological readouts change under table reference 70kg female total?"],"time_span":{"end":1000,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. 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The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"iv 300mg combination 1h assumption total","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"iv_300mg_combination_1h_assumption_total","scientific_questions":["How do the model's key biological readouts change under iv 300mg combination 1h assumption total?"],"time_span":{"end":360,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. 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The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"iv 600mg combination 1h assumption total","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"iv_600mg_combination_1h_assumption_total","scientific_questions":["How do the model's key biological readouts change under iv 600mg combination 1h assumption total?"],"time_span":{"end":360,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. 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The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"iv 1000mg combination 1h assumption total","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"iv_1000mg_combination_1h_assumption_total","scientific_questions":["How do the model's key biological readouts change under iv 1000mg combination 1h assumption total?"],"time_span":{"end":360,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate total-serum PK following the specified explicit administrations.","interpretation_guardrails":["The analyte is total AZD7442 serum concentration. 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The selected condition fixes the initial values, coefficients and administration history.","No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided."],"name":"iv 3000mg combination 1h assumption total","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Cavg cum over the selected simulation window.","key":"Cavg_cum_ug_ml","label":"Cavg cum","unit":"ug/mL"}],"scenario_id":"iv_3000mg_combination_1h_assumption_total","scientific_questions":["How do the model's key biological readouts change under iv 3000mg combination 1h assumption total?"],"time_span":{"end":360,"start":0,"step":1}}],"targets":[{"key":"sars_cov_2_spike_rbd","label":"SARS-CoV-2 Spike RBD","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1128/aac.01587-23","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"therapeutics":[{"key":"azd7442_total_antibody_analyte","label":"AZD7442 (total-antibody analyte)"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.3.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"Explore serum cilgavimab exposure with fixed patient covariates using the publication’s main coefficient profile. 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All administration targets are explicit.","Covariates stay fixed within each history; categorical associations do not imply causal mechanisms.","The peripheral pool is apparent. 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All administration targets are explicit.","Covariates stay fixed within each history; categorical associations do not imply causal mechanisms.","The peripheral pool is apparent. AUC and elapsed time are nonfeedback observers.","The component ledger weights the nominal IM depot by FIM; separately fitted component and total-model curves are not constrained to sum.","No arbitrary control ranges, sampling, likelihood, fitting, viral dynamics, efficacy or individual treatment advice is provided."],"name":"Cilgavimab 300 mg IM fixed covariate reference","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Empirical input accounted over the selected simulation window.","key":"empirical_input_accounted_mg","label":"Empirical input accounted","unit":"mg"}],"scenario_id":"fig4_high_weight_600mg_combination","scientific_questions":["How do the model's key biological readouts change under cilgavimab 300 mg im fixed covariate reference?"],"time_span":{"end":1000,"start":0,"step":1}},{"controls":[],"description":"Cilgavimab fixed-covariate main Table 1 reference with explicit per-component administration.","interpretation_guardrails":["Fixed component serum PK with main Table 1 coefficient values; no original cohort fit or population reproduction.","Each history gives a per-component 300 mg dose, the corresponding part of a 600 mg 1:1 AZD7442 combination.","One-hour IV duration is an explicit research assumption. 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All administration targets are explicit.","Covariates stay fixed within each history; categorical associations do not imply causal mechanisms.","The peripheral pool is apparent. AUC and elapsed time are nonfeedback observers.","The component ledger weights the nominal IM depot by FIM; separately fitted component and total-model curves are not constrained to sum.","No arbitrary control ranges, sampling, likelihood, fitting, viral dynamics, efficacy or individual treatment advice is provided."],"name":"Cilgavimab 300 mg IV over 1 hour fixed covariate reference","outputs":[{"classification":"provisional","description":"Central conc over the selected simulation window.","key":"central_conc_ug_ml","label":"Central conc","unit":"ug/mL"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_ml","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Empirical input accounted over the selected simulation window.","key":"empirical_input_accounted_mg","label":"Empirical input accounted","unit":"mg"}],"scenario_id":"iv_600mg_combination_1h_assumption","scientific_questions":["How do the model's key biological readouts change under cilgavimab 300 mg iv over 1 hour fixed covariate reference?"],"time_span":{"end":360,"start":0,"step":1}}],"targets":[{"key":"sars_cov_2_spike_rbd","label":"SARS-CoV-2 Spike RBD","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1128/aac.01587-23","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"therapeutics":[{"key":"cilgavimab","label":"Cilgavimab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.2.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"Explore serum tixagevimab exposure with fixed patient covariates using the publication’s main coefficient profile. 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All administration targets are explicit.","Covariates stay fixed within each history; categorical associations do not imply causal mechanisms.","The peripheral pool is apparent. 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An infusion beginning at the observation endpoint delivers no amount before that endpoint.","Cumulative eliminated amount integrates instantaneous total clearance times central concentration; exposure and accounting do not feed back.","The clearance-arm decay half-time is not a terminal drug half-life.","No explicit CD22 binding, tumor response, payload kinetics, clinical dose advice, original patient fit or population predictive check is represented."],"name":"ALL fixed high covariate projection, extended observation grid","outputs":[{"classification":"provisional","description":"Serum model readout:1000 times central mg divided by apparent central L.","key":"central_concentration_ng_mL","label":"Central concentration","unit":"ng/mL"},{"classification":"provisional","description":"Nonfeedback integral of central serum concentration; physical hour-based AUC persists under alternative display clocks.","key":"AUC_ng_h_mL","label":"Exposure (AUC)","unit":"ng*h/mL"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_total_L_h","label":"Clearance total","unit":"L/h"},{"classification":"provisional","description":"Current central and peripheral amounts plus integrated cumulative elimination.","key":"accounted_inotuzumab_mg","label":"Accounted inotuzumab","unit":"mg"}],"scenario_id":"fixed_vignette_all_high","scientific_questions":["How do the model's key biological readouts change under all fixed high covariate projection, extended observation grid?"],"time_span":{"end":1848,"start":0,"step":12}}],"targets":[{"key":"siglec2","label":"SIGLEC2","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s10928-018-9614-9","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}},{"key":"cd22","label":"CD22","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s10928-018-9614-9","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}},{"key":"b_cell_receptor_cd22","label":"B-cell receptor CD22","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s10928-018-9614-9","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"therapeutics":[{"key":"inotuzumab_ozogamicin","label":"Inotuzumab ozogamicin"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.3.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"A QSS-TMDD model representing intravenous or subcutaneous befovacimab disposition, TFPI turnover, free antibody, and antibody–TFPI complex dynamics.","diseases":[{"key":"translational_hemophilia_prophylaxis","label":"Translational hemophilia prophylaxis"}],"links":{"page":"/modeling/models/gu-2017-bay1093884-tfpi-qss-tmdd","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"Whole mAb","model_classes":["PKPD","TMDD"],"model_id":"gu_2017_bay1093884_tfpi_qss_tmdd","name":"Befovacimab PK and TFPI target binding","outputs":[{"description":"Total central befovacimab over the selected simulation window.","key":"central_total_mg_L","label":"Total central befovacimab","unit":null},{"description":"Free central befovacimab over the selected simulation window.","key":"central_free_nM","label":"Free central befovacimab","unit":null},{"description":"Total target concentration over the selected simulation window.","key":"target_total_nM","label":"Total target concentration","unit":"nM"},{"description":"Befovacimab TFPI complex over the selected simulation window.","key":"complex_nM","label":"Befovacimab TFPI complex","unit":null},{"description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_h_L","label":"Exposure (AUC)","unit":"mg*h/L"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[{"category":"model parameter","definition":"Systemic clearance governing removal of modeled material from the relevant compartment.","description":"Systemic clearance governing removal of modeled material from the relevant compartment.","key":"cl_L_h_kg","label":"Systemic clearance","max":0.0004305,"min":0.0001435,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; 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Explore this biological starting configuration through Total central befovacimab, Free central befovacimab, Total TFPI, Befovacimab–TFPI complex, Cumulative exposure.","interpretation_guardrails":["Interpret trajectories as deterministic model behavior, not as a patient-specific prediction or dosing recommendation.","Paper-result and exact-anchor checks remain in the private validation lane and are not part of this public scenario."],"name":"cynomolgus IV 5 mg/kg QSS-TMDD","outputs":[{"classification":"provisional","description":"Total central befovacimab over the selected simulation window.","key":"central_total_mg_L","label":"Total central befovacimab","unit":null},{"classification":"provisional","description":"Free central befovacimab over the selected simulation window.","key":"central_free_nM","label":"Free central befovacimab","unit":null},{"classification":"provisional","description":"Total target concentration over the selected simulation window.","key":"target_total_nM","label":"Total target concentration","unit":"nM"},{"classification":"provisional","description":"Befovacimab TFPI complex over the selected simulation window.","key":"complex_nM","label":"Befovacimab TFPI complex","unit":null},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_h_L","label":"Exposure (AUC)","unit":"mg*h/L"}],"scenario_id":"gu_2017_cyno_iv5mgkg_qss_tmdd_probe","scientific_questions":["How do route and dose change befovacimab exposure, free antibody, TFPI, and bound complex?"],"time_span":{"end":720,"start":0,"step":1}},{"controls":[{"category":"model parameter","definition":"Systemic clearance governing removal of modeled material from the relevant compartment.","description":"Systemic clearance governing removal of modeled material from the relevant compartment.","key":"cl_L_h_kg","label":"Systemic clearance","max":0.0004305,"min":0.0001435,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1e-06,"unit":"L/h/kg","value":0.000287},{"category":"model parameter","definition":"Central distribution volume used to convert modeled amount to concentration in the relevant compartment.","description":"Central distribution volume used to convert modeled amount to concentration in the relevant compartment.","key":"vc_L_kg","label":"Central distribution volume","max":0.07365,"min":0.02455,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":9.999999999999999e-05,"unit":"L/kg","value":0.0491},{"category":"model parameter","definition":"Quasi-steady-state binding constant describing equilibrium binding affinity in the modeled interaction.","description":"Quasi-steady-state binding constant describing equilibrium binding affinity in the modeled interaction.","key":"kss_nM","label":"Quasi-steady-state binding constant","max":348,"min":116,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"nM","value":232},{"category":"model parameter","definition":"Target internalization rate coefficient used by the released system of model equations.","description":"Target internalization rate coefficient used by the released system of model equations.","key":"kint_h","label":"Target internalization rate","max":83.1,"min":27.7,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.1,"unit":"1/h","value":55.4},{"category":"model parameter","definition":"Target synthesis rate governing production or formation in the modeled biological process.","description":"Target synthesis rate governing production or formation in the modeled biological process.","key":"ksyn_nM_h","label":"Target synthesis rate","max":3.9000000000000004,"min":1.3,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.01,"unit":"nM/h","value":2.6}],"description":"How do route and dose change befovacimab exposure, free antibody, TFPI, and bound complex? Explore this biological starting configuration through Total central befovacimab, Free central befovacimab, Total TFPI, Befovacimab–TFPI complex, Cumulative exposure.","interpretation_guardrails":["Interpret trajectories as deterministic model behavior, not as a patient-specific prediction or dosing recommendation.","Paper-result and exact-anchor checks remain in the private validation lane and are not part of this public scenario."],"name":"cynomolgus IV 20 mg/kg QSS-TMDD","outputs":[{"classification":"provisional","description":"Total central befovacimab over the selected simulation window.","key":"central_total_mg_L","label":"Total central befovacimab","unit":null},{"classification":"provisional","description":"Free central befovacimab over the selected simulation window.","key":"central_free_nM","label":"Free central befovacimab","unit":null},{"classification":"provisional","description":"Total target concentration over the selected simulation window.","key":"target_total_nM","label":"Total target concentration","unit":"nM"},{"classification":"provisional","description":"Befovacimab TFPI complex over the selected simulation window.","key":"complex_nM","label":"Befovacimab TFPI complex","unit":null},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_h_L","label":"Exposure (AUC)","unit":"mg*h/L"}],"scenario_id":"gu_2017_cyno_iv20mgkg_qss_tmdd_probe","scientific_questions":["How do route and dose change befovacimab exposure, free antibody, TFPI, and bound complex?"],"time_span":{"end":1008,"start":0,"step":1}},{"controls":[{"category":"model parameter","definition":"Systemic clearance governing removal of modeled material from the relevant compartment.","description":"Systemic clearance governing removal of modeled material from the relevant compartment.","key":"cl_L_h_kg","label":"Systemic clearance","max":0.0004305,"min":0.0001435,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1e-06,"unit":"L/h/kg","value":0.000287},{"category":"model parameter","definition":"Central distribution volume used to convert modeled amount to concentration in the relevant compartment.","description":"Central distribution volume used to convert modeled amount to concentration in the relevant compartment.","key":"vc_L_kg","label":"Central distribution volume","max":0.07365,"min":0.02455,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":9.999999999999999e-05,"unit":"L/kg","value":0.0491},{"category":"model parameter","definition":"Quasi-steady-state binding constant describing equilibrium binding affinity in the modeled interaction.","description":"Quasi-steady-state binding constant describing equilibrium binding affinity in the modeled interaction.","key":"kss_nM","label":"Quasi-steady-state binding constant","max":348,"min":116,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"nM","value":232},{"category":"model parameter","definition":"Target internalization rate coefficient used by the released system of model equations.","description":"Target internalization rate coefficient used by the released system of model equations.","key":"kint_h","label":"Target internalization rate","max":83.1,"min":27.7,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.1,"unit":"1/h","value":55.4},{"category":"model parameter","definition":"Target synthesis rate governing production or formation in the modeled biological process.","description":"Target synthesis rate governing production or formation in the modeled biological process.","key":"ksyn_nM_h","label":"Target synthesis rate","max":3.9000000000000004,"min":1.3,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.01,"unit":"nM/h","value":2.6}],"description":"How do route and dose change befovacimab exposure, free antibody, TFPI, and bound complex? Explore this biological starting configuration through Total central befovacimab, Free central befovacimab, Total TFPI, Befovacimab–TFPI complex, Cumulative exposure.","interpretation_guardrails":["Interpret trajectories as deterministic model behavior, not as a patient-specific prediction or dosing recommendation.","Paper-result and exact-anchor checks remain in the private validation lane and are not part of this public scenario."],"name":"Human 0.4 mg/kg","outputs":[{"classification":"provisional","description":"Total central befovacimab over the selected simulation window.","key":"central_total_mg_L","label":"Total central befovacimab","unit":null},{"classification":"provisional","description":"Free central befovacimab over the selected simulation window.","key":"central_free_nM","label":"Free central befovacimab","unit":null},{"classification":"provisional","description":"Total target concentration over the selected simulation window.","key":"target_total_nM","label":"Total target concentration","unit":"nM"},{"classification":"provisional","description":"Befovacimab TFPI complex over the selected simulation window.","key":"complex_nM","label":"Befovacimab TFPI complex","unit":null},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_h_L","label":"Exposure (AUC)","unit":"mg*h/L"}],"scenario_id":"gu_2017_human_0p4mgkg_iv_source_limited","scientific_questions":["How do route and dose change befovacimab exposure, free antibody, TFPI, and bound complex?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[{"category":"model parameter","definition":"Systemic clearance governing removal of modeled material from the relevant compartment.","description":"Systemic clearance governing removal of modeled material from the relevant compartment.","key":"cl_L_h_kg","label":"Systemic clearance","max":0.0004305,"min":0.0001435,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1e-06,"unit":"L/h/kg","value":0.000287},{"category":"model parameter","definition":"Central distribution volume used to convert modeled amount to concentration in the relevant compartment.","description":"Central distribution volume used to convert modeled amount to concentration in the relevant compartment.","key":"vc_L_kg","label":"Central distribution volume","max":0.07365,"min":0.02455,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":9.999999999999999e-05,"unit":"L/kg","value":0.0491},{"category":"model parameter","definition":"Quasi-steady-state binding constant describing equilibrium binding affinity in the modeled interaction.","description":"Quasi-steady-state binding constant describing equilibrium binding affinity in the modeled interaction.","key":"kss_nM","label":"Quasi-steady-state binding constant","max":348,"min":116,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"nM","value":232},{"category":"model parameter","definition":"Target internalization rate coefficient used by the released system of model equations.","description":"Target internalization rate coefficient used by the released system of model equations.","key":"kint_h","label":"Target internalization rate","max":83.1,"min":27.7,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.1,"unit":"1/h","value":55.4},{"category":"model parameter","definition":"Target synthesis rate governing production or formation in the modeled biological process.","description":"Target synthesis rate governing production or formation in the modeled biological process.","key":"ksyn_nM_h","label":"Target synthesis rate","max":3.9000000000000004,"min":1.3,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.01,"unit":"nM/h","value":2.6}],"description":"How do route and dose change befovacimab exposure, free antibody, TFPI, and bound complex? Explore this biological starting configuration through Total central befovacimab, Free central befovacimab, Total TFPI, Befovacimab–TFPI complex, Cumulative exposure.","interpretation_guardrails":["Interpret trajectories as deterministic model behavior, not as a patient-specific prediction or dosing recommendation.","Paper-result and exact-anchor checks remain in the private validation lane and are not part of this public scenario."],"name":"cynomolgus SC 5 mg/kg","outputs":[{"classification":"provisional","description":"Total central befovacimab over the selected simulation window.","key":"central_total_mg_L","label":"Total central befovacimab","unit":null},{"classification":"provisional","description":"Free central befovacimab over the selected simulation window.","key":"central_free_nM","label":"Free central befovacimab","unit":null},{"classification":"provisional","description":"Total target concentration over the selected simulation window.","key":"target_total_nM","label":"Total target concentration","unit":"nM"},{"classification":"provisional","description":"Befovacimab TFPI complex over the selected simulation window.","key":"complex_nM","label":"Befovacimab TFPI complex","unit":null},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_h_L","label":"Exposure (AUC)","unit":"mg*h/L"}],"scenario_id":"gu_2017_exploratory_calibrated_cyno_sc5mgkg_joint_figures2_4_5_6_table2","scientific_questions":["How do route and dose change befovacimab exposure, free antibody, TFPI, and bound complex?"],"time_span":{"end":528,"start":0,"step":0.5}},{"controls":[{"category":"model parameter","definition":"Systemic clearance governing removal of modeled material from the relevant compartment.","description":"Systemic clearance governing removal of modeled material from the relevant compartment.","key":"cl_L_h_kg","label":"Systemic clearance","max":0.003832851905342577,"min":0.001277617301780859,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":9.999999999999999e-06,"unit":"L/h/kg","value":0.002555234603561718},{"category":"model parameter","definition":"Central distribution volume used to convert modeled amount to concentration in the relevant compartment.","description":"Central distribution volume used to convert modeled amount to concentration in the relevant compartment.","key":"vc_L_kg","label":"Central distribution volume","max":0.07692307692307693,"min":0.025641025641025644,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":9.999999999999999e-05,"unit":"L/kg","value":0.05128205128205129},{"category":"model parameter","definition":"Quasi-steady-state binding constant describing equilibrium binding affinity in the modeled interaction.","description":"Quasi-steady-state binding constant describing equilibrium binding affinity in the modeled interaction.","key":"kss_nM","label":"Quasi-steady-state binding constant","max":348,"min":116,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"nM","value":232},{"category":"model parameter","definition":"Target internalization rate coefficient used by the released system of model equations.","description":"Target internalization rate coefficient used by the released system of model equations.","key":"kint_h","label":"Target internalization rate","max":1,"min":0,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.01,"unit":"1/h","value":0},{"category":"model parameter","definition":"Target synthesis rate governing production or formation in the modeled biological process.","description":"Target synthesis rate governing production or formation in the modeled biological process.","key":"ksyn_nM_h","label":"Target synthesis rate","max":9.864,"min":3.2880000000000003,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.01,"unit":"nM/h","value":6.5760000000000005}],"description":"How do route and dose change befovacimab exposure, free antibody, TFPI, and bound complex? Explore this biological starting configuration through Total central befovacimab, Free central befovacimab, Total TFPI, Befovacimab–TFPI complex, Cumulative exposure.","interpretation_guardrails":["Interpret trajectories as deterministic model behavior, not as a patient-specific prediction or dosing recommendation.","Paper-result and exact-anchor checks remain in the private validation lane and are not part of this public scenario."],"name":"human 0.4 mg/kg endpoints","outputs":[{"classification":"provisional","description":"Total central befovacimab over the selected simulation window.","key":"central_total_mg_L","label":"Total central befovacimab","unit":null},{"classification":"provisional","description":"Free central befovacimab over the selected simulation window.","key":"central_free_nM","label":"Free central befovacimab","unit":null},{"classification":"provisional","description":"Total target concentration over the selected simulation window.","key":"target_total_nM","label":"Total target concentration","unit":"nM"},{"classification":"provisional","description":"Befovacimab TFPI complex over the selected simulation window.","key":"complex_nM","label":"Befovacimab TFPI complex","unit":null},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_h_L","label":"Exposure (AUC)","unit":"mg*h/L"}],"scenario_id":"gu_2017_exploratory_calibrated_human_0p4mgkg_endpoints","scientific_questions":["How do route and dose change befovacimab exposure, free antibody, TFPI, and bound complex?"],"time_span":{"end":168,"start":0,"step":0.5}}],"targets":[{"key":"tfpi","label":"TFPI"},{"key":"tissue_factor_pathway_inhibitor","label":"tissue factor pathway inhibitor"}],"therapeutics":[{"key":"befovacimab","label":"Befovacimab"},{"key":"bay_1093884_befovacimab","label":"BAY 1093884 / befovacimab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.2.3"},{"availability":{"catalog_qualified":true,"released":true},"description":"Explore typical apparent erenumab exposure, six immune-cell states and explicitly dosed immunosuppressant projections.","diseases":[{"key":"preclinical_human_antibody_immunogenicity_and_tolerance","label":"Preclinical human-antibody immunogenicity and tolerance"}],"links":{"page":"/modeling/models/gupta-2025-erenumab-immune-tolerance-pkpd","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":null,"model_classes":["apparent one-compartment SC PK","six-cell immune projection","finite immunosuppressant kernels"],"model_id":"gupta_2025_erenumab_immune_tolerance_pkpd","name":"Erenumab exposure and immune tolerance in rats","outputs":[{"description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Monomer — no immunosuppression","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"group-1-1-monomer-no-immunosuppression","scientific_questions":["How do the model's key biological readouts change under monomer — no immunosuppression?"],"time_span":{"end":84,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Monomer — weekly MTX","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"group-1-2-monomer-mtx-weekly","scientific_questions":["How do the model's key biological readouts change under monomer — weekly mtx?"],"time_span":{"end":84,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Monomer — three-day MTX","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"group-1-3-monomer-mtx-three-day","scientific_questions":["How do the model's key biological readouts change under monomer — three-day mtx?"],"time_span":{"end":84,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Monomer — TAC/SIR projection","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"group-1-4-monomer-tac-sirolimus","scientific_questions":["How do the model's key biological readouts change under monomer — tac/sir projection?"],"time_span":{"end":84,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Aggregate — no immunosuppression","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"group-2-1-aggregate-no-immunosuppression","scientific_questions":["How do the model's key biological readouts change under aggregate — no immunosuppression?"],"time_span":{"end":84,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Aggregate — TAC/SIR projection","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"group-2-2-aggregate-tac-sirolimus","scientific_questions":["How do the model's key biological readouts change under aggregate — tac/sir projection?"],"time_span":{"end":84,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Authored chronic monomer — 52-week window","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"chronic-monomer-tac-sirolimus-rechallenge-6mo","scientific_questions":["How do the model's key biological readouts change under authored chronic monomer — 52-week window?"],"time_span":{"end":364,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Monomer — controlled observed S/N 1× cutoff","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"monomer-observed-sn-1x-threshold","scientific_questions":["How do the model's key biological readouts change under monomer — controlled observed s/n 1× cutoff?"],"time_span":{"end":84,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Monomer — controlled observed S/N 2× cutoff","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"monomer-observed-sn-2x-threshold","scientific_questions":["How do the model's key biological readouts change under monomer — controlled observed s/n 2× cutoff?"],"time_span":{"end":84,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Monomer — authored observed S/N steps","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"monomer-observed-sn-step-control","scientific_questions":["How do the model's key biological readouts change under monomer — authored observed s/n steps?"],"time_span":{"end":84,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Aggregate — controlled observed S/N 1× cutoff","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"aggregate-observed-sn-1x-threshold","scientific_questions":["How do the model's key biological readouts change under aggregate — controlled observed s/n 1× cutoff?"],"time_span":{"end":84,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Aggregate — controlled observed S/N 2× cutoff","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"aggregate-observed-sn-2x-threshold","scientific_questions":["How do the model's key biological readouts change under aggregate — controlled observed s/n 2× cutoff?"],"time_span":{"end":84,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Aggregate — authored observed S/N steps","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"aggregate-observed-sn-step-control","scientific_questions":["How do the model's key biological readouts change under aggregate — authored observed s/n steps?"],"time_span":{"end":84,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Drug-free immune baseline","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"drug-free-immune-baseline","scientific_questions":["How do the model's key biological readouts change under drug-free immune baseline?"],"time_span":{"end":84,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Fixed monomer input — 10 ug/mL","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"fixed-monomer-10ugml-immune-input","scientific_questions":["How do the model's key biological readouts change under fixed monomer input — 10 ug/ml?"],"time_span":{"end":84,"start":0,"step":0.5}},{"controls":[],"description":"Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.","interpretation_guardrails":["Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.","Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.","Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.","The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.","Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.","Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.","Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.","TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.","Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.","TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.","MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.","The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.","Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.","No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined."],"name":"Fixed aggregate input — 10 ug/mL","outputs":[{"classification":"provisional","description":"Serum over the selected simulation window.","key":"serum_ug_ml","label":"Serum","unit":"ug/mL"},{"classification":"provisional","description":"Ath over the selected simulation window.","key":"ath","label":"Ath","unit":"1/uL"},{"classification":"provisional","description":"Atr over the selected simulation window.","key":"atr","label":"Atr","unit":"1/uL"},{"classification":"provisional","description":"Model ada signal over the selected simulation window.","key":"model_ada_signal","label":"Model ada signal","unit":"dimensionless"}],"scenario_id":"fixed-aggregate-10ugml-immune-input","scientific_questions":["How do the model's key biological readouts change under fixed aggregate input — 10 ug/ml?"],"time_span":{"end":84,"start":0,"step":0.5}}],"targets":[{"key":"cgrp_receptor","label":"CGRP receptor","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.3390/pharmaceutics17070845","locator":"Primary-reference pharmacological or study context; authored card and source-review context.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"therapeutics":[{"key":"erenumab","label":"Erenumab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.1.0"},{"availability":{"catalog_qualified":true,"released":true},"description":"A mechanistic pharmacodynamic model connecting PROTAC concentration, target and E3-ligase binding, catalytic degradation, protein turnover, and the high-concentration hook effect.","diseases":[{"key":"mechanistic_target_degradation_pharmacology","label":"Mechanistic target-degradation pharmacology"}],"links":{"page":"/modeling/models/haid-2023-protac-mechanistic-pd-framework","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":null,"model_classes":["Other/Unclassified"],"model_id":"haid_2023_protac_mechanistic_pd_framework","name":"PROTAC target-engagement and degradation dynamics","outputs":[{"description":"Relative mechanistic degradation over the selected simulation window.","key":"p_mech_rel","label":"Relative mechanistic degradation","unit":"dimensionless"},{"description":"Relative hook-effect response over the selected simulation window.","key":"p_hook_rel","label":"Relative hook-effect response","unit":"dimensionless"},{"description":"Simplified target engagement over the selected simulation window.","key":"te_simplified","label":"Simplified target engagement","unit":null},{"description":"Steady state maximum degradation over the selected simulation window.","key":"hook_dmax_ss","label":"Steady state maximum degradation","unit":null},{"description":"Elapsed over the selected simulation window.","key":"elapsed_h","label":"Elapsed","unit":"h"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[{"category":"model parameter","definition":"PROTAC concentration coefficient used by the released system of model equations.","description":"PROTAC concentration coefficient used by the released system of model equations.","key":"protac_conc_nm","label":"PROTAC concentration","max":103.35000000000001,"min":34.45,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.1,"unit":"nM","value":68.9},{"category":"model parameter","definition":"Target–PROTAC dissociation constant describing equilibrium binding affinity in the modeled interaction.","description":"Target–PROTAC dissociation constant describing equilibrium binding affinity in the modeled interaction.","key":"kd_p_nm","label":"Target–PROTAC dissociation constant","max":207,"min":69,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"nM","value":138},{"category":"model parameter","definition":"PROTAC–E3 ligase dissociation constant describing equilibrium binding affinity in the modeled interaction.","description":"PROTAC–E3 ligase dissociation constant describing equilibrium binding affinity in the modeled interaction.","key":"kd_e_nm","label":"PROTAC–E3 ligase dissociation constant","max":4650,"min":1550,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":10,"unit":"nM","value":3100},{"category":"model parameter","definition":"Catalytic degradation rate coefficient used by the released system of model equations.","description":"Catalytic degradation rate coefficient used by the released system of model equations.","key":"kcat_h","label":"Catalytic degradation rate","max":0.75,"min":0.25,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.001,"unit":"1/h","value":0.5},{"category":"model parameter","definition":"Target-protein half-life controlling the time required for the corresponding quantity to decrease by half.","description":"Target-protein half-life controlling the time required for the corresponding quantity to decrease by half.","key":"t_half_p_h","label":"Target-protein half-life","max":67.5,"min":22.5,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.1,"unit":"h","value":45}],"description":"How do binding affinity, catalytic rate, and PROTAC concentration determine target degradation and the hook effect? Explore this biological starting configuration through Mechanistic relative target protein, Hook-model relative target protein, Simplified target engagement, Steady-state maximum degradation.","interpretation_guardrails":["Interpret trajectories as deterministic model behavior, not as a patient-specific prediction or dosing recommendation.","Paper-result and exact-anchor checks remain in the private validation lane and are not part of this public scenario."],"name":"Eq. 14 hook-model 6 h to 24 h RIPK2 degradation","outputs":[{"classification":"provisional","description":"Relative mechanistic degradation over the selected simulation window.","key":"p_mech_rel","label":"Relative mechanistic degradation","unit":"dimensionless"},{"classification":"provisional","description":"Relative hook-effect response over the selected simulation window.","key":"p_hook_rel","label":"Relative hook-effect response","unit":"dimensionless"},{"classification":"provisional","description":"Simplified target engagement over the selected simulation window.","key":"te_simplified","label":"Simplified target engagement","unit":null},{"classification":"provisional","description":"Steady state maximum degradation over the selected simulation window.","key":"hook_dmax_ss","label":"Steady state maximum degradation","unit":null}],"scenario_id":"mares_ripk2_hook_timecourse","scientific_questions":["How do binding affinity, catalytic rate, and PROTAC concentration determine target degradation and the hook effect?"],"time_span":{"end":96,"start":0,"step":1}},{"controls":[{"category":"model parameter","definition":"PROTAC concentration coefficient used by the released system of model equations.","description":"PROTAC concentration coefficient used by the released system of model equations.","key":"protac_conc_nm","label":"PROTAC concentration","max":150,"min":50,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"nM","value":100},{"category":"model parameter","definition":"Target–PROTAC dissociation constant describing equilibrium binding affinity in the modeled interaction.","description":"Target–PROTAC dissociation constant describing equilibrium binding affinity in the modeled interaction.","key":"kd_p_nm","label":"Target–PROTAC dissociation constant","max":207,"min":69,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"nM","value":138},{"category":"model parameter","definition":"PROTAC–E3 ligase dissociation constant describing equilibrium binding affinity in the modeled interaction.","description":"PROTAC–E3 ligase dissociation constant describing equilibrium binding affinity in the modeled interaction.","key":"kd_e_nm","label":"PROTAC–E3 ligase dissociation constant","max":4650,"min":1550,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":10,"unit":"nM","value":3100},{"category":"model parameter","definition":"Catalytic degradation rate coefficient used by the released system of model equations.","description":"Catalytic degradation rate coefficient used by the released system of model equations.","key":"kcat_h","label":"Catalytic degradation rate","max":0.75,"min":0.25,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.001,"unit":"1/h","value":0.5},{"category":"model parameter","definition":"Target-protein half-life controlling the time required for the corresponding quantity to decrease by half.","description":"Target-protein half-life controlling the time required for the corresponding quantity to decrease by half.","key":"t_half_p_h","label":"Target-protein half-life","max":24,"min":8,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.1,"unit":"h","value":16}],"description":"How do binding affinity, catalytic rate, and PROTAC concentration determine target degradation and the hook effect? Explore this biological starting configuration through Mechanistic relative target protein, Hook-model relative target protein, Simplified target engagement, Steady-state maximum degradation.","interpretation_guardrails":["Interpret trajectories as deterministic model behavior, not as a patient-specific prediction or dosing recommendation.","Paper-result and exact-anchor checks remain in the private validation lane and are not part of this public scenario."],"name":"Mechanistic Eq. 8 target-engagement degradation","outputs":[{"classification":"provisional","description":"Relative mechanistic degradation over the selected simulation window.","key":"p_mech_rel","label":"Relative mechanistic degradation","unit":"dimensionless"},{"classification":"provisional","description":"Relative hook-effect response over the selected simulation window.","key":"p_hook_rel","label":"Relative hook-effect response","unit":"dimensionless"},{"classification":"provisional","description":"Simplified target engagement over the selected simulation window.","key":"te_simplified","label":"Simplified target engagement","unit":null},{"classification":"provisional","description":"Steady state maximum degradation over the selected simulation window.","key":"hook_dmax_ss","label":"Steady state maximum degradation","unit":null}],"scenario_id":"ramos_cpd_i_mechanistic_te_ode","scientific_questions":["How do binding affinity, catalytic rate, and PROTAC concentration determine target degradation and the hook effect?"],"time_span":{"end":48,"start":0,"step":1}}],"targets":[{"key":"generic_poi","label":"generic POI"},{"key":"e3_ligase","label":"E3 ligase"}],"therapeutics":[{"key":"parameterized_protac","label":"Parameterized PROTAC"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.2.3"},{"availability":{"catalog_qualified":true,"released":true},"description":"Two-compartment physical PK realized from the authors' executed simulation code, with linear and time-declining saturable elimination on the central amount, explicit infusions and separate loss accounting.","diseases":[{"key":"multiple_myeloma_reference_pk","label":"Multiple myeloma reference PK"}],"links":{"page":"/modeling/models/han-2026-sim2real-pk-daratumumab-tmdd","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"monoclonal antibody","model_classes":["two-compartment IV PK","linear and time-declining saturable elimination"],"model_id":"han_2026_sim2real_pk_daratumumab_tmdd","name":"Daratumumab exposure and time-dependent clearance","outputs":[{"description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Single 4 mg/kg reference projection","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"single-dose-4mgkg-physical-pk","scientific_questions":["How do the model's key biological readouts change under single 4 mg/kg reference projection?"],"time_span":{"end":2,"start":0,"step":0.05}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Single 6 mg/kg reference projection","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"single-dose-6mgkg-physical-pk","scientific_questions":["How do the model's key biological readouts change under single 6 mg/kg reference projection?"],"time_span":{"end":2,"start":0,"step":0.05}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Single 8 mg/kg reference projection","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"single-dose-8mgkg-physical-pk","scientific_questions":["How do the model's key biological readouts change under single 8 mg/kg reference projection?"],"time_span":{"end":2,"start":0,"step":0.05}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Single 10 mg/kg reference projection","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"single-dose-10mgkg-physical-pk","scientific_questions":["How do the model's key biological readouts change under single 10 mg/kg reference projection?"],"time_span":{"end":2,"start":0,"step":0.05}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Single 12 mg/kg reference projection","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"single-dose-12mgkg-physical-pk","scientific_questions":["How do the model's key biological readouts change under single 12 mg/kg reference projection?"],"time_span":{"end":2,"start":0,"step":0.05}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Single 14 mg/kg reference projection","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"single-dose-14mgkg-physical-pk","scientific_questions":["How do the model's key biological readouts change under single 14 mg/kg reference projection?"],"time_span":{"end":2,"start":0,"step":0.05}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Single 16 mg/kg reference projection","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"single-dose-16mgkg-ode-dose-exposure-anchor","scientific_questions":["How do the model's key biological readouts change under single 16 mg/kg reference projection?"],"time_span":{"end":2,"start":0,"step":0.05}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Single 18 mg/kg reference projection","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"single-dose-18mgkg-physical-pk","scientific_questions":["How do the model's key biological readouts change under single 18 mg/kg reference projection?"],"time_span":{"end":2,"start":0,"step":0.05}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Single 20 mg/kg reference projection","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"single-dose-20mgkg-physical-pk","scientific_questions":["How do the model's key biological readouts change under single 20 mg/kg reference projection?"],"time_span":{"end":2,"start":0,"step":0.05}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Albumin 20 g/L — 16 mg/kg short window","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"albumin-20-16mgkg-short-window","scientific_questions":["How do the model's key biological readouts change under albumin 20 g/l — 16 mg/kg short window?"],"time_span":{"end":14,"start":0,"step":0.1}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Albumin 25 g/L — 16 mg/kg short window","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"low-albumin-16mgkg-covariate-ode-overlay","scientific_questions":["How do the model's key biological readouts change under albumin 25 g/l — 16 mg/kg short window?"],"time_span":{"end":14,"start":0,"step":0.1}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Albumin 37 g/L — 16 mg/kg short window","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"label-like-16mgkg-window-ode-overlay","scientific_questions":["How do the model's key biological readouts change under albumin 37 g/l — 16 mg/kg short window?"],"time_span":{"end":14,"start":0,"step":0.1}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Albumin 50 g/L — 16 mg/kg short window","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"albumin-50-16mgkg-short-window","scientific_questions":["How do the model's key biological readouts change under albumin 50 g/l — 16 mg/kg short window?"],"time_span":{"end":14,"start":0,"step":0.1}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Female","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"female-16mgkg-short-window","scientific_questions":["How do the model's key biological readouts change under female?"],"time_span":{"end":14,"start":0,"step":0.1}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Igg myeloma","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"igg-myeloma-16mgkg-short-window","scientific_questions":["How do the model's key biological readouts change under igg myeloma?"],"time_span":{"end":14,"start":0,"step":0.1}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Weight 50kg","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"weight-50kg-16mgkg-short-window","scientific_questions":["How do the model's key biological readouts change under weight 50kg?"],"time_span":{"end":14,"start":0,"step":0.1}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Weight 100kg","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"weight-100kg-16mgkg-short-window","scientific_questions":["How do the model's key biological readouts change under weight 100kg?"],"time_span":{"end":14,"start":0,"step":0.1}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Authored 7/14/21-day phase calendar","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"phase-interval-16mgkg-1000day-projection","scientific_questions":["How do the model's key biological readouts change under authored 7/14/21-day phase calendar?"],"time_span":{"end":1000,"start":0,"step":2}},{"controls":[],"description":"Conditional physical PK projection with fixed covariates and explicitly authored administrations.","interpretation_guardrails":["Physical PK realization of the authors' executed simulation code: two compartments, linear loss and a time-declining saturable elimination applied to the central amount, with time in days, amounts mg and concentrations mg/L.","The supplied coefficient realization uses CL = .1 L/day, Q = 1.54 L/day, VM0 = 49.92 mg/day and kdes = .0312/day. These are model inputs, not newly estimated clinical parameters.","Saturable elimination is VM0 exp(-kdes elapsed) Acentral/(KM+Acentral), with KM = 0.93 mg applied to the central amount. This is a conditional executed-code coefficient realization; no explicit receptor or occupancy states are present.","Covariates are fixed, individual deviations and residual noise are zero. Dose amounts and weight are frozen together in each context.","First, second and later infusion durations are 7 h, 4.3 h and 3.4 h. Nominal calendars and split-first-dose examples are authored fixed realizations, without random jitter or synthetic cohort replay.","Short 14-day windows end predose at the day 14 administration; an infusion beginning at the endpoint contributes no exposure within that window.","Elapsed treatment time starts at zero. Shifted starts require a consistent prior drug history and treatment-clock initialization.","Neural training, fine-tuned patient prediction, optimized dosing, original clinical data and reported neural performance are not reconstructed.","A saturation rate factor is not CD38 receptor occupancy or an independently validated clinical target."],"name":"Authored split first dose — two 8 mg/kg infusions","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Exposure (AUC) over the selected simulation window.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Maximum elimination rate over the selected simulation window.","key":"vmax_mg_day","label":"Maximum elimination rate","unit":"mg/day"},{"classification":"provisional","description":"Total eliminated over the selected simulation window.","key":"total_eliminated_mg","label":"Total eliminated","unit":"mg"}],"scenario_id":"split-first-16mgkg-projection","scientific_questions":["How do the model's key biological readouts change under authored split first dose — two 8 mg/kg infusions?"],"time_span":{"end":28,"start":0,"step":0.25}}],"targets":[{"key":"cd38","label":"CD38","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.21203/rs.3.rs-9308510/v1","locator":"Primary-reference pharmacological or study context; authored card and source-review context.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"therapeutics":[{"key":"daratumumab","label":"Daratumumab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.2.2"},{"availability":{"catalog_qualified":true,"released":true},"description":"A deterministic two-compartment FVIII activity implementation for exploring age, body weight, blood group, surgery category and assay observation conventions.","diseases":[{"key":"hemophilia_a_perioperative_fviii_activity","label":"Hemophilia A; perioperative FVIII activity"}],"links":{"page":"/modeling/models/hazendonk-2016-perioperative-fviii-literature","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":null,"model_classes":["Other/Unclassified"],"model_id":"hazendonk_2016_perioperative_fviii_literature","name":"FVIII activity distribution and perioperative covariates","outputs":[{"description":"Exogenous iu over the selected simulation window.","key":"exogenous_IU_mL","label":"Exogenous iu","unit":"IU/mL"},{"description":"Selected assay iu over the selected simulation window.","key":"selected_assay_IU_mL","label":"Selected assay iu","unit":"IU/mL"},{"description":"AUC exogenous over the selected simulation window.","key":"AUC_exogenous","label":"AUC exogenous","unit":"IU*hour/mL"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"An authored deterministic FVIII activity experiment.","interpretation_guardrails":["FVIII amounts are international biological activity units (IU); concentrations are IU/mL. No mass or generic enzyme-unit conversion is implied.","Doses and covariates in these examples are synthetic research inputs, not patient records or dosing recommendations.","The B-domain-deleted assay factor changes the observation only. Endogenous baseline is an observation input and contributes no administered drug.","Alternative placements of baseline in the assay correction remain separate conditional conventions.","Reported coefficients are used without re-estimation. Subject-effect and residual-error observers are explicit conditional completions; the original statistical fit is not reproduced.","This model does not predict bleeding, coagulation, VWF binding or extended-half-life product behavior, and does not implement adaptive dosing."],"name":"68 kg, 40 years: blood group O absent, minor surgery","outputs":[{"classification":"provisional","description":"Exogenous iu over the selected simulation window.","key":"exogenous_IU_mL","label":"Exogenous iu","unit":"IU/mL"},{"classification":"provisional","description":"Selected assay iu over the selected simulation window.","key":"selected_assay_IU_mL","label":"Selected assay iu","unit":"IU/mL"},{"classification":"provisional","description":"AUC exogenous over the selected simulation window.","key":"AUC_exogenous","label":"AUC exogenous","unit":"IU*hour/mL"}],"scenario_id":"activity_o0_major0","scientific_questions":["How do the model's key biological readouts change under 68 kg, 40 years: blood group o absent, minor surgery?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"An authored deterministic FVIII activity experiment.","interpretation_guardrails":["FVIII amounts are international biological activity units (IU); concentrations are IU/mL. No mass or generic enzyme-unit conversion is implied.","Doses and covariates in these examples are synthetic research inputs, not patient records or dosing recommendations.","The B-domain-deleted assay factor changes the observation only. Endogenous baseline is an observation input and contributes no administered drug.","Alternative placements of baseline in the assay correction remain separate conditional conventions.","Reported coefficients are used without re-estimation. Subject-effect and residual-error observers are explicit conditional completions; the original statistical fit is not reproduced.","This model does not predict bleeding, coagulation, VWF binding or extended-half-life product behavior, and does not implement adaptive dosing."],"name":"68 kg, 40 years: blood group O absent, major surgery","outputs":[{"classification":"provisional","description":"Exogenous iu over the selected simulation window.","key":"exogenous_IU_mL","label":"Exogenous iu","unit":"IU/mL"},{"classification":"provisional","description":"Selected assay iu over the selected simulation window.","key":"selected_assay_IU_mL","label":"Selected assay iu","unit":"IU/mL"},{"classification":"provisional","description":"AUC exogenous over the selected simulation window.","key":"AUC_exogenous","label":"AUC exogenous","unit":"IU*hour/mL"}],"scenario_id":"activity_o0_major1","scientific_questions":["How do the model's key biological readouts change under 68 kg, 40 years: blood group o absent, major surgery?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"An authored deterministic FVIII activity experiment.","interpretation_guardrails":["FVIII amounts are international biological activity units (IU); concentrations are IU/mL. No mass or generic enzyme-unit conversion is implied.","Doses and covariates in these examples are synthetic research inputs, not patient records or dosing recommendations.","The B-domain-deleted assay factor changes the observation only. Endogenous baseline is an observation input and contributes no administered drug.","Alternative placements of baseline in the assay correction remain separate conditional conventions.","Reported coefficients are used without re-estimation. Subject-effect and residual-error observers are explicit conditional completions; the original statistical fit is not reproduced.","This model does not predict bleeding, coagulation, VWF binding or extended-half-life product behavior, and does not implement adaptive dosing."],"name":"68 kg, 40 years: blood group O present, minor surgery","outputs":[{"classification":"provisional","description":"Exogenous iu over the selected simulation window.","key":"exogenous_IU_mL","label":"Exogenous iu","unit":"IU/mL"},{"classification":"provisional","description":"Selected assay iu over the selected simulation window.","key":"selected_assay_IU_mL","label":"Selected assay iu","unit":"IU/mL"},{"classification":"provisional","description":"AUC exogenous over the selected simulation window.","key":"AUC_exogenous","label":"AUC exogenous","unit":"IU*hour/mL"}],"scenario_id":"activity_o1_major0","scientific_questions":["How do the model's key biological readouts change under 68 kg, 40 years: blood group o present, minor surgery?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"An authored deterministic FVIII activity experiment.","interpretation_guardrails":["FVIII amounts are international biological activity units (IU); concentrations are IU/mL. No mass or generic enzyme-unit conversion is implied.","Doses and covariates in these examples are synthetic research inputs, not patient records or dosing recommendations.","The B-domain-deleted assay factor changes the observation only. Endogenous baseline is an observation input and contributes no administered drug.","Alternative placements of baseline in the assay correction remain separate conditional conventions.","Reported coefficients are used without re-estimation. Subject-effect and residual-error observers are explicit conditional completions; the original statistical fit is not reproduced.","This model does not predict bleeding, coagulation, VWF binding or extended-half-life product behavior, and does not implement adaptive dosing."],"name":"68 kg, 40 years: blood group O present, major surgery","outputs":[{"classification":"provisional","description":"Exogenous iu over the selected simulation window.","key":"exogenous_IU_mL","label":"Exogenous iu","unit":"IU/mL"},{"classification":"provisional","description":"Selected assay iu over the selected simulation window.","key":"selected_assay_IU_mL","label":"Selected assay iu","unit":"IU/mL"},{"classification":"provisional","description":"AUC exogenous over the selected simulation window.","key":"AUC_exogenous","label":"AUC exogenous","unit":"IU*hour/mL"}],"scenario_id":"activity_o1_major1","scientific_questions":["How do the model's key biological readouts change under 68 kg, 40 years: blood group o present, major surgery?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"An authored deterministic FVIII activity experiment.","interpretation_guardrails":["FVIII amounts are international biological activity units (IU); concentrations are IU/mL. No mass or generic enzyme-unit conversion is implied.","Doses and covariates in these examples are synthetic research inputs, not patient records or dosing recommendations.","The B-domain-deleted assay factor changes the observation only. Endogenous baseline is an observation input and contributes no administered drug.","Alternative placements of baseline in the assay correction remain separate conditional conventions.","Reported coefficients are used without re-estimation. Subject-effect and residual-error observers are explicit conditional completions; the original statistical fit is not reproduced.","This model does not predict bleeding, coagulation, VWF binding or extended-half-life product behavior, and does not implement adaptive dosing."],"name":"Age 5 years at 68 kg: activity over 24 hours","outputs":[{"classification":"provisional","description":"Exogenous iu over the selected simulation window.","key":"exogenous_IU_mL","label":"Exogenous iu","unit":"IU/mL"},{"classification":"provisional","description":"Selected assay iu over the selected simulation window.","key":"selected_assay_IU_mL","label":"Selected assay iu","unit":"IU/mL"},{"classification":"provisional","description":"AUC exogenous over the selected simulation window.","key":"AUC_exogenous","label":"AUC exogenous","unit":"IU*hour/mL"}],"scenario_id":"age_5_years","scientific_questions":["How do the model's key biological readouts change under age 5 years at 68 kg: activity over 24 hours?"],"time_span":{"end":24,"start":0,"step":1}},{"controls":[],"description":"An authored deterministic FVIII activity experiment.","interpretation_guardrails":["FVIII amounts are international biological activity units (IU); concentrations are IU/mL. No mass or generic enzyme-unit conversion is implied.","Doses and covariates in these examples are synthetic research inputs, not patient records or dosing recommendations.","The B-domain-deleted assay factor changes the observation only. Endogenous baseline is an observation input and contributes no administered drug.","Alternative placements of baseline in the assay correction remain separate conditional conventions.","Reported coefficients are used without re-estimation. Subject-effect and residual-error observers are explicit conditional completions; the original statistical fit is not reproduced.","This model does not predict bleeding, coagulation, VWF binding or extended-half-life product behavior, and does not implement adaptive dosing."],"name":"Age 20 years at 68 kg: activity over 24 hours","outputs":[{"classification":"provisional","description":"Exogenous iu over the selected simulation window.","key":"exogenous_IU_mL","label":"Exogenous iu","unit":"IU/mL"},{"classification":"provisional","description":"Selected assay iu over the selected simulation window.","key":"selected_assay_IU_mL","label":"Selected assay iu","unit":"IU/mL"},{"classification":"provisional","description":"AUC exogenous over the selected simulation window.","key":"AUC_exogenous","label":"AUC exogenous","unit":"IU*hour/mL"}],"scenario_id":"age_20_years","scientific_questions":["How do the model's key biological readouts change under age 20 years at 68 kg: activity over 24 hours?"],"time_span":{"end":24,"start":0,"step":1}},{"controls":[],"description":"An authored deterministic FVIII activity experiment.","interpretation_guardrails":["FVIII amounts are international biological activity units (IU); concentrations are IU/mL. No mass or generic enzyme-unit conversion is implied.","Doses and covariates in these examples are synthetic research inputs, not patient records or dosing recommendations.","The B-domain-deleted assay factor changes the observation only. Endogenous baseline is an observation input and contributes no administered drug.","Alternative placements of baseline in the assay correction remain separate conditional conventions.","Reported coefficients are used without re-estimation. Subject-effect and residual-error observers are explicit conditional completions; the original statistical fit is not reproduced.","This model does not predict bleeding, coagulation, VWF binding or extended-half-life product behavior, and does not implement adaptive dosing."],"name":"Age 40 years at 68 kg: activity over 24 hours","outputs":[{"classification":"provisional","description":"Exogenous iu over the selected simulation window.","key":"exogenous_IU_mL","label":"Exogenous iu","unit":"IU/mL"},{"classification":"provisional","description":"Selected assay iu over the selected simulation window.","key":"selected_assay_IU_mL","label":"Selected assay iu","unit":"IU/mL"},{"classification":"provisional","description":"AUC exogenous over the selected simulation window.","key":"AUC_exogenous","label":"AUC exogenous","unit":"IU*hour/mL"}],"scenario_id":"age_40_years","scientific_questions":["How do the model's key biological readouts change under age 40 years at 68 kg: activity over 24 hours?"],"time_span":{"end":24,"start":0,"step":1}},{"controls":[],"description":"An authored deterministic FVIII activity experiment.","interpretation_guardrails":["FVIII amounts are international biological activity units (IU); concentrations are IU/mL. No mass or generic enzyme-unit conversion is implied.","Doses and covariates in these examples are synthetic research inputs, not patient records or dosing recommendations.","The B-domain-deleted assay factor changes the observation only. Endogenous baseline is an observation input and contributes no administered drug.","Alternative placements of baseline in the assay correction remain separate conditional conventions.","Reported coefficients are used without re-estimation. Subject-effect and residual-error observers are explicit conditional completions; the original statistical fit is not reproduced.","This model does not predict bleeding, coagulation, VWF binding or extended-half-life product behavior, and does not implement adaptive dosing."],"name":"Age 55 years at 68 kg: activity over 24 hours","outputs":[{"classification":"provisional","description":"Exogenous iu over the selected simulation window.","key":"exogenous_IU_mL","label":"Exogenous iu","unit":"IU/mL"},{"classification":"provisional","description":"Selected assay iu over the selected simulation window.","key":"selected_assay_IU_mL","label":"Selected assay iu","unit":"IU/mL"},{"classification":"provisional","description":"AUC exogenous over the selected simulation window.","key":"AUC_exogenous","label":"AUC exogenous","unit":"IU*hour/mL"}],"scenario_id":"age_55_years","scientific_questions":["How do the model's key biological readouts change under age 55 years at 68 kg: activity over 24 hours?"],"time_span":{"end":24,"start":0,"step":1}},{"controls":[],"description":"An authored deterministic FVIII activity experiment.","interpretation_guardrails":["FVIII amounts are international biological activity units (IU); concentrations are IU/mL. No mass or generic enzyme-unit conversion is implied.","Doses and covariates in these examples are synthetic research inputs, not patient records or dosing recommendations.","The B-domain-deleted assay factor changes the observation only. Endogenous baseline is an observation input and contributes no administered drug.","Alternative placements of baseline in the assay correction remain separate conditional conventions.","Reported coefficients are used without re-estimation. Subject-effect and residual-error observers are explicit conditional completions; the original statistical fit is not reproduced.","This model does not predict bleeding, coagulation, VWF binding or extended-half-life product behavior, and does not implement adaptive dosing."],"name":"Three repeated activity inputs at 24-hour intervals","outputs":[{"classification":"provisional","description":"Exogenous iu over the selected simulation window.","key":"exogenous_IU_mL","label":"Exogenous iu","unit":"IU/mL"},{"classification":"provisional","description":"Selected assay iu over the selected simulation window.","key":"selected_assay_IU_mL","label":"Selected assay iu","unit":"IU/mL"},{"classification":"provisional","description":"AUC exogenous over the selected simulation window.","key":"AUC_exogenous","label":"AUC exogenous","unit":"IU*hour/mL"}],"scenario_id":"repeat_activity_inputs","scientific_questions":["How do the model's key biological readouts change under three repeated activity inputs at 24-hour intervals?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"An authored deterministic FVIII activity experiment.","interpretation_guardrails":["FVIII amounts are international biological activity units (IU); concentrations are IU/mL. No mass or generic enzyme-unit conversion is implied.","Doses and covariates in these examples are synthetic research inputs, not patient records or dosing recommendations.","The B-domain-deleted assay factor changes the observation only. Endogenous baseline is an observation input and contributes no administered drug.","Alternative placements of baseline in the assay correction remain separate conditional conventions.","Reported coefficients are used without re-estimation. Subject-effect and residual-error observers are explicit conditional completions; the original statistical fit is not reproduced.","This model does not predict bleeding, coagulation, VWF binding or extended-half-life product behavior, and does not implement adaptive dosing."],"name":"Overlapping infusions with a bolus","outputs":[{"classification":"provisional","description":"Exogenous iu over the selected simulation window.","key":"exogenous_IU_mL","label":"Exogenous iu","unit":"IU/mL"},{"classification":"provisional","description":"Selected assay iu over the selected simulation window.","key":"selected_assay_IU_mL","label":"Selected assay iu","unit":"IU/mL"},{"classification":"provisional","description":"AUC exogenous over the selected simulation window.","key":"AUC_exogenous","label":"AUC exogenous","unit":"IU*hour/mL"}],"scenario_id":"overlapping_activity_inputs","scientific_questions":["How do the model's key biological readouts change under overlapping infusions with a bolus?"],"time_span":{"end":48,"start":0,"step":1}},{"controls":[],"description":"An authored deterministic FVIII activity experiment.","interpretation_guardrails":["FVIII amounts are international biological activity units (IU); concentrations are IU/mL. No mass or generic enzyme-unit conversion is implied.","Doses and covariates in these examples are synthetic research inputs, not patient records or dosing recommendations.","The B-domain-deleted assay factor changes the observation only. Endogenous baseline is an observation input and contributes no administered drug.","Alternative placements of baseline in the assay correction remain separate conditional conventions.","Reported coefficients are used without re-estimation. Subject-effect and residual-error observers are explicit conditional completions; the original statistical fit is not reproduced.","This model does not predict bleeding, coagulation, VWF binding or extended-half-life product behavior, and does not implement adaptive dosing."],"name":"Endogenous baseline included before assay correction","outputs":[{"classification":"provisional","description":"Exogenous iu over the selected simulation window.","key":"exogenous_IU_mL","label":"Exogenous iu","unit":"IU/mL"},{"classification":"provisional","description":"Selected assay iu over the selected simulation window.","key":"selected_assay_IU_mL","label":"Selected assay iu","unit":"IU/mL"},{"classification":"provisional","description":"AUC exogenous over the selected simulation window.","key":"AUC_exogenous","label":"AUC exogenous","unit":"IU*hour/mL"}],"scenario_id":"baseline_before_assay","scientific_questions":["How do the model's key biological readouts change under endogenous baseline included before assay correction?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"An authored deterministic FVIII activity experiment.","interpretation_guardrails":["FVIII amounts are international biological activity units (IU); concentrations are IU/mL. No mass or generic enzyme-unit conversion is implied.","Doses and covariates in these examples are synthetic research inputs, not patient records or dosing recommendations.","The B-domain-deleted assay factor changes the observation only. Endogenous baseline is an observation input and contributes no administered drug.","Alternative placements of baseline in the assay correction remain separate conditional conventions.","Reported coefficients are used without re-estimation. Subject-effect and residual-error observers are explicit conditional completions; the original statistical fit is not reproduced.","This model does not predict bleeding, coagulation, VWF binding or extended-half-life product behavior, and does not implement adaptive dosing."],"name":"Endogenous baseline included after exogenous assay correction","outputs":[{"classification":"provisional","description":"Exogenous iu over the selected simulation window.","key":"exogenous_IU_mL","label":"Exogenous iu","unit":"IU/mL"},{"classification":"provisional","description":"Selected assay iu over the selected simulation window.","key":"selected_assay_IU_mL","label":"Selected assay iu","unit":"IU/mL"},{"classification":"provisional","description":"AUC exogenous over the selected simulation window.","key":"AUC_exogenous","label":"AUC exogenous","unit":"IU*hour/mL"}],"scenario_id":"baseline_after_assay","scientific_questions":["How do the model's key biological readouts change under endogenous baseline included after exogenous assay correction?"],"time_span":{"end":168,"start":0,"step":1}}],"targets":[{"key":"factor_viii_activity","label":"Factor VIII activity","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.3324/haematol.2015.136275","locator":"Primary-reference pharmacological or study context; authored card and source-review context.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"therapeutics":[{"key":"factor_viii","label":"Factor VIII"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.1.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"Compare intravenous infliximab exposure during pediatric induction in the released reference cases. A two-compartment model uses fixed baseline covariates and tracks cumulative exposure.","diseases":[{"key":"pediatric_inflammatory_bowel_disease","label":"Pediatric inflammatory bowel disease"}],"links":{"page":"/modeling/models/hemperly-2025-infliximab-pediatric-ibd-poc-pk-er","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"monoclonal antibody","model_classes":["two-compartment IV PK","reference-parameter projection"],"model_id":"hemperly_2025_infliximab_pediatric_ibd_poc_pk_er","name":"Infliximab exposure during pediatric induction","outputs":[{"description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"clearance_l_day","label":"Clearance","unit":"L/day"},{"description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Conditional fixed-parameter IV exposure; nominal administrations, not individual patient data.","interpretation_guardrails":["Conditional typical-parameter pediatric induction PK; no observed cohort curve, individual prediction or clinical-response probability is reproduced.","Reference weight is 51.2 kg and albumin 4.2 g/dL. Central-volume convention uses the reported final estimate 3.43 L.","Weight is held at the administration reference in the default interactive contexts. Amounts are fixed at 256 or 512 mg; another weight requires explicit dose recalculation.","Days 0, 14 and 42 and two-hour infusions are declared nominal scenario conventions, not a common published patient event array.","Use predose sides for day 14 and day 42 troughs. Observer integrals do not introduce clinical-response dynamics.","The low-albumin context is a marginal baseline IQR endpoint, not a clinical threshold or an observed joint patient.","Original random-effect draws, statistical fitting, VPCs and patient-level assay comparisons are not reconstructed."],"name":"Standard 5mgkg induction typical full ode","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"clearance_l_day","label":"Clearance","unit":"L/day"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"standard-5mgkg-induction-typical-full-ode","scientific_questions":["How do the model's key biological readouts change under standard 5mgkg induction typical full ode?"],"time_span":{"end":98,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-parameter IV exposure; nominal administrations, not individual patient data.","interpretation_guardrails":["Conditional typical-parameter pediatric induction PK; no observed cohort curve, individual prediction or clinical-response probability is reproduced.","Reference weight is 51.2 kg and albumin 4.2 g/dL. Central-volume convention uses the reported final estimate 3.43 L.","Weight is held at the administration reference in the default interactive contexts. Amounts are fixed at 256 or 512 mg; another weight requires explicit dose recalculation.","Days 0, 14 and 42 and two-hour infusions are declared nominal scenario conventions, not a common published patient event array.","Use predose sides for day 14 and day 42 troughs. Observer integrals do not introduce clinical-response dynamics.","The low-albumin context is a marginal baseline IQR endpoint, not a clinical threshold or an observed joint patient.","Original random-effect draws, statistical fitting, VPCs and patient-level assay comparisons are not reconstructed."],"name":"Low albumin 5mgkg induction full ode","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"clearance_l_day","label":"Clearance","unit":"L/day"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"low-albumin-5mgkg-induction-full-ode","scientific_questions":["How do the model's key biological readouts change under low albumin 5mgkg induction full ode?"],"time_span":{"end":98,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-parameter IV exposure; nominal administrations, not individual patient data.","interpretation_guardrails":["Conditional typical-parameter pediatric induction PK; no observed cohort curve, individual prediction or clinical-response probability is reproduced.","Reference weight is 51.2 kg and albumin 4.2 g/dL. Central-volume convention uses the reported final estimate 3.43 L.","Weight is held at the administration reference in the default interactive contexts. Amounts are fixed at 256 or 512 mg; another weight requires explicit dose recalculation.","Days 0, 14 and 42 and two-hour infusions are declared nominal scenario conventions, not a common published patient event array.","Use predose sides for day 14 and day 42 troughs. Observer integrals do not introduce clinical-response dynamics.","The low-albumin context is a marginal baseline IQR endpoint, not a clinical threshold or an observed joint patient.","Original random-effect draws, statistical fitting, VPCs and patient-level assay comparisons are not reconstructed."],"name":"Intensified 10mgkg induction exploratory full ode","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"clearance_l_day","label":"Clearance","unit":"L/day"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"intensified-10mgkg-induction-exploratory-full-ode","scientific_questions":["How do the model's key biological readouts change under intensified 10mgkg induction exploratory full ode?"],"time_span":{"end":98,"start":0,"step":1}}],"targets":[{"key":"tnf","label":"TNF","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.3390/jcm14227968","locator":"Primary-reference pharmacological or study context; authored card and source-review context.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"therapeutics":[{"key":"infliximab","label":"Infliximab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.1.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"Apparent subcutaneous MEDI7836 exposure drives IL13 turnover and reversible complex formation. Free cytokine and a detected complex fraction contribute to a conditional mixed assay signal.","diseases":[{"key":"healthy_adult_volunteers","label":"healthy adult volunteers"}],"links":{"page":"/modeling/models/hood-2021-medi7836-conditional-source-reference","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"IgG1 lambda antibody with YTE Fc","model_classes":["Other/Unclassified"],"model_id":"hood_2021_medi7836_conditional_source_reference","name":"Antibody exposure and mixed IL13 assay signal","outputs":[{"description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"drug_serum","label":"Drug serum","unit":"nmol/L"},{"description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"target_free","label":"Target free","unit":"nmol/L"},{"description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"complex_serum","label":"Complex serum","unit":"nmol/L"},{"description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"assay_signal","label":"Assay signal","unit":"nmol/L"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[{"category":"Antibody clearance","definition":"Effective CL/F after the selected fixed ADA context. Exploratory 0.5–1.5× retained extrema; changing it does not re-estimate ADA status. Initial target and volumes remain fixed.","description":"Effective CL/F after the selected fixed ADA context. Exploratory 0.5–1.5× retained extrema; changing it does not re-estimate ADA status. Initial target and volumes remain fixed.","key":"cl","label":"Systemic clearance","max":1.1357955,"min":0.218936,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.001,"unit":"L/d","value":0.441}],"description":"How do free cytokine and mixed assay signal respond to fixed subcutaneous exposure and clearance?","interpretation_guardrails":["Conditional fixed-effect single-dose exploration in healthy adult volunteers; no clinical dosing, efficacy, safety, original population or patient-level prediction.","Apparent drug PK is an independent linear driver. Complex formation does not subtract central drug; the drug-driver ledger is not total chemical antibody conservation.","This implementation uses separate kinetic and observation volumes for the complex. The main coefficient vector gives an untreated assay-signal baseline of approximately 0.034 pM. These are conditional source-vector calculations; original population observations are not reconstructed.","The main bootstrap-median vector and two printed SI starting/fixed vectors remain separate. Initial target is kin/kout. All context parameters except effective apparent clearance stay fixed.","The ADA configurations apply the reported fixed clearance shift once. Editing effective clearance is an exploratory coefficient change, not an ADA-status or population estimate.","Clearance bounds are authored 0.5–1.5× the extrema of the retained effective clearances. They are exploratory bounds, not confidence intervals or clinical limits.","Changing the simulation start uses the supplied initial state at that start and does not reconstruct earlier doses. The declared dose observation sides remain explicit.","No source figure panel, population fit, residual likelihood, repeated-dose prediction or original patient observations are reproduced. Fitting and normal server scans are unavailable."],"name":"Fixed 30 mg exposure","outputs":[{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"drug_serum","label":"Drug serum","unit":"nmol/L"},{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"target_free","label":"Target free","unit":"nmol/L"},{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"complex_serum","label":"Complex serum","unit":"nmol/L"},{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"assay_signal","label":"Assay signal","unit":"nmol/L"}],"scenario_id":"main_bootstrap_original_SI_30mg_ADA0","scientific_questions":["How do free cytokine and mixed assay signal respond to fixed subcutaneous exposure and clearance?"],"time_span":{"end":280,"start":0,"step":1}},{"controls":[{"category":"Antibody clearance","definition":"Effective CL/F after the selected fixed ADA context. 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Complex formation does not subtract central drug; the drug-driver ledger is not total chemical antibody conservation.","This implementation uses separate kinetic and observation volumes for the complex. The main coefficient vector gives an untreated assay-signal baseline of approximately 0.034 pM. These are conditional source-vector calculations; original population observations are not reconstructed.","The main bootstrap-median vector and two printed SI starting/fixed vectors remain separate. Initial target is kin/kout. All context parameters except effective apparent clearance stay fixed.","The ADA configurations apply the reported fixed clearance shift once. Editing effective clearance is an exploratory coefficient change, not an ADA-status or population estimate.","Clearance bounds are authored 0.5–1.5× the extrema of the retained effective clearances. They are exploratory bounds, not confidence intervals or clinical limits.","Changing the simulation start uses the supplied initial state at that start and does not reconstruct earlier doses. The declared dose observation sides remain explicit.","No source figure panel, population fit, residual likelihood, repeated-dose prediction or original patient observations are reproduced. Fitting and normal server scans are unavailable."],"name":"Fixed 105 mg exposure","outputs":[{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"drug_serum","label":"Drug serum","unit":"nmol/L"},{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"target_free","label":"Target free","unit":"nmol/L"},{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"complex_serum","label":"Complex serum","unit":"nmol/L"},{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"assay_signal","label":"Assay signal","unit":"nmol/L"}],"scenario_id":"main_bootstrap_original_SI_105mg_ADA0","scientific_questions":["How do free cytokine and mixed assay signal respond to fixed subcutaneous exposure and clearance?"],"time_span":{"end":280,"start":0,"step":1}},{"controls":[{"category":"Antibody clearance","definition":"Effective CL/F after the selected fixed ADA context. 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Complex formation does not subtract central drug; the drug-driver ledger is not total chemical antibody conservation.","This implementation uses separate kinetic and observation volumes for the complex. The main coefficient vector gives an untreated assay-signal baseline of approximately 0.034 pM. These are conditional source-vector calculations; original population observations are not reconstructed.","The main bootstrap-median vector and two printed SI starting/fixed vectors remain separate. Initial target is kin/kout. All context parameters except effective apparent clearance stay fixed.","The ADA configurations apply the reported fixed clearance shift once. Editing effective clearance is an exploratory coefficient change, not an ADA-status or population estimate.","Clearance bounds are authored 0.5–1.5× the extrema of the retained effective clearances. They are exploratory bounds, not confidence intervals or clinical limits.","Changing the simulation start uses the supplied initial state at that start and does not reconstruct earlier doses. The declared dose observation sides remain explicit.","No source figure panel, population fit, residual likelihood, repeated-dose prediction or original patient observations are reproduced. Fitting and normal server scans are unavailable."],"name":"Fixed 300 mg exposure","outputs":[{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"drug_serum","label":"Drug serum","unit":"nmol/L"},{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"target_free","label":"Target free","unit":"nmol/L"},{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"complex_serum","label":"Complex serum","unit":"nmol/L"},{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"assay_signal","label":"Assay signal","unit":"nmol/L"}],"scenario_id":"main_bootstrap_original_SI_300mg_ADA0","scientific_questions":["How do free cytokine and mixed assay signal respond to fixed subcutaneous exposure and clearance?"],"time_span":{"end":280,"start":0,"step":1}},{"controls":[{"category":"Antibody clearance","definition":"Effective CL/F after the selected fixed ADA context. 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Complex formation does not subtract central drug; the drug-driver ledger is not total chemical antibody conservation.","This implementation uses separate kinetic and observation volumes for the complex. The main coefficient vector gives an untreated assay-signal baseline of approximately 0.034 pM. These are conditional source-vector calculations; original population observations are not reconstructed.","The main bootstrap-median vector and two printed SI starting/fixed vectors remain separate. Initial target is kin/kout. All context parameters except effective apparent clearance stay fixed.","The ADA configurations apply the reported fixed clearance shift once. Editing effective clearance is an exploratory coefficient change, not an ADA-status or population estimate.","Clearance bounds are authored 0.5–1.5× the extrema of the retained effective clearances. They are exploratory bounds, not confidence intervals or clinical limits.","Changing the simulation start uses the supplied initial state at that start and does not reconstruct earlier doses. The declared dose observation sides remain explicit.","No source figure panel, population fit, residual likelihood, repeated-dose prediction or original patient observations are reproduced. Fitting and normal server scans are unavailable."],"name":"Fixed 600 mg exposure","outputs":[{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"drug_serum","label":"Drug serum","unit":"nmol/L"},{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"target_free","label":"Target free","unit":"nmol/L"},{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"complex_serum","label":"Complex serum","unit":"nmol/L"},{"classification":"provisional","description":"Conditional concentration in nmol/L; source observation coordinates retained.","key":"assay_signal","label":"Assay signal","unit":"nmol/L"}],"scenario_id":"main_bootstrap_original_SI_600mg_ADA0","scientific_questions":["How do free cytokine and mixed assay signal respond to fixed subcutaneous exposure and clearance?"],"time_span":{"end":280,"start":0,"step":1}},{"controls":[{"category":"Antibody clearance","definition":"Effective CL/F after the selected fixed ADA context. 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The model has two biological states plus a separate clock.","The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.","Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.","Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"375 mg/m2 x2 weekly","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"standard_375mgm2_x2","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"No-dose equilibrium and execution marker; this control does not replay source tables or clinical outcomes.","interpretation_guardrails":["Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.","A1_mg is a latent rituximab effect amount, not a measured plasma concentration. 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They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Untreated equilibrium control","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"exact_source_table_anchor","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":0.001,"start":0,"step":0.001}},{"controls":[],"description":"Conditional deterministic K-PD calculation at fixed source estimates; no population intervals or individual relapse prediction.","interpretation_guardrails":["Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.","A1_mg is a latent rituximab effect amount, not a measured plasma concentration. The model has two biological states plus a separate clock.","The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.","Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.","Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"375 mg/m2 x4 weekly","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"standard_375mgm2_x4","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic K-PD calculation at fixed source estimates; no population intervals or individual relapse prediction.","interpretation_guardrails":["Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.","A1_mg is a latent rituximab effect amount, not a measured plasma concentration. The model has two biological states plus a separate clock.","The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.","Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.","Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"750 mg/m2 x2 weekly","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"standard_750mgm2_x2","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic K-PD calculation at fixed source estimates; no population intervals or individual relapse prediction.","interpretation_guardrails":["Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.","A1_mg is a latent rituximab effect amount, not a measured plasma concentration. The model has two biological states plus a separate clock.","The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.","Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.","Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"750 mg/m2 x1","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"standard_750mgm2_x1","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic K-PD calculation at fixed source estimates; no population intervals or individual relapse prediction.","interpretation_guardrails":["Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.","A1_mg is a latent rituximab effect amount, not a measured plasma concentration. The model has two biological states plus a separate clock.","The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.","Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.","Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"375 mg/m2 x1","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"standard_375mgm2_x1","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic K-PD calculation at fixed source estimates; no population intervals or individual relapse prediction.","interpretation_guardrails":["Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.","A1_mg is a latent rituximab effect amount, not a measured plasma concentration. The model has two biological states plus a separate clock.","The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.","Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.","Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"100 mg x1","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"single_100mg","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic K-PD calculation at fixed source estimates; no population intervals or individual relapse prediction.","interpretation_guardrails":["Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.","A1_mg is a latent rituximab effect amount, not a measured plasma concentration. The model has two biological states plus a separate clock.","The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.","Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.","Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Six monthly 100 mg","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"mini_six_monthly_100mg","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic K-PD calculation at fixed source estimates; no population intervals or individual relapse prediction.","interpretation_guardrails":["Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.","A1_mg is a latent rituximab effect amount, not a measured plasma concentration. The model has two biological states plus a separate clock.","The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.","Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.","Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Three 200 mg every 2 months","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"mini_three_200mg_q2mo","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic K-PD calculation at fixed source estimates; no population intervals or individual relapse prediction.","interpretation_guardrails":["Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.","A1_mg is a latent rituximab effect amount, not a measured plasma concentration. The model has two biological states plus a separate clock.","The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.","Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.","Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Three 150 mg every 2 months","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"mini_three_150mg_q2mo","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic K-PD calculation at fixed source estimates; no population intervals or individual relapse prediction.","interpretation_guardrails":["Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.","A1_mg is a latent rituximab effect amount, not a measured plasma concentration. The model has two biological states plus a separate clock.","The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.","Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.","Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Three 100 mg every 2 months","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"mini_three_100mg_q2mo","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[{"category":"baseline covariate","definition":"Baseline serum IgA modifies the latent effect amount needed for half-maximal B-cell depletion: effective ED50 scales as (IgA / 1.15 g/L)^1.39. Doses remain fixed when IgA changes.","description":"Baseline serum IgA modifies the latent effect amount needed for half-maximal B-cell depletion: effective ED50 scales as (IgA / 1.15 g/L)^1.39. Doses remain fixed when IgA changes.","key":"iga_g_l","label":"Baseline IgA","max":2.26,"min":0.11,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Li et al., DOI 10.3389/fphar.2024.1526936, final IgA covariate relationship and source sensitivity conditions. The 0.11–2.26 g/L domain is exploratory and is not a clinically validated range.","step":0.001,"unit":"g/L","value":0.11}],"description":"Conditional deterministic K-PD calculation at fixed source estimates; no population intervals or individual relapse prediction.","interpretation_guardrails":["Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.","A1_mg is a latent rituximab effect amount, not a measured plasma concentration. The model has two biological states plus a separate clock.","The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.","Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.","Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Two weekly 375 mg/m2 at low IgA","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"iga_min_two_weekly_375mgm2_x2","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[{"category":"baseline covariate","definition":"Baseline serum IgA modifies the latent effect amount needed for half-maximal B-cell depletion: effective ED50 scales as (IgA / 1.15 g/L)^1.39. Doses remain fixed when IgA changes.","description":"Baseline serum IgA modifies the latent effect amount needed for half-maximal B-cell depletion: effective ED50 scales as (IgA / 1.15 g/L)^1.39. Doses remain fixed when IgA changes.","key":"iga_g_l","label":"Baseline IgA","max":2.26,"min":0.11,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Li et al., DOI 10.3389/fphar.2024.1526936, final IgA covariate relationship and source sensitivity conditions. The 0.11–2.26 g/L domain is exploratory and is not a clinically validated range.","step":0.01,"unit":"g/L","value":1.15}],"description":"Conditional deterministic K-PD calculation at fixed source estimates; no population intervals or individual relapse prediction.","interpretation_guardrails":["Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.","A1_mg is a latent rituximab effect amount, not a measured plasma concentration. The model has two biological states plus a separate clock.","The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.","Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.","Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Two weekly 375 mg/m2 at median IgA","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"iga_median_two_weekly_375mgm2_x2","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[{"category":"baseline covariate","definition":"Baseline serum IgA modifies the latent effect amount needed for half-maximal B-cell depletion: effective ED50 scales as (IgA / 1.15 g/L)^1.39. Doses remain fixed when IgA changes.","description":"Baseline serum IgA modifies the latent effect amount needed for half-maximal B-cell depletion: effective ED50 scales as (IgA / 1.15 g/L)^1.39. Doses remain fixed when IgA changes.","key":"iga_g_l","label":"Baseline IgA","max":2.26,"min":0.11,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Li et al., DOI 10.3389/fphar.2024.1526936, final IgA covariate relationship and source sensitivity conditions. The 0.11–2.26 g/L domain is exploratory and is not a clinically validated range.","step":0.01,"unit":"g/L","value":2.26}],"description":"Conditional deterministic K-PD calculation at fixed source estimates; no population intervals or individual relapse prediction.","interpretation_guardrails":["Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.","A1_mg is a latent rituximab effect amount, not a measured plasma concentration. The model has two biological states plus a separate clock.","The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.","Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.","Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Two weekly 375 mg/m2 at high IgA","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"iga_max_two_weekly_375mgm2_x2","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Additional conditional calculation with a fixed regimen-specific ED50 multiplier. 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These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Exploratory ED50 condition: 375 mg/m2 x4 weekly","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"standard_375mgm2_x4_calibrated_endpoint_replay","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Additional conditional calculation with a fixed regimen-specific ED50 multiplier. 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These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Exploratory ED50 condition: 750 mg/m2 x2 weekly","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"standard_750mgm2_x2_calibrated_endpoint_replay","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Additional conditional calculation with a fixed regimen-specific ED50 multiplier. 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These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Exploratory ED50 condition: 375 mg/m2 x2 weekly","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"standard_375mgm2_x2_calibrated_endpoint_replay","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Additional conditional calculation with a fixed regimen-specific ED50 multiplier. Ordinary source-parameter conditions are retained separately.","interpretation_guardrails":["Conditional fixed-effect K-PD calculations; no original population fit, random effects, residual error, prediction intervals or complete paper reproduction.","A1_mg is a latent rituximab effect amount, not a measured plasma concentration. The model has two biological states plus a separate clock.","The observed clinical protocol was two weekly IV doses of 375 mg/m2, capped at 500 mg. Presets also include distinct theoretical simulation regimens, including 750 mg/m2; the clinical cap is not applied to those theoretical arms.","Preset doses are fixed absolute mg derived, where applicable, from BSA 0.82 m2. Editing IgA does not change doses; BSA is inspection-only. Instantaneous latent-amount additions approximate day-scale dosing; infusion durations were not reported.","Monthly and every-two-month schedules use 30-day and 60-day intervals. These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Exploratory ED50 condition: 750 mg/m2 x1","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"standard_750mgm2_x1_calibrated_endpoint_replay","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Additional conditional calculation with a fixed regimen-specific ED50 multiplier. 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These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Exploratory ED50 condition: 375 mg/m2 x1","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"standard_375mgm2_x1_calibrated_endpoint_replay","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Additional conditional calculation with a fixed regimen-specific ED50 multiplier. 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These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Exploratory ED50 condition: 100 mg x1","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"single_100mg_calibrated_endpoint_replay","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Additional conditional calculation with a fixed regimen-specific ED50 multiplier. 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These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Exploratory ED50 condition: Six monthly 100 mg","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"mini_six_monthly_100mg_calibrated_endpoint_replay","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Additional conditional calculation with a fixed regimen-specific ED50 multiplier. 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These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Exploratory ED50 condition: Three 200 mg every 2 months","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"mini_three_200mg_q2mo_calibrated_endpoint_replay","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Additional conditional calculation with a fixed regimen-specific ED50 multiplier. 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These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Exploratory ED50 condition: Three 150 mg every 2 months","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"mini_three_150mg_q2mo_calibrated_endpoint_replay","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}},{"controls":[],"description":"Additional conditional calculation with a fixed regimen-specific ED50 multiplier. 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These are conditional calendar approximations.","IgA is the only final fixed-effect covariate. The positive 0.11–2.26 g/L exploration domain comes from the source sensitivity conditions, not a clinically validated range.","Ten exploratory ED50 conditions retain a different fixed multiplier for each regimen. They are additional conditional calculations, not independent validation or population predictions.","B-cell repletion means the first upward crossing above 10 cells/uL after depletion, measured from first treatment. Instantaneous cell count or normalized recovery alone does not calculate that event time.","The separate clinical survival/nomogram analysis is not implemented. No individual relapse probability, concentration PK, clearance, volume or concentration AUC is returned.","Changing the simulation start applies the supplied initial state there; it does not reconstruct prior doses. Fitting and normal server parameter scans are unavailable."],"name":"Exploratory ED50 condition: Three 100 mg every 2 months","outputs":[{"classification":"provisional","description":"Absolute conditional CD19+ B-cell count.","key":"cd19_cells_ul","label":"CD19 b cell count","unit":"cells/uL"},{"classification":"provisional","description":"Count divided by Kin/Kout; one is the untreated model equilibrium.","key":"bcell_baseline_fraction","label":"B cell recovery relative to model baseline","unit":"dimensionless"},{"classification":"provisional","description":"Unmeasured K-PD effect coordinate; not plasma concentration.","key":"A1_mg","label":"Latent rituximab effect amount","unit":"mg"},{"classification":"provisional","description":"ED50 times the fixed exploratory multiplier and (IgA/1.15)^1.39.","key":"effective_ED50_mg","label":"Effective half maximal effect amount","unit":"mg"}],"scenario_id":"mini_three_100mg_q2mo_calibrated_endpoint_replay","scientific_questions":["How do the selected fixed regimen and positive IgA condition alter B-cell depletion and recovery?"],"time_span":{"end":365,"start":0,"step":1}}],"targets":[{"key":"cd20","label":"CD20 / MS4A1"}],"therapeutics":[{"key":"rituximab","label":"Rituximab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.1.0"},{"availability":{"catalog_qualified":true,"released":true},"description":"Mechanistic rat QSP coupling whole-body AAV biodistribution, intracellular transduction, transgene-derived anti-TargetX mAb, FcRn-aware protein PBPK, TargetX binding, and detailed brain/CSF transport across 725 explicit scalar states.","diseases":[{"key":"not_disease_specific_preclinical_cns_delivery","label":"Preclinical CNS antibody delivery (not disease-specific)","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s10928-026-10051-w","locator":"Primary publication title and abstract describe AAV-mediated antibody delivery in rat brain without a disease indication.","relationship":"Explicit non-disease-specific context; no disease indication is inferred."}}],"links":{"page":"/modeling/models/liu-2026-aav-mab-targetx-rat-brain-full-qsp","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"AAV-mediated monoclonal antibody gene delivery","model_classes":["PBPK","QSP","TMDD"],"model_id":"liu_2026_aav_mab_targetx_rat_brain_full_qsp","name":"Whole-body AAV–anti-TargetX rat brain QSP","outputs":[{"description":"Whole-blood vector-genome concentration for route and serotype biodistribution comparison.","key":"aav_blood_Vg_mL","label":"AAV in whole blood","unit":"Vg/mL"},{"description":"Volume-weighted vector-genome concentration across modeled brain vascular, barrier, CSF, meningeal, and cellular spaces.","key":"aav_brain_Vg_mL","label":"AAV in total brain","unit":"Vg/mL"},{"description":"Circulating transgene-derived or exogenously dosed antibody.","key":"mab_plasma_nM","label":"Anti target x m ab in plasma","unit":"nM"},{"description":"Volume-weighted modeled antibody across brain vascular, ISF, BBB, BCSFB, and parenchymal endosomal spaces.","key":"mab_brain_nM","label":"Anti target x m ab in total brain","unit":"nM"},{"description":"Free cisterna-magna TargetX normalized to its pre-dose model baseline; this is the Figure 7 CSF mapping.","key":"target_csf_pct_baseline","label":"Free target x in cisterna magna csf","unit":"% baseline"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[{"category":"published fixed","definition":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","description":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","key":"aav_kdeg_h","label":"AAV degradation rate","max":1.5105,"min":0.5035,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":0.01,"unit":"1/h","value":1.007},{"category":"published fixed","definition":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","description":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","key":"ps_mab_L_h","label":"Antibody permeability–surface area coefficient","max":3.93e-07,"min":1.31e-07,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":1e-09,"unit":"L/h","value":2.62e-07}],"description":"Unit-normalized six-hour exogenous TargetX bolus disposition. The source does not disclose the administered amount, so only the population-fit curve shape and reported 1.4 h half-life are compared.","interpretation_guardrails":["Research-only rat forward simulation; do not interpret as a dose recommendation, clinical prediction, or sponsor-fit replay.","Figures 3–6 comparisons use raster-derived sponsor population-fit curves and therefore establish diagnostic public-figure consistency rather than parity to unreleased source coordinates."],"name":"Exogenous TargetX disposition","outputs":[{"classification":"provisional","description":"Modeled free TargetX concentration in plasma.","key":"target_plasma_pM","label":"Free target x in plasma","unit":"pM"}],"scenario_id":"figure3a_exogenous_targetx_shape","scientific_questions":["Does exogenous plasma TargetX show the reported rapid disposition shape?"],"time_span":{"end":6,"start":0,"step":0.1}},{"controls":[{"category":"published fixed","definition":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","description":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","key":"aav_kdeg_h","label":"AAV degradation rate","max":1.5105,"min":0.5035,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":0.01,"unit":"1/h","value":1.007},{"category":"published fixed","definition":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","description":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","key":"ps_mab_L_h","label":"Antibody permeability–surface area coefficient","max":3.93e-07,"min":1.31e-07,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":1e-09,"unit":"L/h","value":2.62e-07}],"description":"Twenty-one-day no-dose TargetX equilibration for the disclosed plasma, brain-ISF, and lateral-ventricle CSF anchors.","interpretation_guardrails":["Research-only rat forward simulation; do not interpret as a dose recommendation, clinical prediction, or sponsor-fit replay.","Figures 3–6 comparisons use raster-derived sponsor population-fit curves and therefore establish diagnostic public-figure consistency rather than parity to unreleased source coordinates."],"name":"TargetX steady-state calibration","outputs":[{"classification":"qualified","description":"Modeled free TargetX concentration in plasma.","key":"target_plasma_pM","label":"Free target x in plasma","unit":"pM"},{"classification":"qualified","description":"Modeled free TargetX concentration in brain interstitial fluid.","key":"target_isf_pM","label":"Free target x in brain isf","unit":"pM"},{"classification":"qualified","description":"Modeled free TargetX concentration in ventricular cerebrospinal fluid.","key":"target_lv_pM","label":"Free target x in ventricular csf","unit":"pM"}],"scenario_id":"figure3b_targetx_steady_state","scientific_questions":["Do plasma, brain-ISF, and ventricular-CSF TargetX approach the disclosed baselines?"],"time_span":{"end":0,"start":-504,"step":6}},{"controls":[{"category":"published fixed","definition":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","description":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","key":"aav_kdeg_h","label":"AAV degradation rate","max":1.5105,"min":0.5035,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":0.01,"unit":"1/h","value":1.007},{"category":"published fixed","definition":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","description":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","key":"ps_mab_L_h","label":"Antibody permeability–surface area coefficient","max":3.93e-07,"min":1.31e-07,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":1e-09,"unit":"L/h","value":2.62e-07}],"description":"Figure 3C-F 3 mg/kg IV anti-TargetX mAb regimen. Dose amount assumes the disclosed 0.280 kg rat physiology and a 150 kDa IgG conversion; the source does not disclose individual animal weights or administration duration.","interpretation_guardrails":["Research-only rat forward simulation; do not interpret as a dose recommendation, clinical prediction, or sponsor-fit replay.","Figures 3–6 comparisons use raster-derived sponsor population-fit curves and therefore establish diagnostic public-figure consistency rather than parity to unreleased source coordinates."],"name":"IV anti-TargetX mAb — 3 mg/kg","outputs":[{"classification":"provisional","description":"Plasma concentration after an intravenous anti-TargetX mAb dose.","key":"mab_plasma_ug_mL","label":"Anti target x m ab in plasma","unit":"µg/mL"},{"classification":"provisional","description":"Brain interstitial-fluid concentration after an intravenous anti-TargetX mAb dose.","key":"mab_isf_ug_mL","label":"Anti target x m ab in brain isf","unit":"µg/mL"},{"classification":"provisional","description":"Cerebrospinal-fluid concentration after an intravenous anti-TargetX mAb dose.","key":"mab_csf_ug_mL","label":"Anti target x m ab in csf","unit":"µg/mL"},{"classification":"provisional","description":"Modeled free TargetX concentration in cerebrospinal fluid.","key":"target_csf_pM","label":"Free target x in csf","unit":"pM"}],"scenario_id":"figure3_mab_iv_3mgkg","scientific_questions":["How does an exogenous IV anti-TargetX mAb dose distribute between plasma, brain ISF, and CSF?"],"time_span":{"end":504,"start":-1000,"step":6}},{"controls":[{"category":"published fixed","definition":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","description":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","key":"aav_kdeg_h","label":"AAV degradation rate","max":1.5105,"min":0.5035,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":0.01,"unit":"1/h","value":1.007},{"category":"published fixed","definition":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","description":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","key":"ps_mab_L_h","label":"Antibody permeability–surface area coefficient","max":3.93e-07,"min":1.31e-07,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":1e-09,"unit":"L/h","value":2.62e-07}],"description":"Figure 3C-F 10 mg/kg IV anti-TargetX mAb regimen. Dose amount assumes the disclosed 0.280 kg rat physiology and a 150 kDa IgG conversion; the source does not disclose individual animal weights or administration duration.","interpretation_guardrails":["Research-only rat forward simulation; do not interpret as a dose recommendation, clinical prediction, or sponsor-fit replay.","Figures 3–6 comparisons use raster-derived sponsor population-fit curves and therefore establish diagnostic public-figure consistency rather than parity to unreleased source coordinates."],"name":"IV anti-TargetX mAb — 10 mg/kg","outputs":[{"classification":"provisional","description":"Plasma concentration after an intravenous anti-TargetX mAb dose.","key":"mab_plasma_ug_mL","label":"Anti target x m ab in plasma","unit":"µg/mL"},{"classification":"provisional","description":"Brain interstitial-fluid concentration after an intravenous anti-TargetX mAb dose.","key":"mab_isf_ug_mL","label":"Anti target x m ab in brain isf","unit":"µg/mL"},{"classification":"provisional","description":"Cerebrospinal-fluid concentration after an intravenous anti-TargetX mAb dose.","key":"mab_csf_ug_mL","label":"Anti target x m ab in csf","unit":"µg/mL"},{"classification":"provisional","description":"Modeled free TargetX concentration in cerebrospinal fluid.","key":"target_csf_pM","label":"Free target x in csf","unit":"pM"}],"scenario_id":"figure3_mab_iv_10mgkg","scientific_questions":["How does an exogenous IV anti-TargetX mAb dose distribute between plasma, brain ISF, and CSF?"],"time_span":{"end":504,"start":-1000,"step":6}},{"controls":[{"category":"published fixed","definition":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","description":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","key":"aav_kdeg_h","label":"AAV degradation rate","max":1.5105,"min":0.5035,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":0.01,"unit":"1/h","value":1.007},{"category":"published fixed","definition":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","description":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","key":"ps_mab_L_h","label":"Antibody permeability–surface area coefficient","max":3.93e-07,"min":1.31e-07,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":1e-09,"unit":"L/h","value":2.62e-07}],"description":"Figure 3C-F 30 mg/kg IV anti-TargetX mAb regimen. Dose amount assumes the disclosed 0.280 kg rat physiology and a 150 kDa IgG conversion; the source does not disclose individual animal weights or administration duration.","interpretation_guardrails":["Research-only rat forward simulation; do not interpret as a dose recommendation, clinical prediction, or sponsor-fit replay.","Figures 3–6 comparisons use raster-derived sponsor population-fit curves and therefore establish diagnostic public-figure consistency rather than parity to unreleased source coordinates."],"name":"IV anti-TargetX mAb — 30 mg/kg","outputs":[{"classification":"provisional","description":"Plasma concentration after an intravenous anti-TargetX mAb dose.","key":"mab_plasma_ug_mL","label":"Anti target x m ab in plasma","unit":"µg/mL"},{"classification":"provisional","description":"Brain interstitial-fluid concentration after an intravenous anti-TargetX mAb dose.","key":"mab_isf_ug_mL","label":"Anti target x m ab in brain isf","unit":"µg/mL"},{"classification":"provisional","description":"Cerebrospinal-fluid concentration after an intravenous anti-TargetX mAb dose.","key":"mab_csf_ug_mL","label":"Anti target x m ab in csf","unit":"µg/mL"},{"classification":"provisional","description":"Modeled free TargetX concentration in cerebrospinal fluid.","key":"target_csf_pM","label":"Free target x in csf","unit":"pM"}],"scenario_id":"figure3_mab_iv_30mgkg","scientific_questions":["How does an exogenous IV anti-TargetX mAb dose distribute between plasma, brain ISF, and CSF?"],"time_span":{"end":504,"start":-1000,"step":6}},{"controls":[{"category":"published fixed","definition":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","description":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","key":"aav_kdeg_h","label":"AAV degradation rate","max":1.5105,"min":0.5035,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":0.01,"unit":"1/h","value":1.007},{"category":"published fixed","definition":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","description":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","key":"ps_mab_L_h","label":"Antibody permeability–surface area coefficient","max":3.93e-07,"min":1.31e-07,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":1e-09,"unit":"L/h","value":2.62e-07}],"description":"Figure 3C-F 100 mg/kg IV anti-TargetX mAb regimen. Dose amount assumes the disclosed 0.280 kg rat physiology and a 150 kDa IgG conversion; the source does not disclose individual animal weights or administration duration.","interpretation_guardrails":["Research-only rat forward simulation; do not interpret as a dose recommendation, clinical prediction, or sponsor-fit replay.","Figures 3–6 comparisons use raster-derived sponsor population-fit curves and therefore establish diagnostic public-figure consistency rather than parity to unreleased source coordinates."],"name":"IV anti-TargetX mAb — 100 mg/kg","outputs":[{"classification":"provisional","description":"Plasma concentration after an intravenous anti-TargetX mAb dose.","key":"mab_plasma_ug_mL","label":"Anti target x m ab in plasma","unit":"µg/mL"},{"classification":"provisional","description":"Brain interstitial-fluid concentration after an intravenous anti-TargetX mAb dose.","key":"mab_isf_ug_mL","label":"Anti target x m ab in brain isf","unit":"µg/mL"},{"classification":"provisional","description":"Cerebrospinal-fluid concentration after an intravenous anti-TargetX mAb dose.","key":"mab_csf_ug_mL","label":"Anti target x m ab in csf","unit":"µg/mL"},{"classification":"provisional","description":"Modeled free TargetX concentration in cerebrospinal fluid.","key":"target_csf_pM","label":"Free target x in csf","unit":"pM"}],"scenario_id":"figure3_mab_iv_100mgkg","scientific_questions":["How does an exogenous IV anti-TargetX mAb dose distribute between plasma, brain ISF, and CSF?"],"time_span":{"end":504,"start":-1000,"step":6}},{"controls":[{"category":"published fixed","definition":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","description":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","key":"aav_kdeg_h","label":"AAV degradation rate","max":1.5105,"min":0.5035,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":0.01,"unit":"1/h","value":1.007},{"category":"published fixed","definition":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","description":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","key":"ps_mab_L_h","label":"Antibody permeability–surface area coefficient","max":3.93e-07,"min":1.31e-07,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":1e-09,"unit":"L/h","value":2.62e-07}],"description":"Systemic AAV9 delivery after 1000 h receptor and TargetX pre-equilibration.","interpretation_guardrails":["Research-only rat forward simulation; do not interpret as a dose recommendation, clinical prediction, or sponsor-fit replay.","Figures 3–6 comparisons use raster-derived sponsor population-fit curves and therefore establish diagnostic public-figure consistency rather than parity to unreleased source coordinates."],"name":"Systemic AAV9 delivery — 5E12 Vg IV","outputs":[{"classification":"provisional","description":"Whole-blood vector-genome concentration for route and serotype biodistribution comparison.","key":"aav_blood_Vg_mL","label":"AAV in whole blood","unit":"Vg/mL"},{"classification":"provisional","description":"Volume-weighted vector-genome concentration across modeled brain vascular, barrier, CSF, meningeal, and cellular spaces.","key":"aav_brain_Vg_mL","label":"AAV in total brain","unit":"Vg/mL"},{"classification":"provisional","description":"Circulating transgene-derived or exogenously dosed antibody.","key":"mab_plasma_nM","label":"Anti target x m ab in plasma","unit":"nM"},{"classification":"provisional","description":"Volume-weighted modeled antibody across brain vascular, ISF, BBB, BCSFB, and parenchymal endosomal spaces.","key":"mab_brain_nM","label":"Anti target x m ab in total brain","unit":"nM"},{"classification":"qualified","description":"Free cisterna-magna TargetX normalized to its pre-dose model baseline; this is the Figure 7 CSF mapping.","key":"target_csf_pct_baseline","label":"Free target x in cisterna magna csf","unit":"% baseline"}],"scenario_id":"iv_5e12_aav9","scientific_questions":["How do route, dose, and serotype shape vector biodistribution, antibody exposure, and free TargetX?"],"time_span":{"end":1344,"start":-1000,"step":24}},{"controls":[{"category":"published fixed","definition":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","description":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","key":"aav_kdeg_h","label":"AAV degradation rate","max":1.5105,"min":0.5035,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":0.01,"unit":"1/h","value":1.007},{"category":"published fixed","definition":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","description":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","key":"ps_mab_L_h","label":"Antibody permeability–surface area coefficient","max":3.93e-07,"min":1.31e-07,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":1e-09,"unit":"L/h","value":2.62e-07}],"description":"Low-dose AAV9 delivery into cisterna-magna CSF.","interpretation_guardrails":["Research-only rat forward simulation; do not interpret as a dose recommendation, clinical prediction, or sponsor-fit replay.","Figures 3–6 comparisons use raster-derived sponsor population-fit curves and therefore establish diagnostic public-figure consistency rather than parity to unreleased source coordinates."],"name":"Low-dose AAV9 delivery — 5E11 Vg ICM","outputs":[{"classification":"provisional","description":"Whole-blood vector-genome concentration for route and serotype biodistribution comparison.","key":"aav_blood_Vg_mL","label":"AAV in whole blood","unit":"Vg/mL"},{"classification":"provisional","description":"Volume-weighted vector-genome concentration across modeled brain vascular, barrier, CSF, meningeal, and cellular spaces.","key":"aav_brain_Vg_mL","label":"AAV in total brain","unit":"Vg/mL"},{"classification":"provisional","description":"Circulating transgene-derived or exogenously dosed antibody.","key":"mab_plasma_nM","label":"Anti target x m ab in plasma","unit":"nM"},{"classification":"provisional","description":"Volume-weighted modeled antibody across brain vascular, ISF, BBB, BCSFB, and parenchymal endosomal spaces.","key":"mab_brain_nM","label":"Anti target x m ab in total brain","unit":"nM"},{"classification":"qualified","description":"Free cisterna-magna TargetX normalized to its pre-dose model baseline; this is the Figure 7 CSF mapping.","key":"target_csf_pct_baseline","label":"Free target x in cisterna magna csf","unit":"% baseline"}],"scenario_id":"icm_5e11_aav9","scientific_questions":["How do route, dose, and serotype shape vector biodistribution, antibody exposure, and free TargetX?"],"time_span":{"end":1344,"start":-1000,"step":24}},{"controls":[{"category":"published fixed","definition":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","description":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","key":"aav_kdeg_h","label":"AAV degradation rate","max":1.5105,"min":0.5035,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":0.01,"unit":"1/h","value":1.007},{"category":"published fixed","definition":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","description":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","key":"ps_mab_L_h","label":"Antibody permeability–surface area coefficient","max":3.93e-07,"min":1.31e-07,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":1e-09,"unit":"L/h","value":2.62e-07}],"description":"Mid-dose AAV9 delivery into cisterna-magna CSF.","interpretation_guardrails":["Research-only rat forward simulation; do not interpret as a dose recommendation, clinical prediction, or sponsor-fit replay.","Figures 3–6 comparisons use raster-derived sponsor population-fit curves and therefore establish diagnostic public-figure consistency rather than parity to unreleased source coordinates."],"name":"Mid-dose AAV9 delivery — 1E12 Vg ICM","outputs":[{"classification":"provisional","description":"Whole-blood vector-genome concentration for route and serotype biodistribution comparison.","key":"aav_blood_Vg_mL","label":"AAV in whole blood","unit":"Vg/mL"},{"classification":"provisional","description":"Volume-weighted vector-genome concentration across modeled brain vascular, barrier, CSF, meningeal, and cellular spaces.","key":"aav_brain_Vg_mL","label":"AAV in total brain","unit":"Vg/mL"},{"classification":"provisional","description":"Circulating transgene-derived or exogenously dosed antibody.","key":"mab_plasma_nM","label":"Anti target x m ab in plasma","unit":"nM"},{"classification":"provisional","description":"Volume-weighted modeled antibody across brain vascular, ISF, BBB, BCSFB, and parenchymal endosomal spaces.","key":"mab_brain_nM","label":"Anti target x m ab in total brain","unit":"nM"},{"classification":"qualified","description":"Free cisterna-magna TargetX normalized to its pre-dose model baseline; this is the Figure 7 CSF mapping.","key":"target_csf_pct_baseline","label":"Free target x in cisterna magna csf","unit":"% baseline"}],"scenario_id":"icm_1e12_aav9","scientific_questions":["How do route, dose, and serotype shape vector biodistribution, antibody exposure, and free TargetX?"],"time_span":{"end":1344,"start":-1000,"step":24}},{"controls":[{"category":"published fixed","definition":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","description":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","key":"aav_kdeg_h","label":"AAV degradation rate","max":1.5105,"min":0.5035,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":0.01,"unit":"1/h","value":1.007},{"category":"published fixed","definition":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","description":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","key":"ps_mab_L_h","label":"Antibody permeability–surface area coefficient","max":3.93e-07,"min":1.31e-07,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":1e-09,"unit":"L/h","value":2.62e-07}],"description":"High-dose AAV9 delivery into cisterna-magna CSF.","interpretation_guardrails":["Research-only rat forward simulation; do not interpret as a dose recommendation, clinical prediction, or sponsor-fit replay.","Figures 3–6 comparisons use raster-derived sponsor population-fit curves and therefore establish diagnostic public-figure consistency rather than parity to unreleased source coordinates."],"name":"High-dose AAV9 delivery — 5E12 Vg ICM","outputs":[{"classification":"provisional","description":"Whole-blood vector-genome concentration for route and serotype biodistribution comparison.","key":"aav_blood_Vg_mL","label":"AAV in whole blood","unit":"Vg/mL"},{"classification":"provisional","description":"Volume-weighted vector-genome concentration across modeled brain vascular, barrier, CSF, meningeal, and cellular spaces.","key":"aav_brain_Vg_mL","label":"AAV in total brain","unit":"Vg/mL"},{"classification":"provisional","description":"Circulating transgene-derived or exogenously dosed antibody.","key":"mab_plasma_nM","label":"Anti target x m ab in plasma","unit":"nM"},{"classification":"provisional","description":"Volume-weighted modeled antibody across brain vascular, ISF, BBB, BCSFB, and parenchymal endosomal spaces.","key":"mab_brain_nM","label":"Anti target x m ab in total brain","unit":"nM"},{"classification":"qualified","description":"Free cisterna-magna TargetX normalized to its pre-dose model baseline; this is the Figure 7 CSF mapping.","key":"target_csf_pct_baseline","label":"Free target x in cisterna magna csf","unit":"% baseline"}],"scenario_id":"icm_5e12_aav9","scientific_questions":["How do route, dose, and serotype shape vector biodistribution, antibody exposure, and free TargetX?"],"time_span":{"end":1344,"start":-1000,"step":24}},{"controls":[{"category":"published fixed","definition":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","description":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","key":"aav_kdeg_h","label":"AAV degradation rate","max":1.5105,"min":0.5035,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":0.01,"unit":"1/h","value":1.007},{"category":"published fixed","definition":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","description":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","key":"ps_mab_L_h","label":"Antibody permeability–surface area coefficient","max":3.93e-07,"min":1.31e-07,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":1e-09,"unit":"L/h","value":2.62e-07}],"description":"Local AAV9 delivery into brain interstitial fluid.","interpretation_guardrails":["Research-only rat forward simulation; do not interpret as a dose recommendation, clinical prediction, or sponsor-fit replay.","Figures 3–6 comparisons use raster-derived sponsor population-fit curves and therefore establish diagnostic public-figure consistency rather than parity to unreleased source coordinates."],"name":"Local AAV9 delivery — 2.5E11 Vg IST","outputs":[{"classification":"provisional","description":"Whole-blood vector-genome concentration for route and serotype biodistribution comparison.","key":"aav_blood_Vg_mL","label":"AAV in whole blood","unit":"Vg/mL"},{"classification":"provisional","description":"Volume-weighted vector-genome concentration across modeled brain vascular, barrier, CSF, meningeal, and cellular spaces.","key":"aav_brain_Vg_mL","label":"AAV in total brain","unit":"Vg/mL"},{"classification":"provisional","description":"Circulating transgene-derived or exogenously dosed antibody.","key":"mab_plasma_nM","label":"Anti target x m ab in plasma","unit":"nM"},{"classification":"provisional","description":"Volume-weighted modeled antibody across brain vascular, ISF, BBB, BCSFB, and parenchymal endosomal spaces.","key":"mab_brain_nM","label":"Anti target x m ab in total brain","unit":"nM"},{"classification":"qualified","description":"Free cisterna-magna TargetX normalized to its pre-dose model baseline; this is the Figure 7 CSF mapping.","key":"target_csf_pct_baseline","label":"Free target x in cisterna magna csf","unit":"% baseline"}],"scenario_id":"ist_2_5e11_aav9","scientific_questions":["How do route, dose, and serotype shape vector biodistribution, antibody exposure, and free TargetX?"],"time_span":{"end":1344,"start":-1000,"step":24}},{"controls":[{"category":"published fixed","definition":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","description":"AAV degradation rate governing loss, degradation, or removal in the modeled biological process.","key":"aav_kdeg_h","label":"AAV degradation rate","max":7.5,"min":2.5,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":0.01,"unit":"1/h","value":5},{"category":"published fixed","definition":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","description":"Antibody permeability–surface area coefficient coefficient used by the released system of model equations.","key":"ps_mab_L_h","label":"Antibody permeability–surface area coefficient","max":3.93e-07,"min":1.31e-07,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Liu 2026 Table 1","step":1e-09,"unit":"L/h","value":2.62e-07}],"description":"AAV5 serotype comparison using the disclosed parameter overrides.","interpretation_guardrails":["Research-only rat forward simulation; do not interpret as a dose recommendation, clinical prediction, or sponsor-fit replay.","Figures 3–6 comparisons use raster-derived sponsor population-fit curves and therefore establish diagnostic public-figure consistency rather than parity to unreleased source coordinates."],"name":"AAV5 serotype comparison — 5E12 Vg ICM","outputs":[{"classification":"provisional","description":"Whole-blood vector-genome concentration for route and serotype biodistribution comparison.","key":"aav_blood_Vg_mL","label":"AAV in whole blood","unit":"Vg/mL"},{"classification":"provisional","description":"Volume-weighted vector-genome concentration across modeled brain vascular, barrier, CSF, meningeal, and cellular spaces.","key":"aav_brain_Vg_mL","label":"AAV in total brain","unit":"Vg/mL"},{"classification":"provisional","description":"Circulating transgene-derived or exogenously dosed antibody.","key":"mab_plasma_nM","label":"Anti target x m ab in plasma","unit":"nM"},{"classification":"provisional","description":"Volume-weighted modeled antibody across brain vascular, ISF, BBB, BCSFB, and parenchymal endosomal spaces.","key":"mab_brain_nM","label":"Anti target x m ab in total brain","unit":"nM"},{"classification":"qualified","description":"Free cisterna-magna TargetX normalized to its pre-dose model baseline; this is the Figure 7 CSF mapping.","key":"target_csf_pct_baseline","label":"Free target x in cisterna magna csf","unit":"% baseline"}],"scenario_id":"icm_5e12_aav5","scientific_questions":["How do route, dose, and serotype shape vector biodistribution, antibody exposure, and free TargetX?"],"time_span":{"end":1344,"start":-1000,"step":24}}],"targets":[{"key":"targetx_anonymized_paper_target","label":"TargetX (anonymized paper target)"}],"therapeutics":[{"key":"aav9_aav5_encoded_anti_targetx_monoclonal_antibody","label":"AAV9/AAV5-encoded anti-TargetX monoclonal antibody"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.1.7"},{"availability":{"catalog_qualified":true,"released":true},"description":"Explore local antibody expression, reversible target binding and turnover in three independent concentration systems.","diseases":[{"key":"exploratory_soluble_targetx_binding_and_antibody_expression","label":"Exploratory soluble TargetX binding and antibody expression"}],"links":{"page":"/modeling/models/liu-2026-aav-mab-targetx-rat-brain-reduced-qsp","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":null,"model_classes":["conditional reduced QSP","antibody–soluble-target binding"],"model_id":"liu_2026_aav_mab_targetx_rat_brain_reduced_qsp","name":"Rat-brain antibody and target response — reduced companion","outputs":[{"description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_plasma_nM","label":"Mab plasma","unit":"nM"},{"description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_isf_nM","label":"Mab isf","unit":"nM"},{"description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"target_isf_pct_baseline","label":"Target isf pct baseline","unit":"dimensionless"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Specified fixed initial drivers, local protein/target concentrations and hour calendar; no administered dose events.","interpretation_guardrails":["Three independent local concentration systems represent plasma, brain interstitial fluid and CSF. There are no inter-space flows or compartment volumes.","Transient, durable and lagged expression drivers are dimensionless authored inputs; they are not measured vector copies, administered vector doses or observed nuclear DNA.","Profile route, dose and serotype labels identify fixed authored initial-condition sets. No administration, dose-to-transduction or vector transport law is represented.","Production scales, effective loss rates and initial drivers are authored conditional inputs; original profile fitting is outside this scope.","Human binding affinity is assumed for rat. Target baselines are primary-model equilibrium predictions used as specified setpoints, not independent measured concentrations.","A common effective target-turnover closure and a single-stage expression lag are declared assumptions.","Each complex contains one antibody and one target. Accounting remains a local concentration balance; no cross-space mass or volume-weighted conservation is asserted.","Forty read-only primary reference facts provide context and do not enter the companion equations or represent additional simulated observations.","No whole-primary-model, published-figure, sampled-population, clinical translation, immunogenicity or gene-delivery optimization result is assigned."],"name":"IST 2.5E11 Vg AAV9 — fixed expression profile","outputs":[{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_plasma_nM","label":"Mab plasma","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_isf_nM","label":"Mab isf","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"target_isf_pct_baseline","label":"Target isf pct baseline","unit":"dimensionless"}],"scenario_id":"ist-2-5e11-aav9","scientific_questions":["How do the model's key biological readouts change under ist 2.5e11 vg aav9 — fixed expression profile?"],"time_span":{"end":1344,"start":0,"step":12}},{"controls":[],"description":"Specified fixed initial drivers, local protein/target concentrations and hour calendar; no administered dose events.","interpretation_guardrails":["Three independent local concentration systems represent plasma, brain interstitial fluid and CSF. There are no inter-space flows or compartment volumes.","Transient, durable and lagged expression drivers are dimensionless authored inputs; they are not measured vector copies, administered vector doses or observed nuclear DNA.","Profile route, dose and serotype labels identify fixed authored initial-condition sets. No administration, dose-to-transduction or vector transport law is represented.","Production scales, effective loss rates and initial drivers are authored conditional inputs; original profile fitting is outside this scope.","Human binding affinity is assumed for rat. Target baselines are primary-model equilibrium predictions used as specified setpoints, not independent measured concentrations.","A common effective target-turnover closure and a single-stage expression lag are declared assumptions.","Each complex contains one antibody and one target. Accounting remains a local concentration balance; no cross-space mass or volume-weighted conservation is asserted.","Forty read-only primary reference facts provide context and do not enter the companion equations or represent additional simulated observations.","No whole-primary-model, published-figure, sampled-population, clinical translation, immunogenicity or gene-delivery optimization result is assigned."],"name":"ICM 5E11 Vg AAV9 — fixed expression profile","outputs":[{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_plasma_nM","label":"Mab plasma","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_isf_nM","label":"Mab isf","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"target_isf_pct_baseline","label":"Target isf pct baseline","unit":"dimensionless"}],"scenario_id":"icm-5e11-aav9","scientific_questions":["How do the model's key biological readouts change under icm 5e11 vg aav9 — fixed expression profile?"],"time_span":{"end":1344,"start":0,"step":12}},{"controls":[],"description":"Specified fixed initial drivers, local protein/target concentrations and hour calendar; no administered dose events.","interpretation_guardrails":["Three independent local concentration systems represent plasma, brain interstitial fluid and CSF. There are no inter-space flows or compartment volumes.","Transient, durable and lagged expression drivers are dimensionless authored inputs; they are not measured vector copies, administered vector doses or observed nuclear DNA.","Profile route, dose and serotype labels identify fixed authored initial-condition sets. No administration, dose-to-transduction or vector transport law is represented.","Production scales, effective loss rates and initial drivers are authored conditional inputs; original profile fitting is outside this scope.","Human binding affinity is assumed for rat. Target baselines are primary-model equilibrium predictions used as specified setpoints, not independent measured concentrations.","A common effective target-turnover closure and a single-stage expression lag are declared assumptions.","Each complex contains one antibody and one target. Accounting remains a local concentration balance; no cross-space mass or volume-weighted conservation is asserted.","Forty read-only primary reference facts provide context and do not enter the companion equations or represent additional simulated observations.","No whole-primary-model, published-figure, sampled-population, clinical translation, immunogenicity or gene-delivery optimization result is assigned."],"name":"ICM 1E12 Vg AAV9 — fixed expression profile","outputs":[{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_plasma_nM","label":"Mab plasma","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_isf_nM","label":"Mab isf","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"target_isf_pct_baseline","label":"Target isf pct baseline","unit":"dimensionless"}],"scenario_id":"icm-1e12-aav9","scientific_questions":["How do the model's key biological readouts change under icm 1e12 vg aav9 — fixed expression profile?"],"time_span":{"end":1344,"start":0,"step":12}},{"controls":[],"description":"Specified fixed initial drivers, local protein/target concentrations and hour calendar; no administered dose events.","interpretation_guardrails":["Three independent local concentration systems represent plasma, brain interstitial fluid and CSF. There are no inter-space flows or compartment volumes.","Transient, durable and lagged expression drivers are dimensionless authored inputs; they are not measured vector copies, administered vector doses or observed nuclear DNA.","Profile route, dose and serotype labels identify fixed authored initial-condition sets. No administration, dose-to-transduction or vector transport law is represented.","Production scales, effective loss rates and initial drivers are authored conditional inputs; original profile fitting is outside this scope.","Human binding affinity is assumed for rat. Target baselines are primary-model equilibrium predictions used as specified setpoints, not independent measured concentrations.","A common effective target-turnover closure and a single-stage expression lag are declared assumptions.","Each complex contains one antibody and one target. Accounting remains a local concentration balance; no cross-space mass or volume-weighted conservation is asserted.","Forty read-only primary reference facts provide context and do not enter the companion equations or represent additional simulated observations.","No whole-primary-model, published-figure, sampled-population, clinical translation, immunogenicity or gene-delivery optimization result is assigned."],"name":"ICM 5E12 Vg AAV9 — fixed expression profile","outputs":[{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_plasma_nM","label":"Mab plasma","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_isf_nM","label":"Mab isf","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"target_isf_pct_baseline","label":"Target isf pct baseline","unit":"dimensionless"}],"scenario_id":"icm-5e12-aav9","scientific_questions":["How do the model's key biological readouts change under icm 5e12 vg aav9 — fixed expression profile?"],"time_span":{"end":1344,"start":0,"step":12}},{"controls":[],"description":"Specified fixed initial drivers, local protein/target concentrations and hour calendar; no administered dose events.","interpretation_guardrails":["Three independent local concentration systems represent plasma, brain interstitial fluid and CSF. There are no inter-space flows or compartment volumes.","Transient, durable and lagged expression drivers are dimensionless authored inputs; they are not measured vector copies, administered vector doses or observed nuclear DNA.","Profile route, dose and serotype labels identify fixed authored initial-condition sets. No administration, dose-to-transduction or vector transport law is represented.","Production scales, effective loss rates and initial drivers are authored conditional inputs; original profile fitting is outside this scope.","Human binding affinity is assumed for rat. Target baselines are primary-model equilibrium predictions used as specified setpoints, not independent measured concentrations.","A common effective target-turnover closure and a single-stage expression lag are declared assumptions.","Each complex contains one antibody and one target. Accounting remains a local concentration balance; no cross-space mass or volume-weighted conservation is asserted.","Forty read-only primary reference facts provide context and do not enter the companion equations or represent additional simulated observations.","No whole-primary-model, published-figure, sampled-population, clinical translation, immunogenicity or gene-delivery optimization result is assigned."],"name":"ICM 5E12 Vg AAV5 — fixed expression profile","outputs":[{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_plasma_nM","label":"Mab plasma","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_isf_nM","label":"Mab isf","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"target_isf_pct_baseline","label":"Target isf pct baseline","unit":"dimensionless"}],"scenario_id":"icm-5e12-aav5","scientific_questions":["How do the model's key biological readouts change under icm 5e12 vg aav5 — fixed expression profile?"],"time_span":{"end":1344,"start":0,"step":12}},{"controls":[],"description":"Specified fixed initial drivers, local protein/target concentrations and hour calendar; no administered dose events.","interpretation_guardrails":["Three independent local concentration systems represent plasma, brain interstitial fluid and CSF. There are no inter-space flows or compartment volumes.","Transient, durable and lagged expression drivers are dimensionless authored inputs; they are not measured vector copies, administered vector doses or observed nuclear DNA.","Profile route, dose and serotype labels identify fixed authored initial-condition sets. No administration, dose-to-transduction or vector transport law is represented.","Production scales, effective loss rates and initial drivers are authored conditional inputs; original profile fitting is outside this scope.","Human binding affinity is assumed for rat. Target baselines are primary-model equilibrium predictions used as specified setpoints, not independent measured concentrations.","A common effective target-turnover closure and a single-stage expression lag are declared assumptions.","Each complex contains one antibody and one target. Accounting remains a local concentration balance; no cross-space mass or volume-weighted conservation is asserted.","Forty read-only primary reference facts provide context and do not enter the companion equations or represent additional simulated observations.","No whole-primary-model, published-figure, sampled-population, clinical translation, immunogenicity or gene-delivery optimization result is assigned."],"name":"IV 5E12 Vg AAV9 — fixed expression profile","outputs":[{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_plasma_nM","label":"Mab plasma","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_isf_nM","label":"Mab isf","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"target_isf_pct_baseline","label":"Target isf pct baseline","unit":"dimensionless"}],"scenario_id":"iv-5e12-aav9","scientific_questions":["How do the model's key biological readouts change under iv 5e12 vg aav9 — fixed expression profile?"],"time_span":{"end":1344,"start":0,"step":12}},{"controls":[],"description":"Specified fixed initial drivers, local protein/target concentrations and hour calendar; no administered dose events.","interpretation_guardrails":["Three independent local concentration systems represent plasma, brain interstitial fluid and CSF. There are no inter-space flows or compartment volumes.","Transient, durable and lagged expression drivers are dimensionless authored inputs; they are not measured vector copies, administered vector doses or observed nuclear DNA.","Profile route, dose and serotype labels identify fixed authored initial-condition sets. No administration, dose-to-transduction or vector transport law is represented.","Production scales, effective loss rates and initial drivers are authored conditional inputs; original profile fitting is outside this scope.","Human binding affinity is assumed for rat. Target baselines are primary-model equilibrium predictions used as specified setpoints, not independent measured concentrations.","A common effective target-turnover closure and a single-stage expression lag are declared assumptions.","Each complex contains one antibody and one target. Accounting remains a local concentration balance; no cross-space mass or volume-weighted conservation is asserted.","Forty read-only primary reference facts provide context and do not enter the companion equations or represent additional simulated observations.","No whole-primary-model, published-figure, sampled-population, clinical translation, immunogenicity or gene-delivery optimization result is assigned."],"name":"Local target baselines — no expression driver","outputs":[{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_plasma_nM","label":"Mab plasma","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_isf_nM","label":"Mab isf","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"target_isf_pct_baseline","label":"Target isf pct baseline","unit":"dimensionless"}],"scenario_id":"untreated-local-target-baselines","scientific_questions":["How do the model's key biological readouts change under local target baselines — no expression driver?"],"time_span":{"end":1344,"start":0,"step":12}},{"controls":[],"description":"Specified fixed initial drivers, local protein/target concentrations and hour calendar; no administered dose events.","interpretation_guardrails":["Three independent local concentration systems represent plasma, brain interstitial fluid and CSF. There are no inter-space flows or compartment volumes.","Transient, durable and lagged expression drivers are dimensionless authored inputs; they are not measured vector copies, administered vector doses or observed nuclear DNA.","Profile route, dose and serotype labels identify fixed authored initial-condition sets. No administration, dose-to-transduction or vector transport law is represented.","Production scales, effective loss rates and initial drivers are authored conditional inputs; original profile fitting is outside this scope.","Human binding affinity is assumed for rat. Target baselines are primary-model equilibrium predictions used as specified setpoints, not independent measured concentrations.","A common effective target-turnover closure and a single-stage expression lag are declared assumptions.","Each complex contains one antibody and one target. Accounting remains a local concentration balance; no cross-space mass or volume-weighted conservation is asserted.","Forty read-only primary reference facts provide context and do not enter the companion equations or represent additional simulated observations.","No whole-primary-model, published-figure, sampled-population, clinical translation, immunogenicity or gene-delivery optimization result is assigned."],"name":"Transient driver only — plasma","outputs":[{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_plasma_nM","label":"Mab plasma","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_isf_nM","label":"Mab isf","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"target_isf_pct_baseline","label":"Target isf pct baseline","unit":"dimensionless"}],"scenario_id":"transient-driver-only-plasma","scientific_questions":["How do the model's key biological readouts change under transient driver only — plasma?"],"time_span":{"end":1344,"start":0,"step":12}},{"controls":[],"description":"Specified fixed initial drivers, local protein/target concentrations and hour calendar; no administered dose events.","interpretation_guardrails":["Three independent local concentration systems represent plasma, brain interstitial fluid and CSF. There are no inter-space flows or compartment volumes.","Transient, durable and lagged expression drivers are dimensionless authored inputs; they are not measured vector copies, administered vector doses or observed nuclear DNA.","Profile route, dose and serotype labels identify fixed authored initial-condition sets. No administration, dose-to-transduction or vector transport law is represented.","Production scales, effective loss rates and initial drivers are authored conditional inputs; original profile fitting is outside this scope.","Human binding affinity is assumed for rat. Target baselines are primary-model equilibrium predictions used as specified setpoints, not independent measured concentrations.","A common effective target-turnover closure and a single-stage expression lag are declared assumptions.","Each complex contains one antibody and one target. Accounting remains a local concentration balance; no cross-space mass or volume-weighted conservation is asserted.","Forty read-only primary reference facts provide context and do not enter the companion equations or represent additional simulated observations.","No whole-primary-model, published-figure, sampled-population, clinical translation, immunogenicity or gene-delivery optimization result is assigned."],"name":"Transient driver only — isf","outputs":[{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_plasma_nM","label":"Mab plasma","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_isf_nM","label":"Mab isf","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"target_isf_pct_baseline","label":"Target isf pct baseline","unit":"dimensionless"}],"scenario_id":"transient-driver-only-isf","scientific_questions":["How do the model's key biological readouts change under transient driver only — isf?"],"time_span":{"end":1344,"start":0,"step":12}},{"controls":[],"description":"Specified fixed initial drivers, local protein/target concentrations and hour calendar; no administered dose events.","interpretation_guardrails":["Three independent local concentration systems represent plasma, brain interstitial fluid and CSF. There are no inter-space flows or compartment volumes.","Transient, durable and lagged expression drivers are dimensionless authored inputs; they are not measured vector copies, administered vector doses or observed nuclear DNA.","Profile route, dose and serotype labels identify fixed authored initial-condition sets. No administration, dose-to-transduction or vector transport law is represented.","Production scales, effective loss rates and initial drivers are authored conditional inputs; original profile fitting is outside this scope.","Human binding affinity is assumed for rat. Target baselines are primary-model equilibrium predictions used as specified setpoints, not independent measured concentrations.","A common effective target-turnover closure and a single-stage expression lag are declared assumptions.","Each complex contains one antibody and one target. Accounting remains a local concentration balance; no cross-space mass or volume-weighted conservation is asserted.","Forty read-only primary reference facts provide context and do not enter the companion equations or represent additional simulated observations.","No whole-primary-model, published-figure, sampled-population, clinical translation, immunogenicity or gene-delivery optimization result is assigned."],"name":"Transient driver only — csf","outputs":[{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_plasma_nM","label":"Mab plasma","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_isf_nM","label":"Mab isf","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"target_isf_pct_baseline","label":"Target isf pct baseline","unit":"dimensionless"}],"scenario_id":"transient-driver-only-csf","scientific_questions":["How do the model's key biological readouts change under transient driver only — csf?"],"time_span":{"end":1344,"start":0,"step":12}},{"controls":[],"description":"Specified fixed initial drivers, local protein/target concentrations and hour calendar; no administered dose events.","interpretation_guardrails":["Three independent local concentration systems represent plasma, brain interstitial fluid and CSF. There are no inter-space flows or compartment volumes.","Transient, durable and lagged expression drivers are dimensionless authored inputs; they are not measured vector copies, administered vector doses or observed nuclear DNA.","Profile route, dose and serotype labels identify fixed authored initial-condition sets. No administration, dose-to-transduction or vector transport law is represented.","Production scales, effective loss rates and initial drivers are authored conditional inputs; original profile fitting is outside this scope.","Human binding affinity is assumed for rat. Target baselines are primary-model equilibrium predictions used as specified setpoints, not independent measured concentrations.","A common effective target-turnover closure and a single-stage expression lag are declared assumptions.","Each complex contains one antibody and one target. Accounting remains a local concentration balance; no cross-space mass or volume-weighted conservation is asserted.","Forty read-only primary reference facts provide context and do not enter the companion equations or represent additional simulated observations.","No whole-primary-model, published-figure, sampled-population, clinical translation, immunogenicity or gene-delivery optimization result is assigned."],"name":"Initial plasma antibody — target binding control","outputs":[{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_plasma_nM","label":"Mab plasma","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"mab_isf_nM","label":"Mab isf","unit":"nM"},{"classification":"provisional","description":"Declared local concentration, dimensionless driver, flux or nonfeedback accounting quantity.","key":"target_isf_pct_baseline","label":"Target isf pct baseline","unit":"dimensionless"}],"scenario_id":"initial-antibody-plasma","scientific_questions":["How do the model's key biological readouts change under initial plasma antibody — target binding control?"],"time_span":{"end":1344,"start":0,"step":12}}],"targets":[{"key":"targetx","label":"TargetX (anonymized target)","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s10928-026-10051-w","locator":"Primary-reference pharmacological or study context; 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It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"40 kg — approved, 1 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-1p0-40kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 40 kg — approved, 1 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"40 kg — alternative, 1 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-1p0-40kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 40 kg — alternative, 1 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"40 kg — approved, 0.75 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-0p75-40kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 40 kg — approved, 0.75 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"40 kg — alternative, 0.75 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-0p75-40kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 40 kg — alternative, 0.75 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"40 kg — approved, 0.5 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-0p5-40kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 40 kg — approved, 0.5 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"40 kg — alternative, 0.5 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-0p5-40kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 40 kg — alternative, 0.5 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"50 kg — approved, 1.25 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-1p25-50kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 50 kg — approved, 1.25 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"50 kg — alternative, 1.25 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-1p25-50kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 50 kg — alternative, 1.25 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"50 kg — approved, 1 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-1p0-50kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 50 kg — approved, 1 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"50 kg — alternative, 1 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-1p0-50kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 50 kg — alternative, 1 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"50 kg — approved, 0.75 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-0p75-50kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 50 kg — approved, 0.75 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"50 kg — alternative, 0.75 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-0p75-50kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 50 kg — alternative, 0.75 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"50 kg — approved, 0.5 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-0p5-50kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 50 kg — approved, 0.5 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"50 kg — alternative, 0.5 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-0p5-50kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 50 kg — alternative, 0.5 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"60 kg — approved, 1.25 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-1p25-60kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 60 kg — approved, 1.25 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"60 kg — alternative, 1.25 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-1p25-60kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 60 kg — alternative, 1.25 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"60 kg — approved, 1 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-1p0-60kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 60 kg — approved, 1 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"60 kg — alternative, 1 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-1p0-60kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 60 kg — alternative, 1 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"60 kg — approved, 0.75 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-0p75-60kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 60 kg — approved, 0.75 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"60 kg — alternative, 0.75 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-0p75-60kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 60 kg — alternative, 0.75 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"60 kg — approved, 0.5 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-0p5-60kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 60 kg — approved, 0.5 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"60 kg — alternative, 0.5 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-0p5-60kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 60 kg — alternative, 0.5 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"70 kg — approved, 1.25 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-1p25-70kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 70 kg — approved, 1.25 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"70 kg — alternative, 1.25 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-1p25-70kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 70 kg — alternative, 1.25 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"70 kg — approved, 1 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-1p0-70kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 70 kg — approved, 1 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"70 kg — alternative, 1 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-1p0-70kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 70 kg — alternative, 1 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"70 kg — approved, 0.75 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-0p75-70kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 70 kg — approved, 0.75 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"70 kg — alternative, 0.75 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-0p75-70kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 70 kg — alternative, 0.75 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"70 kg — approved, 0.5 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-0p5-70kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 70 kg — approved, 0.5 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"70 kg — alternative, 0.5 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-0p5-70kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 70 kg — alternative, 0.5 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"85 kg — approved, 1.25 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-1p25-85kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 85 kg — approved, 1.25 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"85 kg — alternative, 1.25 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-1p25-85kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 85 kg — alternative, 1.25 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"85 kg — approved, 1 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-1p0-85kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 85 kg — approved, 1 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"85 kg — alternative, 1 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-1p0-85kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 85 kg — alternative, 1 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"85 kg — approved, 0.75 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-0p75-85kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 85 kg — approved, 0.75 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"85 kg — alternative, 0.75 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-0p75-85kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 85 kg — alternative, 0.75 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"85 kg — approved, 0.5 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-0p5-85kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 85 kg — approved, 0.5 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"85 kg — alternative, 0.5 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-0p5-85kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 85 kg — alternative, 0.5 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"97 kg — approved, 1.25 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-1p25-97kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 97 kg — approved, 1.25 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"97 kg — alternative, 1.25 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-1p25-97kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 97 kg — alternative, 1.25 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"97 kg — approved, 1 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-1p0-97kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 97 kg — approved, 1 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"97 kg — alternative, 1 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-1p0-97kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 97 kg — alternative, 1 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"97 kg — approved, 0.75 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-0p75-97kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 97 kg — approved, 0.75 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"97 kg — alternative, 0.75 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-0p75-97kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 97 kg — alternative, 0.75 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. 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It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"97 kg — alternative, 0.5 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-0p5-97kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 97 kg — alternative, 0.5 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"110 kg — approved, 1.25 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"approved-1p25-110kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 110 kg — approved, 1.25 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}},{"controls":[],"description":"Fixed-input intact-ADC trajectory under the declared monotherapy schedule.","interpretation_guardrails":["Conditional fixed-input intact-ADC exposure, with individual deviations fixed to zero in the supplied contexts.","The 500-person source demographic sample and original random draws are unavailable; reference trajectories are not population geometric means, CVs or equivalence results.","All administrations use the monotherapy schedule: days 1, 8 and 15 of each 28-day cycle, represented at hours 0, 168 and 336 within each cycle; 30-minute infusions.","The first-cycle observer stops at 672 h; the late observer starts at 6048 h and is read at the fixed 6720 h endpoint. It does not stop automatically if the horizon is extended.","The late window corresponds to days 252–280; it is not initialized at an exact periodic steady state.","Weight-band probes use interior weights because the publication does not determine every shared boundary inclusion.","The 110 kg probes use the explicitly reported initial 1.25 mg/kg cap of 125 mg; no reduced-tier high-weight cap is inferred.","Dose amounts and body weight are frozen together; changing weight requires rebuilding both PK inputs and the corresponding administration amounts.","No unconjugated payload, antitumor response, toxicity or clinical dosing recommendation is calculated."],"name":"110 kg — alternative, 1.25 mg/kg tier","outputs":[{"classification":"provisional","description":"Central concentration over the selected simulation window.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"AUC first over the selected simulation window.","key":"auc_first_mg_h_l","label":"AUC first","unit":"mg*h/L"},{"classification":"provisional","description":"AUC late over the selected simulation window.","key":"auc_late_mg_h_l","label":"AUC late","unit":"mg*h/L"},{"classification":"provisional","description":"Accounted amount over the selected simulation window.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"alternative-1p25-110kg-280d-full-ode","scientific_questions":["How do the model's key biological readouts change under 110 kg — alternative, 1.25 mg/kg tier?"],"time_span":{"end":6720,"start":0,"step":24}}],"targets":[{"key":"nectin4","label":"Nectin-4","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s00280-025-04764-x","locator":"Primary-reference pharmacological or study context; authored card and source-review context.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"therapeutics":[{"key":"enfortumab_vedotin","label":"Enfortumab vedotin"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.1.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"Six fixed references combine supplied apparent one-compartment PK with an independent exponential C5 coordinate, separate drug and concentration-coordinate accounting, and explicit nominal calendars.","diseases":[{"key":"neuromyelitis_optica_spectrum_disorder","label":"Neuromyelitis optica spectrum disorder","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.3389/fneur.2024.1332890","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"links":{"page":"/modeling/models/ortiz-2024-ravulizumab-nmosd-pkpd","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":null,"model_classes":["Conditional fixed one-compartment PK","Independent autonomous decay coordinate"],"model_id":"ortiz_2024_ravulizumab_nmosd_pkpd","name":"Ravulizumab PK and independent C5 decay coordinates","outputs":[{"description":"Conditional serum PK concentration","key":"ravulizumab_concentration_ug_ml","label":"Ravulizumab concentration","unit":"ug/mL"},{"description":"Exact retained coordinate/readout alias of the fixed mathematical reference.","key":"free_c5_ug_ml","label":"Free C5","unit":"ug/mL"},{"description":"Current plus eliminated apparent drug amount","key":"accounted_drug_mg","label":"Accounted drug","unit":"mg"},{"description":"Independent concentration-coordinate accounting; not a binding mass balance","key":"accounted_c5_coordinate_ug_ml","label":"Accounted C5 coordinate","unit":"ug/mL"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Fixed one-compartment apparent PK and independent autonomous C5 decay coordinate under a supplied bolus calendar. 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Drug mass usesmg and target accounting usesnmol; they must not be added together.","Antibody149kDareferenceisassumed; target40000ng/LpernM follows reported dual-unit baseline.","Target-turnover half-time is not drug terminal half-life."],"name":"5 mg/kg every 2 weeks,90 then 60-minute infusions","outputs":[{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"total_bevacizumab_mg_L","label":"Total bevacizumab","unit":null},{"classification":"provisional","description":"Free serum VEGF165 model readout.","key":"free_vegf165_ng_L","label":"Free VEGF165","unit":"ng/L"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_bevacizumab_mg","label":"Accounted bevacizumab","unit":"mg"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_target_nmol","label":"Accounted target","unit":"nmol"}],"scenario_id":"fixed_5mgkg_q2w_90_then_60min","scientific_questions":["How do the model's key biological readouts change under 5 mg/kg every 2 weeks,90 then 60-minute infusions?"],"time_span":{"end":126,"start":0,"step":1}},{"controls":[],"description":"Specified deterministic infusion and fixed-covariate history.","interpretation_guardrails":["Deterministic fixed histories only; no original individual fitting, sampled populations or clinical dose selection.","Body weight and allometric coefficients stay fixed. Clearances scale with weight exponent0.75 and volumes with exponent1 relative to70kg.","Infusion durations are explicit chosen histories, not recovered individual infusion records.","All accounting and elapsed-time states are nonfeedback observers. AUC keeps physical mg*day/L under alternate hour display.","No claim of published figure-panel, population, residual-error or genotype-effect reconstruction.","Free central drug, free target and effective1:1complex are algebraic QSS quantities, not kon/koff kinetic states.","The apparent peripheral pool carries free drug and is not a separately sampled serum compartment.","CLRC=CL is fixed. Drug mass usesmg and target accounting usesnmol; they must not be added together.","Antibody149kDareferenceisassumed; target40000ng/LpernM follows reported dual-unit baseline.","Target-turnover half-time is not drug terminal half-life."],"name":"5 mg/kg every 2 weeks,90 then 30-minute infusions","outputs":[{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"total_bevacizumab_mg_L","label":"Total bevacizumab","unit":null},{"classification":"provisional","description":"Free serum VEGF165 model readout.","key":"free_vegf165_ng_L","label":"Free VEGF165","unit":"ng/L"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_bevacizumab_mg","label":"Accounted bevacizumab","unit":"mg"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_target_nmol","label":"Accounted target","unit":"nmol"}],"scenario_id":"fixed_5mgkg_q2w_90_then_30min","scientific_questions":["How do the model's key biological readouts change under 5 mg/kg every 2 weeks,90 then 30-minute infusions?"],"time_span":{"end":126,"start":0,"step":1}},{"controls":[],"description":"Specified deterministic infusion and fixed-covariate history.","interpretation_guardrails":["Deterministic fixed histories only; no original individual fitting, sampled populations or clinical dose selection.","Body weight and allometric coefficients stay fixed. Clearances scale with weight exponent0.75 and volumes with exponent1 relative to70kg.","Infusion durations are explicit chosen histories, not recovered individual infusion records.","All accounting and elapsed-time states are nonfeedback observers. AUC keeps physical mg*day/L under alternate hour display.","No claim of published figure-panel, population, residual-error or genotype-effect reconstruction.","Free central drug, free target and effective1:1complex are algebraic QSS quantities, not kon/koff kinetic states.","The apparent peripheral pool carries free drug and is not a separately sampled serum compartment.","CLRC=CL is fixed. Drug mass usesmg and target accounting usesnmol; they must not be added together.","Antibody149kDareferenceisassumed; target40000ng/LpernM follows reported dual-unit baseline.","Target-turnover half-time is not drug terminal half-life."],"name":"10 mg/kg every 2 weeks,85-minute fixed infusions","outputs":[{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"total_bevacizumab_mg_L","label":"Total bevacizumab","unit":null},{"classification":"provisional","description":"Free serum VEGF165 model readout.","key":"free_vegf165_ng_L","label":"Free VEGF165","unit":"ng/L"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_bevacizumab_mg","label":"Accounted bevacizumab","unit":"mg"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_target_nmol","label":"Accounted target","unit":"nmol"}],"scenario_id":"fixed_10mgkg_q2w_85min","scientific_questions":["How do the model's key biological readouts change under 10 mg/kg every 2 weeks,85-minute fixed infusions?"],"time_span":{"end":126,"start":0,"step":1}},{"controls":[],"description":"Specified deterministic infusion and fixed-covariate history.","interpretation_guardrails":["Deterministic fixed histories only; no original individual fitting, sampled populations or clinical dose selection.","Body weight and allometric coefficients stay fixed. Clearances scale with weight exponent0.75 and volumes with exponent1 relative to70kg.","Infusion durations are explicit chosen histories, not recovered individual infusion records.","All accounting and elapsed-time states are nonfeedback observers. AUC keeps physical mg*day/L under alternate hour display.","No claim of published figure-panel, population, residual-error or genotype-effect reconstruction.","Free central drug, free target and effective1:1complex are algebraic QSS quantities, not kon/koff kinetic states.","The apparent peripheral pool carries free drug and is not a separately sampled serum compartment.","CLRC=CL is fixed. Drug mass usesmg and target accounting usesnmol; they must not be added together.","Antibody149kDareferenceisassumed; target40000ng/LpernM follows reported dual-unit baseline.","Target-turnover half-time is not drug terminal half-life."],"name":"5 mg/kg every 2 weeks, 50 kg,85-minute fixed infusions","outputs":[{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"total_bevacizumab_mg_L","label":"Total bevacizumab","unit":null},{"classification":"provisional","description":"Free serum VEGF165 model readout.","key":"free_vegf165_ng_L","label":"Free VEGF165","unit":"ng/L"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_bevacizumab_mg","label":"Accounted bevacizumab","unit":"mg"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_target_nmol","label":"Accounted target","unit":"nmol"}],"scenario_id":"fixed_5mgkg_q2w_50kg_85min","scientific_questions":["How do the model's key biological readouts change under 5 mg/kg every 2 weeks, 50 kg,85-minute fixed infusions?"],"time_span":{"end":126,"start":0,"step":1}},{"controls":[],"description":"Specified deterministic infusion and fixed-covariate history.","interpretation_guardrails":["Deterministic fixed histories only; no original individual fitting, sampled populations or clinical dose selection.","Body weight and allometric coefficients stay fixed. Clearances scale with weight exponent0.75 and volumes with exponent1 relative to70kg.","Infusion durations are explicit chosen histories, not recovered individual infusion records.","All accounting and elapsed-time states are nonfeedback observers. AUC keeps physical mg*day/L under alternate hour display.","No claim of published figure-panel, population, residual-error or genotype-effect reconstruction.","Free central drug, free target and effective1:1complex are algebraic QSS quantities, not kon/koff kinetic states.","The apparent peripheral pool carries free drug and is not a separately sampled serum compartment.","CLRC=CL is fixed. Drug mass usesmg and target accounting usesnmol; they must not be added together.","Antibody149kDareferenceisassumed; target40000ng/LpernM follows reported dual-unit baseline.","Target-turnover half-time is not drug terminal half-life."],"name":"5 mg/kg every 2 weeks, 94 kg,85-minute fixed infusions","outputs":[{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"total_bevacizumab_mg_L","label":"Total bevacizumab","unit":null},{"classification":"provisional","description":"Free serum VEGF165 model readout.","key":"free_vegf165_ng_L","label":"Free VEGF165","unit":"ng/L"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_bevacizumab_mg","label":"Accounted bevacizumab","unit":"mg"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_target_nmol","label":"Accounted target","unit":"nmol"}],"scenario_id":"fixed_5mgkg_q2w_94kg_85min","scientific_questions":["How do the model's key biological readouts change under 5 mg/kg every 2 weeks, 94 kg,85-minute fixed infusions?"],"time_span":{"end":126,"start":0,"step":1}},{"controls":[],"description":"Specified deterministic infusion and fixed-covariate history.","interpretation_guardrails":["Deterministic fixed histories only; no original individual fitting, sampled populations or clinical dose selection.","Body weight and allometric coefficients stay fixed. Clearances scale with weight exponent0.75 and volumes with exponent1 relative to70kg.","Infusion durations are explicit chosen histories, not recovered individual infusion records.","All accounting and elapsed-time states are nonfeedback observers. AUC keeps physical mg*day/L under alternate hour display.","No claim of published figure-panel, population, residual-error or genotype-effect reconstruction.","Free central drug, free target and effective1:1complex are algebraic QSS quantities, not kon/koff kinetic states.","The apparent peripheral pool carries free drug and is not a separately sampled serum compartment.","CLRC=CL is fixed. Drug mass usesmg and target accounting usesnmol; they must not be added together.","Antibody149kDareferenceisassumed; target40000ng/LpernM follows reported dual-unit baseline.","Target-turnover half-time is not drug terminal half-life."],"name":"Untreated target equilibrium","outputs":[{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"total_bevacizumab_mg_L","label":"Total bevacizumab","unit":null},{"classification":"provisional","description":"Free serum VEGF165 model readout.","key":"free_vegf165_ng_L","label":"Free VEGF165","unit":"ng/L"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_bevacizumab_mg","label":"Accounted bevacizumab","unit":"mg"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_target_nmol","label":"Accounted target","unit":"nmol"}],"scenario_id":"untreated_target_equilibrium","scientific_questions":["How do the model's key biological readouts change under untreated target equilibrium?"],"time_span":{"end":126,"start":0,"step":1}},{"controls":[],"description":"Specified deterministic infusion and fixed-covariate history.","interpretation_guardrails":["Deterministic fixed histories only; no original individual fitting, sampled populations or clinical dose selection.","Body weight and allometric coefficients stay fixed. Clearances scale with weight exponent0.75 and volumes with exponent1 relative to70kg.","Infusion durations are explicit chosen histories, not recovered individual infusion records.","All accounting and elapsed-time states are nonfeedback observers. AUC keeps physical mg*day/L under alternate hour display.","No claim of published figure-panel, population, residual-error or genotype-effect reconstruction.","Free central drug, free target and effective1:1complex are algebraic QSS quantities, not kon/koff kinetic states.","The apparent peripheral pool carries free drug and is not a separately sampled serum compartment.","CLRC=CL is fixed. Drug mass usesmg and target accounting usesnmol; they must not be added together.","Antibody149kDareferenceisassumed; target40000ng/LpernM follows reported dual-unit baseline.","Target-turnover half-time is not drug terminal half-life."],"name":"Specified doubled target baseline with 5 mg/kg every 2 weeks","outputs":[{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"total_bevacizumab_mg_L","label":"Total bevacizumab","unit":null},{"classification":"provisional","description":"Free serum VEGF165 model readout.","key":"free_vegf165_ng_L","label":"Free VEGF165","unit":"ng/L"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_bevacizumab_mg","label":"Accounted bevacizumab","unit":"mg"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_target_nmol","label":"Accounted target","unit":"nmol"}],"scenario_id":"fixed_double_target_baseline_5mgkg_q2w","scientific_questions":["How do the model's key biological readouts change under specified doubled target baseline with 5 mg/kg every 2 weeks?"],"time_span":{"end":126,"start":0,"step":1}},{"controls":[],"description":"Specified deterministic infusion and fixed-covariate history.","interpretation_guardrails":["Deterministic fixed histories only; no original individual fitting, sampled populations or clinical dose selection.","Body weight and allometric coefficients stay fixed. Clearances scale with weight exponent0.75 and volumes with exponent1 relative to70kg.","Infusion durations are explicit chosen histories, not recovered individual infusion records.","All accounting and elapsed-time states are nonfeedback observers. AUC keeps physical mg*day/L under alternate hour display.","No claim of published figure-panel, population, residual-error or genotype-effect reconstruction.","Free central drug, free target and effective1:1complex are algebraic QSS quantities, not kon/koff kinetic states.","The apparent peripheral pool carries free drug and is not a separately sampled serum compartment.","CLRC=CL is fixed. Drug mass usesmg and target accounting usesnmol; they must not be added together.","Antibody149kDareferenceisassumed; target40000ng/LpernM follows reported dual-unit baseline.","Target-turnover half-time is not drug terminal half-life."],"name":"Fixed 70 kg, 5 mg/kg,90-minute infusion history to 83.55 days","outputs":[{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"total_bevacizumab_mg_L","label":"Total bevacizumab","unit":null},{"classification":"provisional","description":"Free serum VEGF165 model readout.","key":"free_vegf165_ng_L","label":"Free VEGF165","unit":"ng/L"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_bevacizumab_mg","label":"Accounted bevacizumab","unit":"mg"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_target_nmol","label":"Accounted target","unit":"nmol"}],"scenario_id":"fixed_vignette_six_doses_83p55day","scientific_questions":["How do the model's key biological readouts change under fixed 70 kg, 5 mg/kg,90-minute infusion history to 83.55 days?"],"time_span":{"end":83.55,"start":0,"step":83.55}},{"controls":[],"description":"Specified deterministic infusion and fixed-covariate history.","interpretation_guardrails":["Deterministic fixed histories only; no original individual fitting, sampled populations or clinical dose selection.","Body weight and allometric coefficients stay fixed. Clearances scale with weight exponent0.75 and volumes with exponent1 relative to70kg.","Infusion durations are explicit chosen histories, not recovered individual infusion records.","All accounting and elapsed-time states are nonfeedback observers. AUC keeps physical mg*day/L under alternate hour display.","No claim of published figure-panel, population, residual-error or genotype-effect reconstruction.","Free central drug, free target and effective1:1complex are algebraic QSS quantities, not kon/koff kinetic states.","The apparent peripheral pool carries free drug and is not a separately sampled serum compartment.","CLRC=CL is fixed. Drug mass usesmg and target accounting usesnmol; they must not be added together.","Antibody149kDareferenceisassumed; target40000ng/LpernM follows reported dual-unit baseline.","Target-turnover half-time is not drug terminal half-life."],"name":"Fixed 70 kg, 5 mg/kg,90-minute infusion history to 14.0 days","outputs":[{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"total_bevacizumab_mg_L","label":"Total bevacizumab","unit":null},{"classification":"provisional","description":"Free serum VEGF165 model readout.","key":"free_vegf165_ng_L","label":"Free VEGF165","unit":"ng/L"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_bevacizumab_mg","label":"Accounted bevacizumab","unit":"mg"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_target_nmol","label":"Accounted target","unit":"nmol"}],"scenario_id":"fixed_vignette_single_dose_14day","scientific_questions":["How do the model's key biological readouts change under fixed 70 kg, 5 mg/kg,90-minute infusion history to 14.0 days?"],"time_span":{"end":14,"start":0,"step":14}},{"controls":[],"description":"Specified deterministic infusion and fixed-covariate history.","interpretation_guardrails":["Deterministic fixed histories only; no original individual fitting, sampled populations or clinical dose selection.","Body weight and allometric coefficients stay fixed. Clearances scale with weight exponent0.75 and volumes with exponent1 relative to70kg.","Infusion durations are explicit chosen histories, not recovered individual infusion records.","All accounting and elapsed-time states are nonfeedback observers. AUC keeps physical mg*day/L under alternate hour display.","No claim of published figure-panel, population, residual-error or genotype-effect reconstruction.","Free central drug, free target and effective1:1complex are algebraic QSS quantities, not kon/koff kinetic states.","The apparent peripheral pool carries free drug and is not a separately sampled serum compartment.","CLRC=CL is fixed. Drug mass usesmg and target accounting usesnmol; they must not be added together.","Antibody149kDareferenceisassumed; target40000ng/LpernM follows reported dual-unit baseline.","Target-turnover half-time is not drug terminal half-life."],"name":"Fixed 70 kg, 5 mg/kg,90-minute infusion history to 59.55 days","outputs":[{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"total_bevacizumab_mg_L","label":"Total bevacizumab","unit":null},{"classification":"provisional","description":"Free serum VEGF165 model readout.","key":"free_vegf165_ng_L","label":"Free VEGF165","unit":"ng/L"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_bevacizumab_mg","label":"Accounted bevacizumab","unit":"mg"},{"classification":"provisional","description":"Specified fixed-context quantity, unit coordinate or accounting readout.","key":"accounted_target_nmol","label":"Accounted target","unit":"nmol"}],"scenario_id":"fixed_vignette_single_recovery_59p55day","scientific_questions":["How do the model's key biological readouts change under fixed 70 kg, 5 mg/kg,90-minute infusion history to 59.55 days?"],"time_span":{"end":59.55,"start":0,"step":59.55}}],"targets":[{"key":"vegfa","label":"VEGFA","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s00280-015-2701-3","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}},{"key":"vegf165","label":"VEGF165","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s00280-015-2701-3","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}},{"key":"vascular_endothelial_growth_factor_a","label":"vascular endothelial growth factor A","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s00280-015-2701-3","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"therapeutics":[{"key":"bevacizumab","label":"Bevacizumab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.3.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"Coupled two-compartment rituximab PK, gammaglobulin turnover and two-coordinate ANCA feedback.","diseases":[{"key":"anca_associated_vasculitis","label":"ANCA-associated vasculitis"}],"links":{"page":"/modeling/models/pasquiers-2025-rituximab-anca-gammaglobulin-pkpd","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"monoclonal antibody","model_classes":["joint rituximab PK/ANCA/gammaglobulin PD","conditional fixed-effect projections"],"model_id":"pasquiers_2025_rituximab_anca_gammaglobulin_pkpd","name":"Rituximab, ANCA and gammaglobulin turnover","outputs":[{"description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"description":"Gg g over the selected simulation window.","key":"gg_g_l","label":"Gg g","unit":"g/L"},{"description":"Anca blood u over the selected simulation window.","key":"anca_blood_u_ml","label":"Anca blood u","unit":"count/mL"},{"description":"Anca baseline fraction over the selected simulation window.","key":"anca_baseline_fraction","label":"Anca baseline fraction","unit":"dimensionless"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Conditional reference-covariate trajectory with one-hour infusions and a30day month convention.","interpretation_guardrails":["Conditional fixed-effect joint PK/PD, with no individual random deviations or residual observation noise.","Reference covariates follow Supplement S5: age52years, weight68kg, CRP11mg/L; sex is male unless explicitly changed.","Both ANCA compartments start at the CRP-conditioned baseline, and gammaglobulins start at their baseline. These coupled initial values are frozen with their inputs.","A month is represented by30days, an authored calendar convention. One-hour infusions follow the cohort methods; nominal event arrays do not reconstruct individual records.","The 375mg/m2 amount is667.5mg at the frozen1.78m2 administration reference; another BSA requires dose recalculation.","ANCA U/mL is a source assay calibration coordinate. The typed count/mL unit retains its numerical scale and is not a molecular count or enzyme-activity unit.","ANCA production is a latent model coordinate, not a directly measured blood compartment.","Published population medians, percentiles and threshold probabilities do not become conditional trajectory targets.","Clinical utility, infection/relapse risk, statistical fitting and the original1000-person simulation are not reconstructed."],"name":"induction 375mgm2 q1w 6mo — MPO","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Gg g over the selected simulation window.","key":"gg_g_l","label":"Gg g","unit":"g/L"},{"classification":"provisional","description":"Anca blood u over the selected simulation window.","key":"anca_blood_u_ml","label":"Anca blood u","unit":"count/mL"},{"classification":"provisional","description":"Anca baseline fraction over the selected simulation window.","key":"anca_baseline_fraction","label":"Anca baseline fraction","unit":"dimensionless"}],"scenario_id":"induction-375mgm2-q1w-6mo-mpo","scientific_questions":["How do the model's key biological readouts change under induction 375mgm2 q1w 6mo — mpo?"],"time_span":{"end":180,"start":0,"step":1}},{"controls":[],"description":"Conditional reference-covariate trajectory with one-hour infusions and a30day month convention.","interpretation_guardrails":["Conditional fixed-effect joint PK/PD, with no individual random deviations or residual observation noise.","Reference covariates follow Supplement S5: age52years, weight68kg, CRP11mg/L; sex is male unless explicitly changed.","Both ANCA compartments start at the CRP-conditioned baseline, and gammaglobulins start at their baseline. These coupled initial values are frozen with their inputs.","A month is represented by30days, an authored calendar convention. One-hour infusions follow the cohort methods; nominal event arrays do not reconstruct individual records.","The 375mg/m2 amount is667.5mg at the frozen1.78m2 administration reference; another BSA requires dose recalculation.","ANCA U/mL is a source assay calibration coordinate. The typed count/mL unit retains its numerical scale and is not a molecular count or enzyme-activity unit.","ANCA production is a latent model coordinate, not a directly measured blood compartment.","Published population medians, percentiles and threshold probabilities do not become conditional trajectory targets.","Clinical utility, infection/relapse risk, statistical fitting and the original1000-person simulation are not reconstructed."],"name":"induction 375mgm2 q1w 6mo — PR3","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Gg g over the selected simulation window.","key":"gg_g_l","label":"Gg g","unit":"g/L"},{"classification":"provisional","description":"Anca blood u over the selected simulation window.","key":"anca_blood_u_ml","label":"Anca blood u","unit":"count/mL"},{"classification":"provisional","description":"Anca baseline fraction over the selected simulation window.","key":"anca_baseline_fraction","label":"Anca baseline fraction","unit":"dimensionless"}],"scenario_id":"induction-375mgm2-q1w-6mo-pr3","scientific_questions":["How do the model's key biological readouts change under induction 375mgm2 q1w 6mo — pr3?"],"time_span":{"end":180,"start":0,"step":1}},{"controls":[],"description":"Conditional reference-covariate trajectory with one-hour infusions and a30day month convention.","interpretation_guardrails":["Conditional fixed-effect joint PK/PD, with no individual random deviations or residual observation noise.","Reference covariates follow Supplement S5: age52years, weight68kg, CRP11mg/L; sex is male unless explicitly changed.","Both ANCA compartments start at the CRP-conditioned baseline, and gammaglobulins start at their baseline. These coupled initial values are frozen with their inputs.","A month is represented by30days, an authored calendar convention. One-hour infusions follow the cohort methods; nominal event arrays do not reconstruct individual records.","The 375mg/m2 amount is667.5mg at the frozen1.78m2 administration reference; another BSA requires dose recalculation.","ANCA U/mL is a source assay calibration coordinate. The typed count/mL unit retains its numerical scale and is not a molecular count or enzyme-activity unit.","ANCA production is a latent model coordinate, not a directly measured blood compartment.","Published population medians, percentiles and threshold probabilities do not become conditional trajectory targets.","Clinical utility, infection/relapse risk, statistical fitting and the original1000-person simulation are not reconstructed."],"name":"induction 1000mg d0 d14 6mo — MPO","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Gg g over the selected simulation window.","key":"gg_g_l","label":"Gg g","unit":"g/L"},{"classification":"provisional","description":"Anca blood u over the selected simulation window.","key":"anca_blood_u_ml","label":"Anca blood u","unit":"count/mL"},{"classification":"provisional","description":"Anca baseline fraction over the selected simulation window.","key":"anca_baseline_fraction","label":"Anca baseline fraction","unit":"dimensionless"}],"scenario_id":"induction-1000mg-d0-d14-6mo-mpo","scientific_questions":["How do the model's key biological readouts change under induction 1000mg d0 d14 6mo — mpo?"],"time_span":{"end":180,"start":0,"step":1}},{"controls":[],"description":"Conditional reference-covariate trajectory with one-hour infusions and a30day month convention.","interpretation_guardrails":["Conditional fixed-effect joint PK/PD, with no individual random deviations or residual observation noise.","Reference covariates follow Supplement S5: age52years, weight68kg, CRP11mg/L; sex is male unless explicitly changed.","Both ANCA compartments start at the CRP-conditioned baseline, and gammaglobulins start at their baseline. These coupled initial values are frozen with their inputs.","A month is represented by30days, an authored calendar convention. One-hour infusions follow the cohort methods; nominal event arrays do not reconstruct individual records.","The 375mg/m2 amount is667.5mg at the frozen1.78m2 administration reference; another BSA requires dose recalculation.","ANCA U/mL is a source assay calibration coordinate. The typed count/mL unit retains its numerical scale and is not a molecular count or enzyme-activity unit.","ANCA production is a latent model coordinate, not a directly measured blood compartment.","Published population medians, percentiles and threshold probabilities do not become conditional trajectory targets.","Clinical utility, infection/relapse risk, statistical fitting and the original1000-person simulation are not reconstructed."],"name":"induction 1000mg d0 d14 6mo — PR3","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Gg g over the selected simulation window.","key":"gg_g_l","label":"Gg g","unit":"g/L"},{"classification":"provisional","description":"Anca blood u over the selected simulation window.","key":"anca_blood_u_ml","label":"Anca blood u","unit":"count/mL"},{"classification":"provisional","description":"Anca baseline fraction over the selected simulation window.","key":"anca_baseline_fraction","label":"Anca baseline fraction","unit":"dimensionless"}],"scenario_id":"induction-1000mg-d0-d14-6mo-pr3","scientific_questions":["How do the model's key biological readouts change under induction 1000mg d0 d14 6mo — pr3?"],"time_span":{"end":180,"start":0,"step":1}},{"controls":[],"description":"Conditional reference-covariate trajectory with one-hour infusions and a30day month convention.","interpretation_guardrails":["Conditional fixed-effect joint PK/PD, with no individual random deviations or residual observation noise.","Reference covariates follow Supplement S5: age52years, weight68kg, CRP11mg/L; sex is male unless explicitly changed.","Both ANCA compartments start at the CRP-conditioned baseline, and gammaglobulins start at their baseline. These coupled initial values are frozen with their inputs.","A month is represented by30days, an authored calendar convention. One-hour infusions follow the cohort methods; nominal event arrays do not reconstruct individual records.","The 375mg/m2 amount is667.5mg at the frozen1.78m2 administration reference; another BSA requires dose recalculation.","ANCA U/mL is a source assay calibration coordinate. The typed count/mL unit retains its numerical scale and is not a molecular count or enzyme-activity unit.","ANCA production is a latent model coordinate, not a directly measured blood compartment.","Published population medians, percentiles and threshold probabilities do not become conditional trajectory targets.","Clinical utility, infection/relapse risk, statistical fitting and the original1000-person simulation are not reconstructed."],"name":"maintenance 500mg q6m 24mo — MPO","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Gg g over the selected simulation window.","key":"gg_g_l","label":"Gg g","unit":"g/L"},{"classification":"provisional","description":"Anca blood u over the selected simulation window.","key":"anca_blood_u_ml","label":"Anca blood u","unit":"count/mL"},{"classification":"provisional","description":"Anca baseline fraction over the selected simulation window.","key":"anca_baseline_fraction","label":"Anca baseline fraction","unit":"dimensionless"}],"scenario_id":"maintenance-500mg-q6m-24mo-mpo","scientific_questions":["How do the model's key biological readouts change under maintenance 500mg q6m 24mo — mpo?"],"time_span":{"end":720,"start":0,"step":2}},{"controls":[],"description":"Conditional reference-covariate trajectory with one-hour infusions and a30day month convention.","interpretation_guardrails":["Conditional fixed-effect joint PK/PD, with no individual random deviations or residual observation noise.","Reference covariates follow Supplement S5: age52years, weight68kg, CRP11mg/L; sex is male unless explicitly changed.","Both ANCA compartments start at the CRP-conditioned baseline, and gammaglobulins start at their baseline. These coupled initial values are frozen with their inputs.","A month is represented by30days, an authored calendar convention. One-hour infusions follow the cohort methods; nominal event arrays do not reconstruct individual records.","The 375mg/m2 amount is667.5mg at the frozen1.78m2 administration reference; another BSA requires dose recalculation.","ANCA U/mL is a source assay calibration coordinate. The typed count/mL unit retains its numerical scale and is not a molecular count or enzyme-activity unit.","ANCA production is a latent model coordinate, not a directly measured blood compartment.","Published population medians, percentiles and threshold probabilities do not become conditional trajectory targets.","Clinical utility, infection/relapse risk, statistical fitting and the original1000-person simulation are not reconstructed."],"name":"maintenance 500mg q6m 24mo — PR3","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Gg g over the selected simulation window.","key":"gg_g_l","label":"Gg g","unit":"g/L"},{"classification":"provisional","description":"Anca blood u over the selected simulation window.","key":"anca_blood_u_ml","label":"Anca blood u","unit":"count/mL"},{"classification":"provisional","description":"Anca baseline fraction over the selected simulation window.","key":"anca_baseline_fraction","label":"Anca baseline fraction","unit":"dimensionless"}],"scenario_id":"maintenance-500mg-q6m-24mo-pr3","scientific_questions":["How do the model's key biological readouts change under maintenance 500mg q6m 24mo — pr3?"],"time_span":{"end":720,"start":0,"step":2}},{"controls":[],"description":"Conditional reference-covariate trajectory with one-hour infusions and a30day month convention.","interpretation_guardrails":["Conditional fixed-effect joint PK/PD, with no individual random deviations or residual observation noise.","Reference covariates follow Supplement S5: age52years, weight68kg, CRP11mg/L; sex is male unless explicitly changed.","Both ANCA compartments start at the CRP-conditioned baseline, and gammaglobulins start at their baseline. These coupled initial values are frozen with their inputs.","A month is represented by30days, an authored calendar convention. One-hour infusions follow the cohort methods; nominal event arrays do not reconstruct individual records.","The 375mg/m2 amount is667.5mg at the frozen1.78m2 administration reference; another BSA requires dose recalculation.","ANCA U/mL is a source assay calibration coordinate. The typed count/mL unit retains its numerical scale and is not a molecular count or enzyme-activity unit.","ANCA production is a latent model coordinate, not a directly measured blood compartment.","Published population medians, percentiles and threshold probabilities do not become conditional trajectory targets.","Clinical utility, infection/relapse risk, statistical fitting and the original1000-person simulation are not reconstructed."],"name":"maintenance 500mg q6m start4m 24mo — MPO","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Gg g over the selected simulation window.","key":"gg_g_l","label":"Gg g","unit":"g/L"},{"classification":"provisional","description":"Anca blood u over the selected simulation window.","key":"anca_blood_u_ml","label":"Anca blood u","unit":"count/mL"},{"classification":"provisional","description":"Anca baseline fraction over the selected simulation window.","key":"anca_baseline_fraction","label":"Anca baseline fraction","unit":"dimensionless"}],"scenario_id":"maintenance-500mg-q6m-start4m-24mo-mpo","scientific_questions":["How do the model's key biological readouts change under maintenance 500mg q6m start4m 24mo — mpo?"],"time_span":{"end":720,"start":0,"step":2}},{"controls":[],"description":"Conditional reference-covariate trajectory with one-hour infusions and a30day month convention.","interpretation_guardrails":["Conditional fixed-effect joint PK/PD, with no individual random deviations or residual observation noise.","Reference covariates follow Supplement S5: age52years, weight68kg, CRP11mg/L; sex is male unless explicitly changed.","Both ANCA compartments start at the CRP-conditioned baseline, and gammaglobulins start at their baseline. These coupled initial values are frozen with their inputs.","A month is represented by30days, an authored calendar convention. One-hour infusions follow the cohort methods; nominal event arrays do not reconstruct individual records.","The 375mg/m2 amount is667.5mg at the frozen1.78m2 administration reference; another BSA requires dose recalculation.","ANCA U/mL is a source assay calibration coordinate. The typed count/mL unit retains its numerical scale and is not a molecular count or enzyme-activity unit.","ANCA production is a latent model coordinate, not a directly measured blood compartment.","Published population medians, percentiles and threshold probabilities do not become conditional trajectory targets.","Clinical utility, infection/relapse risk, statistical fitting and the original1000-person simulation are not reconstructed."],"name":"maintenance 500mg q6m start4m 24mo — PR3","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Gg g over the selected simulation window.","key":"gg_g_l","label":"Gg g","unit":"g/L"},{"classification":"provisional","description":"Anca blood u over the selected simulation window.","key":"anca_blood_u_ml","label":"Anca blood u","unit":"count/mL"},{"classification":"provisional","description":"Anca baseline fraction over the selected simulation window.","key":"anca_baseline_fraction","label":"Anca baseline fraction","unit":"dimensionless"}],"scenario_id":"maintenance-500mg-q6m-start4m-24mo-pr3","scientific_questions":["How do the model's key biological readouts change under maintenance 500mg q6m start4m 24mo — pr3?"],"time_span":{"end":720,"start":0,"step":2}},{"controls":[],"description":"Conditional reference-covariate trajectory with one-hour infusions and a30day month convention.","interpretation_guardrails":["Conditional fixed-effect joint PK/PD, with no individual random deviations or residual observation noise.","Reference covariates follow Supplement S5: age52years, weight68kg, CRP11mg/L; sex is male unless explicitly changed.","Both ANCA compartments start at the CRP-conditioned baseline, and gammaglobulins start at their baseline. These coupled initial values are frozen with their inputs.","A month is represented by30days, an authored calendar convention. One-hour infusions follow the cohort methods; nominal event arrays do not reconstruct individual records.","The 375mg/m2 amount is667.5mg at the frozen1.78m2 administration reference; another BSA requires dose recalculation.","ANCA U/mL is a source assay calibration coordinate. The typed count/mL unit retains its numerical scale and is not a molecular count or enzyme-activity unit.","ANCA production is a latent model coordinate, not a directly measured blood compartment.","Published population medians, percentiles and threshold probabilities do not become conditional trajectory targets.","Clinical utility, infection/relapse risk, statistical fitting and the original1000-person simulation are not reconstructed."],"name":"maintenance 500mg q4m 24mo — MPO","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Gg g over the selected simulation window.","key":"gg_g_l","label":"Gg g","unit":"g/L"},{"classification":"provisional","description":"Anca blood u over the selected simulation window.","key":"anca_blood_u_ml","label":"Anca blood u","unit":"count/mL"},{"classification":"provisional","description":"Anca baseline fraction over the selected simulation window.","key":"anca_baseline_fraction","label":"Anca baseline fraction","unit":"dimensionless"}],"scenario_id":"maintenance-500mg-q4m-24mo-mpo","scientific_questions":["How do the model's key biological readouts change under maintenance 500mg q4m 24mo — mpo?"],"time_span":{"end":720,"start":0,"step":2}},{"controls":[],"description":"Conditional reference-covariate trajectory with one-hour infusions and a30day month convention.","interpretation_guardrails":["Conditional fixed-effect joint PK/PD, with no individual random deviations or residual observation noise.","Reference covariates follow Supplement S5: age52years, weight68kg, CRP11mg/L; sex is male unless explicitly changed.","Both ANCA compartments start at the CRP-conditioned baseline, and gammaglobulins start at their baseline. These coupled initial values are frozen with their inputs.","A month is represented by30days, an authored calendar convention. One-hour infusions follow the cohort methods; nominal event arrays do not reconstruct individual records.","The 375mg/m2 amount is667.5mg at the frozen1.78m2 administration reference; another BSA requires dose recalculation.","ANCA U/mL is a source assay calibration coordinate. The typed count/mL unit retains its numerical scale and is not a molecular count or enzyme-activity unit.","ANCA production is a latent model coordinate, not a directly measured blood compartment.","Published population medians, percentiles and threshold probabilities do not become conditional trajectory targets.","Clinical utility, infection/relapse risk, statistical fitting and the original1000-person simulation are not reconstructed."],"name":"maintenance 500mg q4m 24mo — PR3","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Gg g over the selected simulation window.","key":"gg_g_l","label":"Gg g","unit":"g/L"},{"classification":"provisional","description":"Anca blood u over the selected simulation window.","key":"anca_blood_u_ml","label":"Anca blood u","unit":"count/mL"},{"classification":"provisional","description":"Anca baseline fraction over the selected simulation window.","key":"anca_baseline_fraction","label":"Anca baseline fraction","unit":"dimensionless"}],"scenario_id":"maintenance-500mg-q4m-24mo-pr3","scientific_questions":["How do the model's key biological readouts change under maintenance 500mg q4m 24mo — pr3?"],"time_span":{"end":720,"start":0,"step":2}},{"controls":[],"description":"Conditional reference-covariate trajectory with one-hour infusions and a30day month convention.","interpretation_guardrails":["Conditional fixed-effect joint PK/PD, with no individual random deviations or residual observation noise.","Reference covariates follow Supplement S5: age52years, weight68kg, CRP11mg/L; sex is male unless explicitly changed.","Both ANCA compartments start at the CRP-conditioned baseline, and gammaglobulins start at their baseline. These coupled initial values are frozen with their inputs.","A month is represented by30days, an authored calendar convention. One-hour infusions follow the cohort methods; nominal event arrays do not reconstruct individual records.","The 375mg/m2 amount is667.5mg at the frozen1.78m2 administration reference; another BSA requires dose recalculation.","ANCA U/mL is a source assay calibration coordinate. The typed count/mL unit retains its numerical scale and is not a molecular count or enzyme-activity unit.","ANCA production is a latent model coordinate, not a directly measured blood compartment.","Published population medians, percentiles and threshold probabilities do not become conditional trajectory targets.","Clinical utility, infection/relapse risk, statistical fitting and the original1000-person simulation are not reconstructed."],"name":"maintenance 1000mg q4m 24mo — MPO","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Gg g over the selected simulation window.","key":"gg_g_l","label":"Gg g","unit":"g/L"},{"classification":"provisional","description":"Anca blood u over the selected simulation window.","key":"anca_blood_u_ml","label":"Anca blood u","unit":"count/mL"},{"classification":"provisional","description":"Anca baseline fraction over the selected simulation window.","key":"anca_baseline_fraction","label":"Anca baseline fraction","unit":"dimensionless"}],"scenario_id":"maintenance-1000mg-q4m-24mo-mpo","scientific_questions":["How do the model's key biological readouts change under maintenance 1000mg q4m 24mo — mpo?"],"time_span":{"end":720,"start":0,"step":2}},{"controls":[],"description":"Conditional reference-covariate trajectory with one-hour infusions and a30day month convention.","interpretation_guardrails":["Conditional fixed-effect joint PK/PD, with no individual random deviations or residual observation noise.","Reference covariates follow Supplement S5: age52years, weight68kg, CRP11mg/L; sex is male unless explicitly changed.","Both ANCA compartments start at the CRP-conditioned baseline, and gammaglobulins start at their baseline. These coupled initial values are frozen with their inputs.","A month is represented by30days, an authored calendar convention. One-hour infusions follow the cohort methods; nominal event arrays do not reconstruct individual records.","The 375mg/m2 amount is667.5mg at the frozen1.78m2 administration reference; another BSA requires dose recalculation.","ANCA U/mL is a source assay calibration coordinate. The typed count/mL unit retains its numerical scale and is not a molecular count or enzyme-activity unit.","ANCA production is a latent model coordinate, not a directly measured blood compartment.","Published population medians, percentiles and threshold probabilities do not become conditional trajectory targets.","Clinical utility, infection/relapse risk, statistical fitting and the original1000-person simulation are not reconstructed."],"name":"maintenance 1000mg q4m 24mo — PR3","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Gg g over the selected simulation window.","key":"gg_g_l","label":"Gg g","unit":"g/L"},{"classification":"provisional","description":"Anca blood u over the selected simulation window.","key":"anca_blood_u_ml","label":"Anca blood u","unit":"count/mL"},{"classification":"provisional","description":"Anca baseline fraction over the selected simulation window.","key":"anca_baseline_fraction","label":"Anca baseline fraction","unit":"dimensionless"}],"scenario_id":"maintenance-1000mg-q4m-24mo-pr3","scientific_questions":["How do the model's key biological readouts change under maintenance 1000mg q4m 24mo — pr3?"],"time_span":{"end":720,"start":0,"step":2}}],"targets":[{"key":"cd20","label":"CD20 / MS4A1","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1016/j.ebiom.2025.105989","locator":"Primary-reference pharmacological or study context; authored card and source-review context.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"therapeutics":[{"key":"rituximab","label":"Rituximab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.1.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"Explore treatment-driven peripheral immune recovery and CNS accumulation under explicitly defined continuous network configurations.","diseases":[{"key":"multiple_sclerosis_immune_network_exploration","label":"Multiple sclerosis immune-network exploration"}],"links":{"page":"/modeling/models/pernice-2023-greatnector-alemtuzumab-ms-petrinet-ode","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":null,"model_classes":["continuous Petri-net reconstruction","formal immune network"],"model_id":"pernice_2023_greatnector_alemtuzumab_ms_petrinet_ode","name":"Alemtuzumab and T-cell network recovery","outputs":[{"description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Declared continuous network context with formal model marking units and explicit pretreatment history.","interpretation_guardrails":["Continuous reconstruction with ordinary mass action x^m/m! and directly transcribed custom reaction rates; no stochastic distribution or fitted-patient replay.","State values are formal dimensionless model markings. Treatment is an abstract scaled marking, not mg, mol, concentration or receptor occupancy.","The colored configuration has self-Th17 passage kBBB*Th17^2/2 with net loss of one Th17 and entry of one CNS effector. Separate constitutive configurations add one to each pool at rate kBBB.","Both regulatory duplication transitions use peripheral Th1. Effector-antigen killing consumes both antigen and the effector; regulatory and treatment killing return their catalysts.","Raw day0 starts180days before treatment; full horizon2520days corresponds to clinical day−180..2340, including six months beyond the observed72month follow-up.","Two course-level marking jumps occur at raw days180/540. An additional what-if course occurs at1260; within-course daily administrations and infusion pharmacokinetics are not modeled.","The alternate forcing has a Gaussian input-rate envelope centered at raw1230days, width147days. Neither this center nor the integrated antigen maximum is asserted to match a clinical month30 peak.","CNS pools have no exit in the specified network. Their regularized ratio is an exploratory network proxy, not measured CNS damage or relapse probability.","The normalized immune denominator is positive in admitted contexts; a numerical zero extension does not define a new empty-system biological model.","No individual random effects, original clustering, calibration uncertainty, statistical likelihood or clinical optimization is reproduced."],"name":"Group 1 — common colored continuous configuration","outputs":[{"classification":"provisional","description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"classification":"provisional","description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"classification":"provisional","description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"classification":"provisional","description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"scenario_id":"msmp1","scientific_questions":["How do the model's key biological readouts change under group 1 — common colored continuous configuration?"],"time_span":{"end":2520,"start":0,"step":5}},{"controls":[],"description":"Declared continuous network context with formal model marking units and explicit pretreatment history.","interpretation_guardrails":["Continuous reconstruction with ordinary mass action x^m/m! and directly transcribed custom reaction rates; no stochastic distribution or fitted-patient replay.","State values are formal dimensionless model markings. Treatment is an abstract scaled marking, not mg, mol, concentration or receptor occupancy.","The colored configuration has self-Th17 passage kBBB*Th17^2/2 with net loss of one Th17 and entry of one CNS effector. Separate constitutive configurations add one to each pool at rate kBBB.","Both regulatory duplication transitions use peripheral Th1. Effector-antigen killing consumes both antigen and the effector; regulatory and treatment killing return their catalysts.","Raw day0 starts180days before treatment; full horizon2520days corresponds to clinical day−180..2340, including six months beyond the observed72month follow-up.","Two course-level marking jumps occur at raw days180/540. An additional what-if course occurs at1260; within-course daily administrations and infusion pharmacokinetics are not modeled.","The alternate forcing has a Gaussian input-rate envelope centered at raw1230days, width147days. Neither this center nor the integrated antigen maximum is asserted to match a clinical month30 peak.","CNS pools have no exit in the specified network. Their regularized ratio is an exploratory network proxy, not measured CNS damage or relapse probability.","The normalized immune denominator is positive in admitted contexts; a numerical zero extension does not define a new empty-system biological model.","No individual random effects, original clustering, calibration uncertainty, statistical likelihood or clinical optimization is reproduced."],"name":"Group 2 — common colored continuous configuration","outputs":[{"classification":"provisional","description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"classification":"provisional","description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"classification":"provisional","description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"classification":"provisional","description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"scenario_id":"msmp2","scientific_questions":["How do the model's key biological readouts change under group 2 — common colored continuous configuration?"],"time_span":{"end":2520,"start":0,"step":5}},{"controls":[],"description":"Declared continuous network context with formal model marking units and explicit pretreatment history.","interpretation_guardrails":["Continuous reconstruction with ordinary mass action x^m/m! and directly transcribed custom reaction rates; no stochastic distribution or fitted-patient replay.","State values are formal dimensionless model markings. Treatment is an abstract scaled marking, not mg, mol, concentration or receptor occupancy.","The colored configuration has self-Th17 passage kBBB*Th17^2/2 with net loss of one Th17 and entry of one CNS effector. Separate constitutive configurations add one to each pool at rate kBBB.","Both regulatory duplication transitions use peripheral Th1. Effector-antigen killing consumes both antigen and the effector; regulatory and treatment killing return their catalysts.","Raw day0 starts180days before treatment; full horizon2520days corresponds to clinical day−180..2340, including six months beyond the observed72month follow-up.","Two course-level marking jumps occur at raw days180/540. An additional what-if course occurs at1260; within-course daily administrations and infusion pharmacokinetics are not modeled.","The alternate forcing has a Gaussian input-rate envelope centered at raw1230days, width147days. Neither this center nor the integrated antigen maximum is asserted to match a clinical month30 peak.","CNS pools have no exit in the specified network. Their regularized ratio is an exploratory network proxy, not measured CNS damage or relapse probability.","The normalized immune denominator is positive in admitted contexts; a numerical zero extension does not define a new empty-system biological model.","No individual random effects, original clustering, calibration uncertainty, statistical likelihood or clinical optimization is reproduced."],"name":"Group 3 — common colored continuous configuration","outputs":[{"classification":"provisional","description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"classification":"provisional","description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"classification":"provisional","description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"classification":"provisional","description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"scenario_id":"msmp3","scientific_questions":["How do the model's key biological readouts change under group 3 — common colored continuous configuration?"],"time_span":{"end":2520,"start":0,"step":5}},{"controls":[],"description":"Declared continuous network context with formal model marking units and explicit pretreatment history.","interpretation_guardrails":["Continuous reconstruction with ordinary mass action x^m/m! and directly transcribed custom reaction rates; no stochastic distribution or fitted-patient replay.","State values are formal dimensionless model markings. Treatment is an abstract scaled marking, not mg, mol, concentration or receptor occupancy.","The colored configuration has self-Th17 passage kBBB*Th17^2/2 with net loss of one Th17 and entry of one CNS effector. Separate constitutive configurations add one to each pool at rate kBBB.","Both regulatory duplication transitions use peripheral Th1. Effector-antigen killing consumes both antigen and the effector; regulatory and treatment killing return their catalysts.","Raw day0 starts180days before treatment; full horizon2520days corresponds to clinical day−180..2340, including six months beyond the observed72month follow-up.","Two course-level marking jumps occur at raw days180/540. An additional what-if course occurs at1260; within-course daily administrations and infusion pharmacokinetics are not modeled.","The alternate forcing has a Gaussian input-rate envelope centered at raw1230days, width147days. Neither this center nor the integrated antigen maximum is asserted to match a clinical month30 peak.","CNS pools have no exit in the specified network. Their regularized ratio is an exploratory network proxy, not measured CNS damage or relapse probability.","The normalized immune denominator is positive in admitted contexts; a numerical zero extension does not define a new empty-system biological model.","No individual random effects, original clustering, calibration uncertainty, statistical likelihood or clinical optimization is reproduced."],"name":"Group2 — antigen pulse with two courses","outputs":[{"classification":"provisional","description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"classification":"provisional","description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"classification":"provisional","description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"classification":"provisional","description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"scenario_id":"msmp2-1","scientific_questions":["How do the model's key biological readouts change under group2 — antigen pulse with two courses?"],"time_span":{"end":2520,"start":0,"step":5}},{"controls":[],"description":"Declared continuous network context with formal model marking units and explicit pretreatment history.","interpretation_guardrails":["Continuous reconstruction with ordinary mass action x^m/m! and directly transcribed custom reaction rates; no stochastic distribution or fitted-patient replay.","State values are formal dimensionless model markings. Treatment is an abstract scaled marking, not mg, mol, concentration or receptor occupancy.","The colored configuration has self-Th17 passage kBBB*Th17^2/2 with net loss of one Th17 and entry of one CNS effector. Separate constitutive configurations add one to each pool at rate kBBB.","Both regulatory duplication transitions use peripheral Th1. Effector-antigen killing consumes both antigen and the effector; regulatory and treatment killing return their catalysts.","Raw day0 starts180days before treatment; full horizon2520days corresponds to clinical day−180..2340, including six months beyond the observed72month follow-up.","Two course-level marking jumps occur at raw days180/540. An additional what-if course occurs at1260; within-course daily administrations and infusion pharmacokinetics are not modeled.","The alternate forcing has a Gaussian input-rate envelope centered at raw1230days, width147days. Neither this center nor the integrated antigen maximum is asserted to match a clinical month30 peak.","CNS pools have no exit in the specified network. Their regularized ratio is an exploratory network proxy, not measured CNS damage or relapse probability.","The normalized immune denominator is positive in admitted contexts; a numerical zero extension does not define a new empty-system biological model.","No individual random effects, original clustering, calibration uncertainty, statistical likelihood or clinical optimization is reproduced."],"name":"Group2 — antigen pulse with three courses","outputs":[{"classification":"provisional","description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"classification":"provisional","description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"classification":"provisional","description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"classification":"provisional","description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"scenario_id":"msmp2-2","scientific_questions":["How do the model's key biological readouts change under group2 — antigen pulse with three courses?"],"time_span":{"end":2520,"start":0,"step":5}},{"controls":[],"description":"Declared continuous network context with formal model marking units and explicit pretreatment history.","interpretation_guardrails":["Continuous reconstruction with ordinary mass action x^m/m! and directly transcribed custom reaction rates; no stochastic distribution or fitted-patient replay.","State values are formal dimensionless model markings. Treatment is an abstract scaled marking, not mg, mol, concentration or receptor occupancy.","The colored configuration has self-Th17 passage kBBB*Th17^2/2 with net loss of one Th17 and entry of one CNS effector. Separate constitutive configurations add one to each pool at rate kBBB.","Both regulatory duplication transitions use peripheral Th1. Effector-antigen killing consumes both antigen and the effector; regulatory and treatment killing return their catalysts.","Raw day0 starts180days before treatment; full horizon2520days corresponds to clinical day−180..2340, including six months beyond the observed72month follow-up.","Two course-level marking jumps occur at raw days180/540. An additional what-if course occurs at1260; within-course daily administrations and infusion pharmacokinetics are not modeled.","The alternate forcing has a Gaussian input-rate envelope centered at raw1230days, width147days. Neither this center nor the integrated antigen maximum is asserted to match a clinical month30 peak.","CNS pools have no exit in the specified network. Their regularized ratio is an exploratory network proxy, not measured CNS damage or relapse probability.","The normalized immune denominator is positive in admitted contexts; a numerical zero extension does not define a new empty-system biological model.","No individual random effects, original clustering, calibration uncertainty, statistical likelihood or clinical optimization is reproduced."],"name":"Group1 — constitutive self process","outputs":[{"classification":"provisional","description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"classification":"provisional","description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"classification":"provisional","description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"classification":"provisional","description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"scenario_id":"group1-constitutive-self-configuration","scientific_questions":["How do the model's key biological readouts change under group1 — constitutive self process?"],"time_span":{"end":2520,"start":0,"step":5}},{"controls":[],"description":"Declared continuous network context with formal model marking units and explicit pretreatment history.","interpretation_guardrails":["Continuous reconstruction with ordinary mass action x^m/m! and directly transcribed custom reaction rates; no stochastic distribution or fitted-patient replay.","State values are formal dimensionless model markings. Treatment is an abstract scaled marking, not mg, mol, concentration or receptor occupancy.","The colored configuration has self-Th17 passage kBBB*Th17^2/2 with net loss of one Th17 and entry of one CNS effector. Separate constitutive configurations add one to each pool at rate kBBB.","Both regulatory duplication transitions use peripheral Th1. Effector-antigen killing consumes both antigen and the effector; regulatory and treatment killing return their catalysts.","Raw day0 starts180days before treatment; full horizon2520days corresponds to clinical day−180..2340, including six months beyond the observed72month follow-up.","Two course-level marking jumps occur at raw days180/540. An additional what-if course occurs at1260; within-course daily administrations and infusion pharmacokinetics are not modeled.","The alternate forcing has a Gaussian input-rate envelope centered at raw1230days, width147days. Neither this center nor the integrated antigen maximum is asserted to match a clinical month30 peak.","CNS pools have no exit in the specified network. Their regularized ratio is an exploratory network proxy, not measured CNS damage or relapse probability.","The normalized immune denominator is positive in admitted contexts; a numerical zero extension does not define a new empty-system biological model.","No individual random effects, original clustering, calibration uncertainty, statistical likelihood or clinical optimization is reproduced."],"name":"Group3 — constitutive self process","outputs":[{"classification":"provisional","description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"classification":"provisional","description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"classification":"provisional","description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"classification":"provisional","description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"scenario_id":"group3-constitutive-self-configuration","scientific_questions":["How do the model's key biological readouts change under group3 — constitutive self process?"],"time_span":{"end":2520,"start":0,"step":5}},{"controls":[],"description":"Declared continuous network context with formal model marking units and explicit pretreatment history.","interpretation_guardrails":["Continuous reconstruction with ordinary mass action x^m/m! and directly transcribed custom reaction rates; no stochastic distribution or fitted-patient replay.","State values are formal dimensionless model markings. Treatment is an abstract scaled marking, not mg, mol, concentration or receptor occupancy.","The colored configuration has self-Th17 passage kBBB*Th17^2/2 with net loss of one Th17 and entry of one CNS effector. Separate constitutive configurations add one to each pool at rate kBBB.","Both regulatory duplication transitions use peripheral Th1. Effector-antigen killing consumes both antigen and the effector; regulatory and treatment killing return their catalysts.","Raw day0 starts180days before treatment; full horizon2520days corresponds to clinical day−180..2340, including six months beyond the observed72month follow-up.","Two course-level marking jumps occur at raw days180/540. An additional what-if course occurs at1260; within-course daily administrations and infusion pharmacokinetics are not modeled.","The alternate forcing has a Gaussian input-rate envelope centered at raw1230days, width147days. Neither this center nor the integrated antigen maximum is asserted to match a clinical month30 peak.","CNS pools have no exit in the specified network. Their regularized ratio is an exploratory network proxy, not measured CNS damage or relapse probability.","The normalized immune denominator is positive in admitted contexts; a numerical zero extension does not define a new empty-system biological model.","No individual random effects, original clustering, calibration uncertainty, statistical likelihood or clinical optimization is reproduced."],"name":"Group2 — untreated network control","outputs":[{"classification":"provisional","description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"classification":"provisional","description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"classification":"provisional","description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"classification":"provisional","description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"scenario_id":"group2-untreated-network","scientific_questions":["How do the model's key biological readouts change under group2 — untreated network control?"],"time_span":{"end":2520,"start":0,"step":5}},{"controls":[],"description":"Declared continuous network context with formal model marking units and explicit pretreatment history.","interpretation_guardrails":["Continuous reconstruction with ordinary mass action x^m/m! and directly transcribed custom reaction rates; no stochastic distribution or fitted-patient replay.","State values are formal dimensionless model markings. Treatment is an abstract scaled marking, not mg, mol, concentration or receptor occupancy.","The colored configuration has self-Th17 passage kBBB*Th17^2/2 with net loss of one Th17 and entry of one CNS effector. Separate constitutive configurations add one to each pool at rate kBBB.","Both regulatory duplication transitions use peripheral Th1. Effector-antigen killing consumes both antigen and the effector; regulatory and treatment killing return their catalysts.","Raw day0 starts180days before treatment; full horizon2520days corresponds to clinical day−180..2340, including six months beyond the observed72month follow-up.","Two course-level marking jumps occur at raw days180/540. An additional what-if course occurs at1260; within-course daily administrations and infusion pharmacokinetics are not modeled.","The alternate forcing has a Gaussian input-rate envelope centered at raw1230days, width147days. Neither this center nor the integrated antigen maximum is asserted to match a clinical month30 peak.","CNS pools have no exit in the specified network. Their regularized ratio is an exploratory network proxy, not measured CNS damage or relapse probability.","The normalized immune denominator is positive in admitted contexts; a numerical zero extension does not define a new empty-system biological model.","No individual random effects, original clustering, calibration uncertainty, statistical likelihood or clinical optimization is reproduced."],"name":"Group3 — alternate fixed coefficient realization","outputs":[{"classification":"provisional","description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"classification":"provisional","description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"classification":"provisional","description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"classification":"provisional","description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"scenario_id":"group3-alternate-coefficients","scientific_questions":["How do the model's key biological readouts change under group3 — alternate fixed coefficient realization?"],"time_span":{"end":2520,"start":0,"step":5}},{"controls":[],"description":"Daily source-schedule resolution of the corresponding fixed continuous network context. This changes only the observation grid; it adds no biological condition, clinical claim or treatment mechanism.","interpretation_guardrails":["Continuous reconstruction with ordinary mass action x^m/m! and directly transcribed custom reaction rates; no stochastic distribution or fitted-patient replay.","State values are formal dimensionless model markings. Treatment is an abstract scaled marking, not mg, mol, concentration or receptor occupancy.","The colored configuration has self-Th17 passage kBBB*Th17^2/2 with net loss of one Th17 and entry of one CNS effector. Separate constitutive configurations add one to each pool at rate kBBB.","Both regulatory duplication transitions use peripheral Th1. Effector-antigen killing consumes both antigen and the effector; regulatory and treatment killing return their catalysts.","Raw day0 starts180days before treatment; full horizon2520days corresponds to clinical day−180..2340, including six months beyond the observed72month follow-up.","Two course-level marking jumps occur at raw days180/540. An additional what-if course occurs at1260; within-course daily administrations and infusion pharmacokinetics are not modeled.","The alternate forcing has a Gaussian input-rate envelope centered at raw1230days, width147days. Neither this center nor the integrated antigen maximum is asserted to match a clinical month30 peak.","CNS pools have no exit in the specified network. Their regularized ratio is an exploratory network proxy, not measured CNS damage or relapse probability.","The normalized immune denominator is positive in admitted contexts; a numerical zero extension does not define a new empty-system biological model.","No individual random effects, original clustering, calibration uncertainty, statistical likelihood or clinical optimization is reproduced."],"name":"Group 1 — common colored continuous configuration · daily source grid","outputs":[{"classification":"provisional","description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"classification":"provisional","description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"classification":"provisional","description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"classification":"provisional","description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"scenario_id":"msmp1-daily-source-grid","scientific_questions":["How do the model's key biological readouts change under group 1 — common colored continuous configuration · daily source grid?"],"time_span":{"end":2520,"start":0,"step":1}},{"controls":[],"description":"Daily source-schedule resolution of the corresponding fixed continuous network context. This changes only the observation grid; it adds no biological condition, clinical claim or treatment mechanism.","interpretation_guardrails":["Continuous reconstruction with ordinary mass action x^m/m! and directly transcribed custom reaction rates; no stochastic distribution or fitted-patient replay.","State values are formal dimensionless model markings. Treatment is an abstract scaled marking, not mg, mol, concentration or receptor occupancy.","The colored configuration has self-Th17 passage kBBB*Th17^2/2 with net loss of one Th17 and entry of one CNS effector. Separate constitutive configurations add one to each pool at rate kBBB.","Both regulatory duplication transitions use peripheral Th1. Effector-antigen killing consumes both antigen and the effector; regulatory and treatment killing return their catalysts.","Raw day0 starts180days before treatment; full horizon2520days corresponds to clinical day−180..2340, including six months beyond the observed72month follow-up.","Two course-level marking jumps occur at raw days180/540. An additional what-if course occurs at1260; within-course daily administrations and infusion pharmacokinetics are not modeled.","The alternate forcing has a Gaussian input-rate envelope centered at raw1230days, width147days. Neither this center nor the integrated antigen maximum is asserted to match a clinical month30 peak.","CNS pools have no exit in the specified network. Their regularized ratio is an exploratory network proxy, not measured CNS damage or relapse probability.","The normalized immune denominator is positive in admitted contexts; a numerical zero extension does not define a new empty-system biological model.","No individual random effects, original clustering, calibration uncertainty, statistical likelihood or clinical optimization is reproduced."],"name":"Group 2 — common colored continuous configuration · daily source grid","outputs":[{"classification":"provisional","description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"classification":"provisional","description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"classification":"provisional","description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"classification":"provisional","description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"scenario_id":"msmp2-daily-source-grid","scientific_questions":["How do the model's key biological readouts change under group 2 — common colored continuous configuration · daily source grid?"],"time_span":{"end":2520,"start":0,"step":1}},{"controls":[],"description":"Daily source-schedule resolution of the corresponding fixed continuous network context. This changes only the observation grid; it adds no biological condition, clinical claim or treatment mechanism.","interpretation_guardrails":["Continuous reconstruction with ordinary mass action x^m/m! and directly transcribed custom reaction rates; no stochastic distribution or fitted-patient replay.","State values are formal dimensionless model markings. Treatment is an abstract scaled marking, not mg, mol, concentration or receptor occupancy.","The colored configuration has self-Th17 passage kBBB*Th17^2/2 with net loss of one Th17 and entry of one CNS effector. Separate constitutive configurations add one to each pool at rate kBBB.","Both regulatory duplication transitions use peripheral Th1. Effector-antigen killing consumes both antigen and the effector; regulatory and treatment killing return their catalysts.","Raw day0 starts180days before treatment; full horizon2520days corresponds to clinical day−180..2340, including six months beyond the observed72month follow-up.","Two course-level marking jumps occur at raw days180/540. An additional what-if course occurs at1260; within-course daily administrations and infusion pharmacokinetics are not modeled.","The alternate forcing has a Gaussian input-rate envelope centered at raw1230days, width147days. Neither this center nor the integrated antigen maximum is asserted to match a clinical month30 peak.","CNS pools have no exit in the specified network. Their regularized ratio is an exploratory network proxy, not measured CNS damage or relapse probability.","The normalized immune denominator is positive in admitted contexts; a numerical zero extension does not define a new empty-system biological model.","No individual random effects, original clustering, calibration uncertainty, statistical likelihood or clinical optimization is reproduced."],"name":"Group 3 — common colored continuous configuration · daily source grid","outputs":[{"classification":"provisional","description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"classification":"provisional","description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"classification":"provisional","description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"classification":"provisional","description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"scenario_id":"msmp3-daily-source-grid","scientific_questions":["How do the model's key biological readouts change under group 3 — common colored continuous configuration · daily source grid?"],"time_span":{"end":2520,"start":0,"step":1}},{"controls":[],"description":"Daily source-schedule resolution of the corresponding fixed continuous network context. This changes only the observation grid; it adds no biological condition, clinical claim or treatment mechanism.","interpretation_guardrails":["Continuous reconstruction with ordinary mass action x^m/m! and directly transcribed custom reaction rates; no stochastic distribution or fitted-patient replay.","State values are formal dimensionless model markings. Treatment is an abstract scaled marking, not mg, mol, concentration or receptor occupancy.","The colored configuration has self-Th17 passage kBBB*Th17^2/2 with net loss of one Th17 and entry of one CNS effector. Separate constitutive configurations add one to each pool at rate kBBB.","Both regulatory duplication transitions use peripheral Th1. Effector-antigen killing consumes both antigen and the effector; regulatory and treatment killing return their catalysts.","Raw day0 starts180days before treatment; full horizon2520days corresponds to clinical day−180..2340, including six months beyond the observed72month follow-up.","Two course-level marking jumps occur at raw days180/540. An additional what-if course occurs at1260; within-course daily administrations and infusion pharmacokinetics are not modeled.","The alternate forcing has a Gaussian input-rate envelope centered at raw1230days, width147days. Neither this center nor the integrated antigen maximum is asserted to match a clinical month30 peak.","CNS pools have no exit in the specified network. Their regularized ratio is an exploratory network proxy, not measured CNS damage or relapse probability.","The normalized immune denominator is positive in admitted contexts; a numerical zero extension does not define a new empty-system biological model.","No individual random effects, original clustering, calibration uncertainty, statistical likelihood or clinical optimization is reproduced."],"name":"Group2 — antigen pulse with two courses · daily source grid","outputs":[{"classification":"provisional","description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"classification":"provisional","description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"classification":"provisional","description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"classification":"provisional","description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"scenario_id":"msmp2-1-daily-source-grid","scientific_questions":["How do the model's key biological readouts change under group2 — antigen pulse with two courses · daily source grid?"],"time_span":{"end":2520,"start":0,"step":1}},{"controls":[],"description":"Daily source-schedule resolution of the corresponding fixed continuous network context. This changes only the observation grid; it adds no biological condition, clinical claim or treatment mechanism.","interpretation_guardrails":["Continuous reconstruction with ordinary mass action x^m/m! and directly transcribed custom reaction rates; no stochastic distribution or fitted-patient replay.","State values are formal dimensionless model markings. Treatment is an abstract scaled marking, not mg, mol, concentration or receptor occupancy.","The colored configuration has self-Th17 passage kBBB*Th17^2/2 with net loss of one Th17 and entry of one CNS effector. Separate constitutive configurations add one to each pool at rate kBBB.","Both regulatory duplication transitions use peripheral Th1. Effector-antigen killing consumes both antigen and the effector; regulatory and treatment killing return their catalysts.","Raw day0 starts180days before treatment; full horizon2520days corresponds to clinical day−180..2340, including six months beyond the observed72month follow-up.","Two course-level marking jumps occur at raw days180/540. An additional what-if course occurs at1260; within-course daily administrations and infusion pharmacokinetics are not modeled.","The alternate forcing has a Gaussian input-rate envelope centered at raw1230days, width147days. Neither this center nor the integrated antigen maximum is asserted to match a clinical month30 peak.","CNS pools have no exit in the specified network. Their regularized ratio is an exploratory network proxy, not measured CNS damage or relapse probability.","The normalized immune denominator is positive in admitted contexts; a numerical zero extension does not define a new empty-system biological model.","No individual random effects, original clustering, calibration uncertainty, statistical likelihood or clinical optimization is reproduced."],"name":"Group2 — antigen pulse with three courses · daily source grid","outputs":[{"classification":"provisional","description":"TH1 over the selected simulation window.","key":"th1","label":"TH1","unit":"dimensionless"},{"classification":"provisional","description":"TH17 over the selected simulation window.","key":"th17","label":"TH17","unit":"dimensionless"},{"classification":"provisional","description":"Regulatory T-cell over the selected simulation window.","key":"treg","label":"Regulatory T-cell","unit":"dimensionless"},{"classification":"provisional","description":"Cns effector regulatory proxy over the selected simulation window.","key":"cns_effector_regulatory_proxy","label":"Cns effector regulatory proxy","unit":"dimensionless"}],"scenario_id":"msmp2-2-daily-source-grid","scientific_questions":["How do the model's key biological readouts change under group2 — antigen pulse with three courses · daily source grid?"],"time_span":{"end":2520,"start":0,"step":1}}],"targets":[{"key":"cd52","label":"CD52","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1016/j.jbi.2023.104546","locator":"Primary-reference pharmacological or study context; authored card and source-review context.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"therapeutics":[{"key":"alemtuzumab","label":"Alemtuzumab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.2.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"A coupled subcutaneous or intravenous PK/PD model linking mepolizumab absorption and distribution to concentration-dependent suppression and turnover of circulating eosinophils.","diseases":[{"key":"eosinophilic_asthma","label":"Eosinophilic asthma"}],"links":{"page":"/modeling/models/pouliquen-2015-mepolizumab-eosinophil-pkpd","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"Whole mAb","model_classes":["PKPD"],"model_id":"pouliquen_2015_mepolizumab_eosinophil_pkpd","name":"Mepolizumab exposure and blood eosinophils","outputs":[{"description":"Mepolizumab concentration over the selected simulation window.","key":"central_concentration_ng_mL","label":"Mepolizumab concentration","unit":null},{"description":"Blood eosinophil concentration over the selected simulation window.","key":"blood_eosinophils_GI_L","label":"Blood eosinophil concentration","unit":"Gcell/L"},{"description":"Eosinophil inhibition over the selected simulation window.","key":"eosinophil_inhibition_fraction","label":"Eosinophil inhibition","unit":null},{"description":"Exposure (AUC) over the selected simulation window.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"description":"Central-compartment drug amount over the selected simulation window.","key":"A_central_mg","label":"Central-compartment drug amount","unit":"mg"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[{"category":"model parameter","definition":"Clearance intravenous governing removal of modeled material from the relevant compartment.","description":"Clearance intravenous governing removal of modeled material from the relevant compartment.","key":"CL_iv_L_day","label":"Clearance intravenous","max":0.315,"min":0.105,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.001,"unit":"L/day","value":0.21},{"category":"model parameter","definition":"Central distribution volume intravenous used to convert modeled amount to concentration in the relevant compartment.","description":"Central distribution volume intravenous used to convert modeled amount to concentration in the relevant compartment.","key":"Vc_iv_L","label":"Central distribution volume intravenous","max":5.4,"min":1.8,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":0.01,"unit":"L","value":3.6},{"category":"model parameter","definition":"Absorption rate constant governing entry from the administration site.","description":"Absorption rate constant governing entry from the administration site.","key":"KA_1_day","label":"Absorption rate constant","max":0.29100000000000004,"min":0.097,"range_authority":"exploratory_from_released_default","review_status":"not asserted","source":"Released executable model definition; 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exact publication locator not reported","step":0.001,"unit":"dimensionless","value":0.928}],"description":"How do route and dose change mepolizumab exposure and the depth and duration of eosinophil suppression? 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The 30-minute reloading diagnostics are authored administration contexts; trial-specific and reloading durations are not fully identified.","Peripheral concentration is an apparent model coordinate. Loss states are accounting coordinates, not measured excretion. Continuous integrated AUC is not a population AUC over a dosing interval.","Changing the simulation start uses the supplied initial state at that time, without reconstructing earlier doses.","No original legacy population-modeling workflow fit, variability or residual likelihood, patient observations, prediction interval, population exposure summary or full paper-panel reproduction. Fitting and normal server scans are unavailable.","No subcutaneous formulation, biosimilar, explicit receptor binding, tumor response, missed-dose, washout or pregnancy recommendation."],"name":"Breast-cancer context: every three weeks","outputs":[{"classification":"provisional","description":"Central amount divided by the selected apparent central volume; mg/L equals micrograms/mL. Provisional fixed-effect exposure, not a source observation, individual estimate or clinical endpoint.","key":"concentration_mg_l","label":"Conditional central intravenous concentration","unit":"mg/L"}],"scenario_id":"BC_q3w","scientific_questions":["How does the conditional three-weekly exposure profile behave at fixed reference covariates?"],"time_span":{"end":6720,"start":0,"step":18.666666666666668}},{"controls":[],"description":"How does the conditional weekly exposure profile differ from three-weekly administration? 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The 30-minute reloading diagnostics are authored administration contexts; trial-specific and reloading durations are not fully identified.","Peripheral concentration is an apparent model coordinate. Loss states are accounting coordinates, not measured excretion. Continuous integrated AUC is not a population AUC over a dosing interval.","Changing the simulation start uses the supplied initial state at that time, without reconstructing earlier doses.","No original legacy population-modeling workflow fit, variability or residual likelihood, patient observations, prediction interval, population exposure summary or full paper-panel reproduction. Fitting and normal server scans are unavailable.","No subcutaneous formulation, biosimilar, explicit receptor binding, tumor response, missed-dose, washout or pregnancy recommendation."],"name":"Advanced-gastric-cancer context: every three weeks","outputs":[{"classification":"provisional","description":"Central amount divided by the selected apparent central volume; mg/L equals micrograms/mL. Provisional fixed-effect exposure, not a source observation, individual estimate or clinical endpoint.","key":"concentration_mg_l","label":"Conditional central intravenous concentration","unit":"mg/L"}],"scenario_id":"AGC_q3w","scientific_questions":["How do the gastric-cancer clearance and central-volume coefficients affect conditional exposure?"],"time_span":{"end":6720,"start":0,"step":18.666666666666668}},{"controls":[],"description":"How does the other-tumor clearance coefficient affect conditional exposure? 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The 30-minute reloading diagnostics are authored administration contexts; trial-specific and reloading durations are not fully identified.","Peripheral concentration is an apparent model coordinate. Loss states are accounting coordinates, not measured excretion. Continuous integrated AUC is not a population AUC over a dosing interval.","Changing the simulation start uses the supplied initial state at that time, without reconstructing earlier doses.","No original legacy population-modeling workflow fit, variability or residual likelihood, patient observations, prediction interval, population exposure summary or full paper-panel reproduction. 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Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 1 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-1-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 1 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 2 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-2-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 2 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 3 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-3-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 3 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 4 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-4-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 4 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 5 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-5-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 5 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 6 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-6-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 6 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 7 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-7-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 7 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 10 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-10-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 10 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 11 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-11-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 11 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 12 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-12-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 12 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 13 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-13-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 13 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 14 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-14-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 14 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 15 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-15-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 15 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 16 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-16-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 16 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 18 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"patient18-90mg-q8w-intensified-probe","scientific_questions":["How do the model's key biological readouts change under published parameter set 18 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. Original individual treatment histories are unavailable.","Published means already reflect their covariates; no additional body-weight scaling is applied.","F is converted from percent to fraction once, with administered depot and complementary non-systemic loss explicitly distinguished.","Parameter editing is held within each context because baseline changes require matching PASI initialization.","No posterior clone generation, response probability, successful personalized regimen, original patient-trajectory or clinical dosing claim is made."],"name":"Published parameter set 19 — exploratory 90 mg calendar","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"PASI score over the selected simulation window.","key":"pasi_score","label":"PASI score","unit":"dimensionless"},{"classification":"provisional","description":"PASI reduction fraction over the selected simulation window.","key":"pasi_reduction_fraction","label":"PASI reduction fraction","unit":"dimensionless"},{"classification":"provisional","description":"Nonfeedback clock or exposure readout.","key":"mean_central_concentration_mg_l","label":"Mean central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"parameter-set-19-90mg-prospective-calendar","scientific_questions":["How do the model's key biological readouts change under published parameter set 19 — exploratory 90 mg calendar?"],"time_span":{"end":616,"start":0,"step":1}},{"controls":[],"description":"Deterministic fixed-parameter exploration with explicitly authored administrations and initial conditions.","interpretation_guardrails":["Published individual conditional means define frozen parameter-set explorations; trajectories evaluated at these means generally differ from posterior-mean responses.","PK amounts start drug-free and PASI starts at the published predicted baseline. kin=kout times baseline is a declared drug-free-equilibrium closure.","The authored calendar uses90mg SC on days0,28,112 then every56days through560, with a predose endpoint at616days. 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They do not reconstruct earlier exposure or episodes.","C1-INH concentration increments have no therapeutic product/IU conversion. Full phase1b, nonadherence, hypothetical drug and stochastic source workflows remain pending."],"name":"First sampled virtual patient, 150 mg SC q2w lanadelumab","outputs":[{"classification":"provisional","description":"Conditional model quantity; source-state units and selected conditions apply.","key":"PK_Conc_Central_in_ugml","label":"Plasma lanadelumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Conditional model quantity; source-state units and selected conditions apply.","key":"bradykinin_pM","label":"Plasma bradykinin","unit":"pM"},{"classification":"provisional","description":"100 times free cleaved plasma HMWK divided by free cleaved plus free uncleaved plasma HMWK. HMWK-containing complexes are excluded. 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They do not reconstruct earlier exposure or episodes.","C1-INH concentration increments have no therapeutic product/IU conversion. Full phase1b, nonadherence, hypothetical drug and stochastic source workflows remain pending."],"name":"placebo","outputs":[{"classification":"provisional","description":"Conditional model quantity; source-state units and selected conditions apply.","key":"PK_Conc_Central_in_ugml","label":"Plasma lanadelumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Conditional model quantity; source-state units and selected conditions apply.","key":"bradykinin_pM","label":"Plasma bradykinin","unit":"pM"},{"classification":"provisional","description":"100 times free cleaved plasma HMWK divided by free cleaved plus free uncleaved plasma HMWK. HMWK-containing complexes are excluded. 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They do not reconstruct earlier exposure or episodes.","C1-INH concentration increments have no therapeutic product/IU conversion. Full phase1b, nonadherence, hypothetical drug and stochastic source workflows remain pending."],"name":"150mg q4w","outputs":[{"classification":"provisional","description":"Conditional model quantity; source-state units and selected conditions apply.","key":"PK_Conc_Central_in_ugml","label":"Plasma lanadelumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Conditional model quantity; source-state units and selected conditions apply.","key":"bradykinin_pM","label":"Plasma bradykinin","unit":"pM"},{"classification":"provisional","description":"100 times free cleaved plasma HMWK divided by free cleaved plus free uncleaved plasma HMWK. HMWK-containing complexes are excluded. 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The bounds span the selected HAE and healthy source settings.","key":"CS_ksyn_C1Inh","label":"C1-INH synthesis rate","max":39.608,"min":11.883,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":0.1,"unit":"nM/h","value":11.883},{"category":"conditional forcing","definition":"Amplitude control for the selected smooth attack-forcing profile. Paired conditions retain the same frozen pulse schedule; this control does not specify clinical attack counts or a newly sampled patient.","description":"Amplitude control for the selected smooth attack-forcing profile. Paired conditions retain the same frozen pulse schedule; this control does not specify clinical attack counts or a newly sampled patient.","key":"AA_AA_Fold_Max","label":"Attack-forcing amplitude","max":12,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":0.1,"unit":"dimensionless","value":12}],"description":"Explicit smooth12h source pulse;0.2 is a boundary diagnostic, not a draw from the open-lower-bound sampler.","interpretation_guardrails":["Conditional mechanistic simulations; no original population estimation, virtual cohort, uncertainty interval or clinical treatment recommendation.","The frozen locally regenerated SI-code sample (historical seed20260707) contains 47 smooth FXII-autoactivation pulses. Regimen comparisons reuse that same schedule and PK coordinates; they are paired conditional calculations, not trial reproduction.","Lanadelumab PK drives binding in the KKS one way. Nominal drug amount uses apparent V/F and CL/F; it is not a measured total-body antibody mass or a TMDD mass balance.","The 20pM bradykinin flag is instantaneous. Source episode counts require the original half-hour grid and >= threshold rule; the flag alone is not monthly attack frequency.","Source percentage outputs already include the factor100. Normalized cHMWK is percent of basal, equals100 at its source reference and may exceed100; it is not a probability.","PK parameter exploration domains are virtual-sampler truncations, not clinically validated marginal ranges. Healthy C1-INH synthesis and mean-weight typical PK are separate source conditions.","Observer integrals start at the selected simulation start. They do not reconstruct earlier exposure or episodes.","C1-INH concentration increments have no therapeutic product/IU conversion. Full phase1b, nonadherence, hypothetical drug and stochastic source workflows remain pending."],"name":"Single smooth attack, severity 1.0","outputs":[{"classification":"provisional","description":"Conditional model quantity; source-state units and selected conditions apply.","key":"PK_Conc_Central_in_ugml","label":"Plasma lanadelumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Conditional model quantity; source-state units and selected conditions apply.","key":"bradykinin_pM","label":"Plasma bradykinin","unit":"pM"},{"classification":"provisional","description":"100 times free cleaved plasma HMWK divided by free cleaved plus free uncleaved plasma HMWK. HMWK-containing complexes are excluded. The equation already gives a percentage; displayed values are not rescaled.","key":"CS_prct_HK2Chain","label":"Cleaved hmwk numerical percent","unit":"%"}],"scenario_id":"single_smooth_attack_1p0","scientific_questions":["How do the model's key biological readouts change under single smooth attack, severity 1.0?"],"time_span":{"end":1048,"start":0,"step":0.5}},{"controls":[{"category":"pharmacokinetics","definition":"Apparent central volume after subcutaneous administration, in L. It divides absorbed input and apparent clearance in the concentration equation. The exploratory bounds are the pinned source virtual-patient sampling domain, not a clinical dose recommendation.","description":"Apparent central volume after subcutaneous administration, in L. It divides absorbed input and apparent clearance in the concentration equation. The exploratory bounds are the pinned source virtual-patient sampling domain, not a clinical dose recommendation.","key":"PK_V_F","label":"Apparent volume (V/F)","max":32.7,"min":7.52,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":0.01,"unit":"L","value":8.056385572112207},{"category":"pharmacokinetics","definition":"Apparent clearance after subcutaneous administration, in L/h. Central loss is (CL/F)/(V/F) times plasma lanadelumab concentration. The exploratory bounds retain the source virtual-patient sampling domain.","description":"Apparent clearance after subcutaneous administration, in L/h. Central loss is (CL/F)/(V/F) times plasma lanadelumab concentration. The exploratory bounds retain the source virtual-patient sampling domain.","key":"PK_CL_F","label":"Apparent clearance (CL/F)","max":0.0879,"min":0.0123,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":9.999999999999999e-05,"unit":"L/h","value":0.014006655808911094},{"category":"pharmacokinetics","definition":"First-order absorption rate from the subcutaneous depot, in 1/h. Absorbed depot amount enters the apparent central concentration equation. The exploratory bounds retain the source virtual-patient sampling domain.","description":"First-order absorption rate from the subcutaneous depot, in 1/h. Absorbed depot amount enters the apparent central concentration equation. The exploratory bounds retain the source virtual-patient sampling domain.","key":"PK_ka","label":"Subcutaneous absorption rate","max":0.0395,"min":0.00613,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":9.999999999999999e-05,"unit":"1/h","value":0.0179},{"category":"contact-system regulation","definition":"Constant plasma C1 inhibitor synthesis input, in nM/h. Changing synthesis does not reset the independently specified initial C1-INH concentration. The bounds span the selected HAE and healthy source settings.","description":"Constant plasma C1 inhibitor synthesis input, in nM/h. Changing synthesis does not reset the independently specified initial C1-INH concentration. The bounds span the selected HAE and healthy source settings.","key":"CS_ksyn_C1Inh","label":"C1-INH synthesis rate","max":39.608,"min":11.883,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":0.1,"unit":"nM/h","value":11.883},{"category":"conditional forcing","definition":"Amplitude control for the selected smooth attack-forcing profile. Paired conditions retain the same frozen pulse schedule; this control does not specify clinical attack counts or a newly sampled patient.","description":"Amplitude control for the selected smooth attack-forcing profile. 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Regimen comparisons reuse that same schedule and PK coordinates; they are paired conditional calculations, not trial reproduction.","Lanadelumab PK drives binding in the KKS one way. Nominal drug amount uses apparent V/F and CL/F; it is not a measured total-body antibody mass or a TMDD mass balance.","The 20pM bradykinin flag is instantaneous. Source episode counts require the original half-hour grid and >= threshold rule; the flag alone is not monthly attack frequency.","Source percentage outputs already include the factor100. Normalized cHMWK is percent of basal, equals100 at its source reference and may exceed100; it is not a probability.","PK parameter exploration domains are virtual-sampler truncations, not clinically validated marginal ranges. Healthy C1-INH synthesis and mean-weight typical PK are separate source conditions.","Observer integrals start at the selected simulation start. They do not reconstruct earlier exposure or episodes.","C1-INH concentration increments have no therapeutic product/IU conversion. Full phase1b, nonadherence, hypothetical drug and stochastic source workflows remain pending."],"name":"300mg SC, typical PK at 36.7kg","outputs":[{"classification":"provisional","description":"Conditional model quantity; source-state units and selected conditions apply.","key":"PK_Conc_Central_in_ugml","label":"Plasma lanadelumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Conditional model quantity; source-state units and selected conditions apply.","key":"bradykinin_pM","label":"Plasma bradykinin","unit":"pM"},{"classification":"provisional","description":"100 times free cleaved plasma HMWK divided by free cleaved plus free uncleaved plasma HMWK. HMWK-containing complexes are excluded. The equation already gives a percentage; displayed values are not rescaled.","key":"CS_prct_HK2Chain","label":"Cleaved hmwk numerical percent","unit":"%"}],"scenario_id":"single300_typical_wt36p7","scientific_questions":["How do the model's key biological readouts change under 300mg sc, typical pk at 36.7kg?"],"time_span":{"end":4000,"start":0,"step":6}},{"controls":[{"category":"pharmacokinetics","definition":"Apparent central volume after subcutaneous administration, in L. It divides absorbed input and apparent clearance in the concentration equation. The exploratory bounds are the pinned source virtual-patient sampling domain, not a clinical dose recommendation.","description":"Apparent central volume after subcutaneous administration, in L. It divides absorbed input and apparent clearance in the concentration equation. The exploratory bounds are the pinned source virtual-patient sampling domain, not a clinical dose recommendation.","key":"PK_V_F","label":"Apparent volume (V/F)","max":32.7,"min":7.52,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":0.1,"unit":"L","value":14.224684002073936},{"category":"pharmacokinetics","definition":"Apparent clearance after subcutaneous administration, in L/h. Central loss is (CL/F)/(V/F) times plasma lanadelumab concentration. The exploratory bounds retain the source virtual-patient sampling domain.","description":"Apparent clearance after subcutaneous administration, in L/h. Central loss is (CL/F)/(V/F) times plasma lanadelumab concentration. The exploratory bounds retain the source virtual-patient sampling domain.","key":"PK_CL_F","label":"Apparent clearance (CL/F)","max":0.0879,"min":0.0123,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":9.999999999999999e-05,"unit":"L/h","value":0.028389292833182707},{"category":"pharmacokinetics","definition":"First-order absorption rate from the subcutaneous depot, in 1/h. Absorbed depot amount enters the apparent central concentration equation. The exploratory bounds retain the source virtual-patient sampling domain.","description":"First-order absorption rate from the subcutaneous depot, in 1/h. Absorbed depot amount enters the apparent central concentration equation. The exploratory bounds retain the source virtual-patient sampling domain.","key":"PK_ka","label":"Subcutaneous absorption rate","max":0.0395,"min":0.00613,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":9.999999999999999e-05,"unit":"1/h","value":0.0179},{"category":"contact-system regulation","definition":"Constant plasma C1 inhibitor synthesis input, in nM/h. Changing synthesis does not reset the independently specified initial C1-INH concentration. The bounds span the selected HAE and healthy source settings.","description":"Constant plasma C1 inhibitor synthesis input, in nM/h. Changing synthesis does not reset the independently specified initial C1-INH concentration. The bounds span the selected HAE and healthy source settings.","key":"CS_ksyn_C1Inh","label":"C1-INH synthesis rate","max":39.608,"min":11.883,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":0.1,"unit":"nM/h","value":11.883},{"category":"conditional forcing","definition":"Amplitude control for the selected smooth attack-forcing profile. Paired conditions retain the same frozen pulse schedule; this control does not specify clinical attack counts or a newly sampled patient.","description":"Amplitude control for the selected smooth attack-forcing profile. Paired conditions retain the same frozen pulse schedule; this control does not specify clinical attack counts or a newly sampled patient.","key":"AA_AA_Fold_Max","label":"Attack-forcing amplitude","max":12,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":0.12,"unit":"dimensionless","value":0}],"description":"Zero-eta source weight allometry, unrounded fixed effects. Weight is a preset reference; not clinical validation or a sampled patient.","interpretation_guardrails":["Conditional mechanistic simulations; no original population estimation, virtual cohort, uncertainty interval or clinical treatment recommendation.","The frozen locally regenerated SI-code sample (historical seed20260707) contains 47 smooth FXII-autoactivation pulses. Regimen comparisons reuse that same schedule and PK coordinates; they are paired conditional calculations, not trial reproduction.","Lanadelumab PK drives binding in the KKS one way. Nominal drug amount uses apparent V/F and CL/F; it is not a measured total-body antibody mass or a TMDD mass balance.","The 20pM bradykinin flag is instantaneous. Source episode counts require the original half-hour grid and >= threshold rule; the flag alone is not monthly attack frequency.","Source percentage outputs already include the factor100. Normalized cHMWK is percent of basal, equals100 at its source reference and may exceed100; it is not a probability.","PK parameter exploration domains are virtual-sampler truncations, not clinically validated marginal ranges. Healthy C1-INH synthesis and mean-weight typical PK are separate source conditions.","Observer integrals start at the selected simulation start. They do not reconstruct earlier exposure or episodes.","C1-INH concentration increments have no therapeutic product/IU conversion. Full phase1b, nonadherence, hypothetical drug and stochastic source workflows remain pending."],"name":"300mg SC, typical PK at 81.1kg","outputs":[{"classification":"provisional","description":"Conditional model quantity; source-state units and selected conditions apply.","key":"PK_Conc_Central_in_ugml","label":"Plasma lanadelumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Conditional model quantity; source-state units and selected conditions apply.","key":"bradykinin_pM","label":"Plasma bradykinin","unit":"pM"},{"classification":"provisional","description":"100 times free cleaved plasma HMWK divided by free cleaved plus free uncleaved plasma HMWK. HMWK-containing complexes are excluded. The equation already gives a percentage; displayed values are not rescaled.","key":"CS_prct_HK2Chain","label":"Cleaved hmwk numerical percent","unit":"%"}],"scenario_id":"single300_typical_wt81p1","scientific_questions":["How do the model's key biological readouts change under 300mg sc, typical pk at 81.1kg?"],"time_span":{"end":4000,"start":0,"step":6}},{"controls":[{"category":"pharmacokinetics","definition":"Apparent central volume after subcutaneous administration, in L. It divides absorbed input and apparent clearance in the concentration equation. The exploratory bounds are the pinned source virtual-patient sampling domain, not a clinical dose recommendation.","description":"Apparent central volume after subcutaneous administration, in L. It divides absorbed input and apparent clearance in the concentration equation. The exploratory bounds are the pinned source virtual-patient sampling domain, not a clinical dose recommendation.","key":"PK_V_F","label":"Apparent volume (V/F)","max":32.7,"min":7.52,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":0.1,"unit":"L","value":24.993427440807277},{"category":"pharmacokinetics","definition":"Apparent clearance after subcutaneous administration, in L/h. Central loss is (CL/F)/(V/F) times plasma lanadelumab concentration. The exploratory bounds retain the source virtual-patient sampling domain.","description":"Apparent clearance after subcutaneous administration, in L/h. Central loss is (CL/F)/(V/F) times plasma lanadelumab concentration. The exploratory bounds retain the source virtual-patient sampling domain.","key":"PK_CL_F","label":"Apparent clearance (CL/F)","max":0.0879,"min":0.0123,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":9.999999999999999e-05,"unit":"L/h","value":0.05719278111367462},{"category":"pharmacokinetics","definition":"First-order absorption rate from the subcutaneous depot, in 1/h. Absorbed depot amount enters the apparent central concentration equation. The exploratory bounds retain the source virtual-patient sampling domain.","description":"First-order absorption rate from the subcutaneous depot, in 1/h. Absorbed depot amount enters the apparent central concentration equation. The exploratory bounds retain the source virtual-patient sampling domain.","key":"PK_ka","label":"Subcutaneous absorption rate","max":0.0395,"min":0.00613,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":9.999999999999999e-05,"unit":"1/h","value":0.0179},{"category":"contact-system regulation","definition":"Constant plasma C1 inhibitor synthesis input, in nM/h. Changing synthesis does not reset the independently specified initial C1-INH concentration. The bounds span the selected HAE and healthy source settings.","description":"Constant plasma C1 inhibitor synthesis input, in nM/h. Changing synthesis does not reset the independently specified initial C1-INH concentration. The bounds span the selected HAE and healthy source settings.","key":"CS_ksyn_C1Inh","label":"C1-INH synthesis rate","max":39.608,"min":11.883,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":0.1,"unit":"nM/h","value":11.883},{"category":"conditional forcing","definition":"Amplitude control for the selected smooth attack-forcing profile. Paired conditions retain the same frozen pulse schedule; this control does not specify clinical attack counts or a newly sampled patient.","description":"Amplitude control for the selected smooth attack-forcing profile. Paired conditions retain the same frozen pulse schedule; this control does not specify clinical attack counts or a newly sampled patient.","key":"AA_AA_Fold_Max","label":"Attack-forcing amplitude","max":12,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Conditional source exploration domain","step":0.12,"unit":"dimensionless","value":0}],"description":"Zero-eta source weight allometry, unrounded fixed effects. Weight is a preset reference; not clinical validation or a sampled patient.","interpretation_guardrails":["Conditional mechanistic simulations; no original population estimation, virtual cohort, uncertainty interval or clinical treatment recommendation.","The frozen locally regenerated SI-code sample (historical seed20260707) contains 47 smooth FXII-autoactivation pulses. Regimen comparisons reuse that same schedule and PK coordinates; they are paired conditional calculations, not trial reproduction.","Lanadelumab PK drives binding in the KKS one way. Nominal drug amount uses apparent V/F and CL/F; it is not a measured total-body antibody mass or a TMDD mass balance.","The 20pM bradykinin flag is instantaneous. Source episode counts require the original half-hour grid and >= threshold rule; the flag alone is not monthly attack frequency.","Source percentage outputs already include the factor100. Normalized cHMWK is percent of basal, equals100 at its source reference and may exceed100; it is not a probability.","PK parameter exploration domains are virtual-sampler truncations, not clinically validated marginal ranges. Healthy C1-INH synthesis and mean-weight typical PK are separate source conditions.","Observer integrals start at the selected simulation start. They do not reconstruct earlier exposure or episodes.","C1-INH concentration increments have no therapeutic product/IU conversion. Full phase1b, nonadherence, hypothetical drug and stochastic source workflows remain pending."],"name":"300mg SC, typical PK at 178.0kg","outputs":[{"classification":"provisional","description":"Conditional model quantity; source-state units and selected conditions apply.","key":"PK_Conc_Central_in_ugml","label":"Plasma lanadelumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Conditional model quantity; source-state units and selected conditions apply.","key":"bradykinin_pM","label":"Plasma bradykinin","unit":"pM"},{"classification":"provisional","description":"100 times free cleaved plasma HMWK divided by free cleaved plus free uncleaved plasma HMWK. HMWK-containing complexes are excluded. The equation already gives a percentage; displayed values are not rescaled.","key":"CS_prct_HK2Chain","label":"Cleaved hmwk numerical percent","unit":"%"}],"scenario_id":"single300_typical_wt178p0","scientific_questions":["How do the model's key biological readouts change under 300mg sc, typical pk at 178.0kg?"],"time_span":{"end":4000,"start":0,"step":6}}],"targets":[{"key":"plasma_kallikrein","label":"Plasma kallikrein"}],"therapeutics":[{"key":"lanadelumab","label":"Lanadelumab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.3.0"},{"availability":{"catalog_qualified":true,"released":true},"description":"Two-compartment IV atezolizumab exposure with fixed weight, albumin, tumor-burden and ADA effects. Explicit finite infusions and cohort-specific source domains support conditional exploration.","diseases":[{"key":"pediatric_and_young_adult_malignancies","label":"Pediatric and young-adult malignancies"}],"links":{"page":"/modeling/models/shemesh-2019-atezolizumab-pediatric-poppk-safety","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"Whole mAb","model_classes":["two-compartment IV PK","fixed covariate effects"],"model_id":"shemesh_2019_atezolizumab_pediatric_poppk_safety","name":"Atezolizumab exposure across pediatric and young-adult cohorts","outputs":[{"description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":9.5,"min":8.7,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.01,"unit":"kg","value":9.1},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":35,"min":30,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":33},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":83,"min":35,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"mm","value":59},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":0}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"Infant median covariates","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"infant_lt2_15mgkg_q3w_figure2_source_limited","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":74.4,"min":12,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"kg","value":22.5},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":46,"min":23,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":41},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":301,"min":15,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"mm","value":55},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":0}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"Child median covariates","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"child_lt30kg_15mgkg_q3w_source_limited","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":105,"min":28.2,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"kg","value":51.1},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":49,"min":29,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":41},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":208,"min":11,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"mm","value":78},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":0}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"Adolescent median covariates","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"adolescent_ge45kg_15mgkg_q3w_source_limited","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":154,"min":46.2,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"kg","value":61},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":47,"min":27,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":39},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":258,"min":10,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":1,"unit":"mm","value":120},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":0}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"Young-adult median covariates","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"young_adult_57to65kg_1200mg_q3w_source_limited","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":105,"min":28.2,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"kg","value":79.9},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":49,"min":29,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":41},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":208,"min":11,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"mm","value":78},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":0}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"Just below pediatric dose cap","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"source_review_below_cap","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":105,"min":28.2,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"kg","value":80},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":49,"min":29,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":41},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":208,"min":11,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"mm","value":78},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":0}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"At pediatric dose cap","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"source_review_at_cap","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":105,"min":28.2,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":1,"unit":"kg","value":105},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":49,"min":29,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":41},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":208,"min":11,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"mm","value":78},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":0}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"105kg adolescent with capped dose","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"source_review_high_weight_pediatric","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":9.5,"min":8.7,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.01,"unit":"kg","value":8.7},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":35,"min":30,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":33},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":83,"min":35,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"mm","value":59},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":0}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"8.7kg infant boundary","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"source_review_infant_low_weight","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":154,"min":46.2,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":1,"unit":"kg","value":154},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":47,"min":27,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":39},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":258,"min":10,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":1,"unit":"mm","value":120},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":0}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"154kg young-adult boundary","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"source_review_high_weight_young_adult","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":74.4,"min":12,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"kg","value":22.5},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":46,"min":23,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":41},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":301,"min":15,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"mm","value":55},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":1}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"Child with positive ADA status","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"source_review_child_ada_positive","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":154,"min":46.2,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"kg","value":61},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":47,"min":27,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":39},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":258,"min":10,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":1,"unit":"mm","value":120},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":1}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"Young adult with positive ADA status","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"source_review_young_adult_ada_positive","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":74.4,"min":12,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"kg","value":22.5},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":46,"min":23,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":23},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":301,"min":15,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"mm","value":55},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":0}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"Low albumin covariate","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"source_review_low_albumin","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":105,"min":28.2,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"kg","value":51.1},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":49,"min":29,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":49},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":208,"min":11,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"mm","value":78},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":0}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"High albumin covariate","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"source_review_high_albumin","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":105,"min":28.2,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"kg","value":51.1},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":49,"min":29,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":41},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":208,"min":11,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"mm","value":11},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":0}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"Low tumor burden covariate","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"source_review_low_tumor_burden","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":74.4,"min":12,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"kg","value":22.5},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":46,"min":23,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":41},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":301,"min":15,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":1,"unit":"mm","value":301},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":0}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"High tumor burden covariate","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"source_review_high_tumor_burden","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}},{"controls":[{"category":"Covariate","definition":"Body weight used for body-size scaling in the model.","description":"Body weight used for body-size scaling in the model.","key":"body_weight_kg","label":"Body weight","max":105,"min":28.2,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"kg","value":77},{"category":"Covariate","definition":"Albumin coefficient used by the released system of model equations.","description":"Albumin coefficient used by the released system of model equations.","key":"albumin_g_L","label":"Albumin","max":49,"min":29,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"g/L","value":40},{"category":"Covariate","definition":"Tumor burden coefficient used by the released system of model equations.","description":"Tumor burden coefficient used by the released system of model equations.","key":"tumor_burden_mm","label":"Tumor burden","max":208,"min":11,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Observed marginal covariate range for the selected source cohort; joint combinations are not population validation.","step":0.1,"unit":"mm","value":63},{"category":"Covariate","definition":"Ada positive indicator coefficient used by the released system of model equations.","description":"Ada positive indicator coefficient used by the released system of model equations.","key":"ada_positive","label":"Ada positive indicator","max":1,"min":0,"range_authority":"released_parameter_bounds","review_status":"not asserted","source":"Released executable model definition; exact publication locator not reported","step":1,"unit":"dimensionless","value":0}],"description":"Conditional source fixed-effect preset. Dose amounts are fixed by default; select Recalculate paper regimen to couple weight and dose.","interpretation_guardrails":["Conditional fixed-effect exposure only: no original population fit, prediction interval, efficacy, safety or clinical dosing recommendation.","Age cohort selects observed covariate bounds and the paper dose rule. Age is not a covariate in the final PK equations; there is no neonatal or maturation model.","The infant cohort contains only two participants; the youngest observed participant was seven months old. Marginal covariate ranges do not reconstruct joint patient records.","Keep selected dose retains absolute mg after covariate edits. Recalculate paper regimen changes every infusion to min(15 mg/kg, 1200 mg) in pediatric cohorts or flat 1200 mg in young adults.","First infusion 60 minutes, later infusions 30 minutes, every 21 days for 10 doses. Timing is retained in both dosing modes.","The 6 ug/mL benchmark was preclinical-derived. Its instantaneous indicator is not efficacy, cycle trough or population target-attainment probability.","Continuous AUC integrates central concentration from the selected simulation start. Changing the start applies the supplied initial state there without reconstructing earlier exposure.","No original random effects, residual likelihood, population exposure distribution or full paper-panel reproduction is asserted. Fitting and normal server scans remain unavailable."],"name":"Reference covariates","outputs":[{"classification":"provisional","description":"Central amount divided by covariate-adjusted central volume; mg/L and ug/mL have equal numerical values.","key":"C_central_ug_mL","label":"Central atezolizumab concentration","unit":"ug/mL"},{"classification":"provisional","description":"Continuous integral of central concentration from the selected simulation start, using the supplied initial state.","key":"AUC_ug_day_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Fixed-effect clearance scaled by weight, albumin, tumor burden and anti-drug-antibody status.","key":"CL_L_day","label":"Systemic clearance","unit":"L/day"},{"classification":"provisional","description":"Central volume scaled by weight and albumin; age cohort is context rather than an age covariate.","key":"V1_L","label":"Central distribution volume","unit":"L"}],"scenario_id":"source_review_reference_covariates","scientific_questions":["How do the selected cohort covariates and explicitly chosen dose policy change central exposure?"],"time_span":{"end":210,"start":0,"step":0.25}}],"targets":[{"key":"pdl1","label":"PD-L1 / CD274"}],"therapeutics":[{"key":"atezolizumab","label":"Atezolizumab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.2.4"},{"availability":{"catalog_qualified":true,"released":true},"description":"Explore concentration decay from specified initial concentrations and constant loss rates. Published cycle-one exposure summaries are shown separately as reference data.","diseases":[{"key":"relapsed_or_refractory_b_cell_non_hodgkin_lymphoma","label":"Relapsed or refractory B-cell non-Hodgkin lymphoma","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s10637-018-0570-4","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"links":{"page":"/modeling/models/stathis-2018-imgn529-cd37-adc-phase1-nca","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"Antibody-drug conjugate","model_classes":["Authored conditional exponential concentration decay","Read-only aggregate NCA reference","Exposure diagnostics"],"model_id":"stathis_2018_imgn529_cd37_adc_phase1_nca","name":"IMGN529 exposure: concentration decay and NCA references","outputs":[{"description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"plasma_imgn529_ug_mL","label":"Conditional plasma concentration","unit":"ug/mL"},{"description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"auc_h_ug_mL","label":"Exposure (AUC)","unit":"h*ug/mL"},{"description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"modeled_remaining_auc_h_ug_mL","label":"Modeled remaining AUC","unit":"h*ug/mL"},{"description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"assay_quantitation_ratio","label":"Assay quantitation ratio","unit":"dimensionless"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Authored conditional exponential concentration decay from a specified initial concentration and fixed rate; not original patient PK, NCA recomputation or a structural TMDD fit.","interpretation_guardrails":["Authored conditional concentration decay; no original individual PK, noncompartmental recomputation, population fit or clinical endpoint prediction.","Initial concentration is supplied by the selected preset. Nominal mg/kg dose is a context label, not an administered event or identified body-mass assignment.","The dose-curve coefficients are fixed authored interpolation inputs. Their legacy symbols do not establish mechanistic target-mediated clearance.","Concentration loss and C+loss=C0 use ug/mL, not eliminated drug mass. No source cohort-mean volume/clearance is assigned as a structural compartment.","Exposure and quantitation calculations follow the declared conditional backbone, including mathematical continuation below assay quantitation.","NCA mean/SD references are aggregate observations; absent SD cells are not zero variability and no population intervals are generated."],"name":"Reported-summary initialization, 0.1 mg/kg context","outputs":[{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"plasma_imgn529_ug_mL","label":"Conditional plasma concentration","unit":"ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"auc_h_ug_mL","label":"Exposure (AUC)","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"modeled_remaining_auc_h_ug_mL","label":"Modeled remaining AUC","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"assay_quantitation_ratio","label":"Assay quantitation ratio","unit":"dimensionless"}],"scenario_id":"stathis_dose_0p1_exponential_probe","scientific_questions":["How do the model's key biological readouts change under reported-summary initialization, 0.1 mg/kg context?"],"time_span":{"end":504,"start":0,"step":2}},{"controls":[],"description":"Authored conditional exponential concentration decay from a specified initial concentration and fixed rate; not original patient PK, NCA recomputation or a structural TMDD fit.","interpretation_guardrails":["Authored conditional concentration decay; no original individual PK, noncompartmental recomputation, population fit or clinical endpoint prediction.","Initial concentration is supplied by the selected preset. Nominal mg/kg dose is a context label, not an administered event or identified body-mass assignment.","The dose-curve coefficients are fixed authored interpolation inputs. Their legacy symbols do not establish mechanistic target-mediated clearance.","Concentration loss and C+loss=C0 use ug/mL, not eliminated drug mass. No source cohort-mean volume/clearance is assigned as a structural compartment.","Exposure and quantitation calculations follow the declared conditional backbone, including mathematical continuation below assay quantitation.","NCA mean/SD references are aggregate observations; absent SD cells are not zero variability and no population intervals are generated."],"name":"Reported-summary initialization, 0.2 mg/kg context","outputs":[{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"plasma_imgn529_ug_mL","label":"Conditional plasma concentration","unit":"ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"auc_h_ug_mL","label":"Exposure (AUC)","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"modeled_remaining_auc_h_ug_mL","label":"Modeled remaining AUC","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"assay_quantitation_ratio","label":"Assay quantitation ratio","unit":"dimensionless"}],"scenario_id":"stathis_dose_0p2_exponential_probe","scientific_questions":["How do the model's key biological readouts change under reported-summary initialization, 0.2 mg/kg context?"],"time_span":{"end":504,"start":0,"step":2}},{"controls":[],"description":"Authored conditional exponential concentration decay from a specified initial concentration and fixed rate; not original patient PK, NCA recomputation or a structural TMDD fit.","interpretation_guardrails":["Authored conditional concentration decay; no original individual PK, noncompartmental recomputation, population fit or clinical endpoint prediction.","Initial concentration is supplied by the selected preset. Nominal mg/kg dose is a context label, not an administered event or identified body-mass assignment.","The dose-curve coefficients are fixed authored interpolation inputs. Their legacy symbols do not establish mechanistic target-mediated clearance.","Concentration loss and C+loss=C0 use ug/mL, not eliminated drug mass. No source cohort-mean volume/clearance is assigned as a structural compartment.","Exposure and quantitation calculations follow the declared conditional backbone, including mathematical continuation below assay quantitation.","NCA mean/SD references are aggregate observations; absent SD cells are not zero variability and no population intervals are generated."],"name":"Reported-summary initialization, 0.4 mg/kg context","outputs":[{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"plasma_imgn529_ug_mL","label":"Conditional plasma concentration","unit":"ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"auc_h_ug_mL","label":"Exposure (AUC)","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"modeled_remaining_auc_h_ug_mL","label":"Modeled remaining AUC","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"assay_quantitation_ratio","label":"Assay quantitation ratio","unit":"dimensionless"}],"scenario_id":"stathis_dose_0p4_exponential_probe","scientific_questions":["How do the model's key biological readouts change under reported-summary initialization, 0.4 mg/kg context?"],"time_span":{"end":504,"start":0,"step":2}},{"controls":[],"description":"Authored conditional exponential concentration decay from a specified initial concentration and fixed rate; not original patient PK, NCA recomputation or a structural TMDD fit.","interpretation_guardrails":["Authored conditional concentration decay; no original individual PK, noncompartmental recomputation, population fit or clinical endpoint prediction.","Initial concentration is supplied by the selected preset. Nominal mg/kg dose is a context label, not an administered event or identified body-mass assignment.","The dose-curve coefficients are fixed authored interpolation inputs. Their legacy symbols do not establish mechanistic target-mediated clearance.","Concentration loss and C+loss=C0 use ug/mL, not eliminated drug mass. No source cohort-mean volume/clearance is assigned as a structural compartment.","Exposure and quantitation calculations follow the declared conditional backbone, including mathematical continuation below assay quantitation.","NCA mean/SD references are aggregate observations; absent SD cells are not zero variability and no population intervals are generated."],"name":"Reported-summary initialization, 0.7 mg/kg context","outputs":[{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"plasma_imgn529_ug_mL","label":"Conditional plasma concentration","unit":"ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"auc_h_ug_mL","label":"Exposure (AUC)","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"modeled_remaining_auc_h_ug_mL","label":"Modeled remaining AUC","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"assay_quantitation_ratio","label":"Assay quantitation ratio","unit":"dimensionless"}],"scenario_id":"stathis_dose_0p7_exponential_probe","scientific_questions":["How do the model's key biological readouts change under reported-summary initialization, 0.7 mg/kg context?"],"time_span":{"end":504,"start":0,"step":2}},{"controls":[],"description":"Authored conditional exponential concentration decay from a specified initial concentration and fixed rate; not original patient PK, NCA recomputation or a structural TMDD fit.","interpretation_guardrails":["Authored conditional concentration decay; no original individual PK, noncompartmental recomputation, population fit or clinical endpoint prediction.","Initial concentration is supplied by the selected preset. Nominal mg/kg dose is a context label, not an administered event or identified body-mass assignment.","The dose-curve coefficients are fixed authored interpolation inputs. Their legacy symbols do not establish mechanistic target-mediated clearance.","Concentration loss and C+loss=C0 use ug/mL, not eliminated drug mass. No source cohort-mean volume/clearance is assigned as a structural compartment.","Exposure and quantitation calculations follow the declared conditional backbone, including mathematical continuation below assay quantitation.","NCA mean/SD references are aggregate observations; absent SD cells are not zero variability and no population intervals are generated."],"name":"Reported-summary initialization, 0.8 mg/kg context","outputs":[{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"plasma_imgn529_ug_mL","label":"Conditional plasma concentration","unit":"ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"auc_h_ug_mL","label":"Exposure (AUC)","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"modeled_remaining_auc_h_ug_mL","label":"Modeled remaining AUC","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"assay_quantitation_ratio","label":"Assay quantitation ratio","unit":"dimensionless"}],"scenario_id":"stathis_dose_0p8_exponential_probe","scientific_questions":["How do the model's key biological readouts change under reported-summary initialization, 0.8 mg/kg context?"],"time_span":{"end":504,"start":0,"step":2}},{"controls":[],"description":"Authored conditional exponential concentration decay from a specified initial concentration and fixed rate; not original patient PK, NCA recomputation or a structural TMDD fit.","interpretation_guardrails":["Authored conditional concentration decay; no original individual PK, noncompartmental recomputation, population fit or clinical endpoint prediction.","Initial concentration is supplied by the selected preset. Nominal mg/kg dose is a context label, not an administered event or identified body-mass assignment.","The dose-curve coefficients are fixed authored interpolation inputs. Their legacy symbols do not establish mechanistic target-mediated clearance.","Concentration loss and C+loss=C0 use ug/mL, not eliminated drug mass. No source cohort-mean volume/clearance is assigned as a structural compartment.","Exposure and quantitation calculations follow the declared conditional backbone, including mathematical continuation below assay quantitation.","NCA mean/SD references are aggregate observations; absent SD cells are not zero variability and no population intervals are generated."],"name":"Reported-summary initialization, 1 mg/kg context","outputs":[{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"plasma_imgn529_ug_mL","label":"Conditional plasma concentration","unit":"ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"auc_h_ug_mL","label":"Exposure (AUC)","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"modeled_remaining_auc_h_ug_mL","label":"Modeled remaining AUC","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"assay_quantitation_ratio","label":"Assay quantitation ratio","unit":"dimensionless"}],"scenario_id":"stathis_dose_1p0_exponential_probe","scientific_questions":["How do the model's key biological readouts change under reported-summary initialization, 1 mg/kg context?"],"time_span":{"end":504,"start":0,"step":2}},{"controls":[],"description":"Authored conditional exponential concentration decay from a specified initial concentration and fixed rate; not original patient PK, NCA recomputation or a structural TMDD fit.","interpretation_guardrails":["Authored conditional concentration decay; no original individual PK, noncompartmental recomputation, population fit or clinical endpoint prediction.","Initial concentration is supplied by the selected preset. Nominal mg/kg dose is a context label, not an administered event or identified body-mass assignment.","The dose-curve coefficients are fixed authored interpolation inputs. Their legacy symbols do not establish mechanistic target-mediated clearance.","Concentration loss and C+loss=C0 use ug/mL, not eliminated drug mass. No source cohort-mean volume/clearance is assigned as a structural compartment.","Exposure and quantitation calculations follow the declared conditional backbone, including mathematical continuation below assay quantitation.","NCA mean/SD references are aggregate observations; absent SD cells are not zero variability and no population intervals are generated."],"name":"Reported-summary initialization, 1.4 mg/kg context","outputs":[{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"plasma_imgn529_ug_mL","label":"Conditional plasma concentration","unit":"ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"auc_h_ug_mL","label":"Exposure (AUC)","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"modeled_remaining_auc_h_ug_mL","label":"Modeled remaining AUC","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"assay_quantitation_ratio","label":"Assay quantitation ratio","unit":"dimensionless"}],"scenario_id":"stathis_dose_1p4_exponential_probe","scientific_questions":["How do the model's key biological readouts change under reported-summary initialization, 1.4 mg/kg context?"],"time_span":{"end":504,"start":0,"step":2}},{"controls":[],"description":"Authored conditional exponential concentration decay from a specified initial concentration and fixed rate; not original patient PK, NCA recomputation or a structural TMDD fit.","interpretation_guardrails":["Authored conditional concentration decay; no original individual PK, noncompartmental recomputation, population fit or clinical endpoint prediction.","Initial concentration is supplied by the selected preset. Nominal mg/kg dose is a context label, not an administered event or identified body-mass assignment.","The dose-curve coefficients are fixed authored interpolation inputs. Their legacy symbols do not establish mechanistic target-mediated clearance.","Concentration loss and C+loss=C0 use ug/mL, not eliminated drug mass. No source cohort-mean volume/clearance is assigned as a structural compartment.","Exposure and quantitation calculations follow the declared conditional backbone, including mathematical continuation below assay quantitation.","NCA mean/SD references are aggregate observations; absent SD cells are not zero variability and no population intervals are generated."],"name":"Reported-summary initialization, 1.8 mg/kg context","outputs":[{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"plasma_imgn529_ug_mL","label":"Conditional plasma concentration","unit":"ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"auc_h_ug_mL","label":"Exposure (AUC)","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"modeled_remaining_auc_h_ug_mL","label":"Modeled remaining AUC","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"assay_quantitation_ratio","label":"Assay quantitation ratio","unit":"dimensionless"}],"scenario_id":"stathis_dose_1p8_exponential_probe","scientific_questions":["How do the model's key biological readouts change under reported-summary initialization, 1.8 mg/kg context?"],"time_span":{"end":504,"start":0,"step":2}},{"controls":[],"description":"Authored conditional exponential concentration decay from a specified initial concentration and fixed rate; not original patient PK, NCA recomputation or a structural TMDD fit.","interpretation_guardrails":["Authored conditional concentration decay; no original individual PK, noncompartmental recomputation, population fit or clinical endpoint prediction.","Initial concentration is supplied by the selected preset. Nominal mg/kg dose is a context label, not an administered event or identified body-mass assignment.","The dose-curve coefficients are fixed authored interpolation inputs. Their legacy symbols do not establish mechanistic target-mediated clearance.","Concentration loss and C+loss=C0 use ug/mL, not eliminated drug mass. No source cohort-mean volume/clearance is assigned as a structural compartment.","Exposure and quantitation calculations follow the declared conditional backbone, including mathematical continuation below assay quantitation.","NCA mean/SD references are aggregate observations; absent SD cells are not zero variability and no population intervals are generated."],"name":"Authored dose-curve initialization, 0.1 mg/kg context","outputs":[{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"plasma_imgn529_ug_mL","label":"Conditional plasma concentration","unit":"ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"auc_h_ug_mL","label":"Exposure (AUC)","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"modeled_remaining_auc_h_ug_mL","label":"Modeled remaining AUC","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"assay_quantitation_ratio","label":"Assay quantitation ratio","unit":"dimensionless"}],"scenario_id":"stathis_exploratory_calibrated_dose_0p1_joint_table4","scientific_questions":["How do the model's key biological readouts change under authored dose-curve initialization, 0.1 mg/kg context?"],"time_span":{"end":504,"start":0,"step":2}},{"controls":[],"description":"Authored conditional exponential concentration decay from a specified initial concentration and fixed rate; not original patient PK, NCA recomputation or a structural TMDD fit.","interpretation_guardrails":["Authored conditional concentration decay; no original individual PK, noncompartmental recomputation, population fit or clinical endpoint prediction.","Initial concentration is supplied by the selected preset. Nominal mg/kg dose is a context label, not an administered event or identified body-mass assignment.","The dose-curve coefficients are fixed authored interpolation inputs. Their legacy symbols do not establish mechanistic target-mediated clearance.","Concentration loss and C+loss=C0 use ug/mL, not eliminated drug mass. No source cohort-mean volume/clearance is assigned as a structural compartment.","Exposure and quantitation calculations follow the declared conditional backbone, including mathematical continuation below assay quantitation.","NCA mean/SD references are aggregate observations; absent SD cells are not zero variability and no population intervals are generated."],"name":"Authored dose-curve initialization, 0.2 mg/kg context","outputs":[{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"plasma_imgn529_ug_mL","label":"Conditional plasma concentration","unit":"ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"auc_h_ug_mL","label":"Exposure (AUC)","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"modeled_remaining_auc_h_ug_mL","label":"Modeled remaining AUC","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"assay_quantitation_ratio","label":"Assay quantitation ratio","unit":"dimensionless"}],"scenario_id":"stathis_exploratory_calibrated_dose_0p2_joint_table4","scientific_questions":["How do the model's key biological readouts change under authored dose-curve initialization, 0.2 mg/kg context?"],"time_span":{"end":504,"start":0,"step":2}},{"controls":[],"description":"Authored conditional exponential concentration decay from a specified initial concentration and fixed rate; not original patient PK, NCA recomputation or a structural TMDD fit.","interpretation_guardrails":["Authored conditional concentration decay; no original individual PK, noncompartmental recomputation, population fit or clinical endpoint prediction.","Initial concentration is supplied by the selected preset. Nominal mg/kg dose is a context label, not an administered event or identified body-mass assignment.","The dose-curve coefficients are fixed authored interpolation inputs. Their legacy symbols do not establish mechanistic target-mediated clearance.","Concentration loss and C+loss=C0 use ug/mL, not eliminated drug mass. No source cohort-mean volume/clearance is assigned as a structural compartment.","Exposure and quantitation calculations follow the declared conditional backbone, including mathematical continuation below assay quantitation.","NCA mean/SD references are aggregate observations; absent SD cells are not zero variability and no population intervals are generated."],"name":"Authored dose-curve initialization, 0.4 mg/kg context","outputs":[{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"plasma_imgn529_ug_mL","label":"Conditional plasma concentration","unit":"ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"auc_h_ug_mL","label":"Exposure (AUC)","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"modeled_remaining_auc_h_ug_mL","label":"Modeled remaining AUC","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"assay_quantitation_ratio","label":"Assay quantitation ratio","unit":"dimensionless"}],"scenario_id":"stathis_exploratory_calibrated_dose_0p4_joint_table4","scientific_questions":["How do the model's key biological readouts change under authored dose-curve initialization, 0.4 mg/kg context?"],"time_span":{"end":504,"start":0,"step":2}},{"controls":[],"description":"Authored conditional exponential concentration decay from a specified initial concentration and fixed rate; not original patient PK, NCA recomputation or a structural TMDD fit.","interpretation_guardrails":["Authored conditional concentration decay; no original individual PK, noncompartmental recomputation, population fit or clinical endpoint prediction.","Initial concentration is supplied by the selected preset. Nominal mg/kg dose is a context label, not an administered event or identified body-mass assignment.","The dose-curve coefficients are fixed authored interpolation inputs. Their legacy symbols do not establish mechanistic target-mediated clearance.","Concentration loss and C+loss=C0 use ug/mL, not eliminated drug mass. No source cohort-mean volume/clearance is assigned as a structural compartment.","Exposure and quantitation calculations follow the declared conditional backbone, including mathematical continuation below assay quantitation.","NCA mean/SD references are aggregate observations; absent SD cells are not zero variability and no population intervals are generated."],"name":"Authored dose-curve initialization, 0.7 mg/kg context","outputs":[{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"plasma_imgn529_ug_mL","label":"Conditional plasma concentration","unit":"ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"auc_h_ug_mL","label":"Exposure (AUC)","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"modeled_remaining_auc_h_ug_mL","label":"Modeled remaining AUC","unit":"h*ug/mL"},{"classification":"provisional","description":"Fixed authored conditional quantity or reference input in the stated unit; not an independent observed patient endpoint.","key":"assay_quantitation_ratio","label":"Assay quantitation ratio","unit":"dimensionless"}],"scenario_id":"stathis_exploratory_calibrated_dose_0p7_joint_table4","scientific_questions":["How do the model's key biological readouts change under authored dose-curve initialization, 0.7 mg/kg context?"],"time_span":{"end":504,"start":0,"step":2}},{"controls":[],"description":"Authored conditional exponential concentration decay from a specified initial concentration and fixed rate; not original patient PK, NCA recomputation or a structural TMDD fit.","interpretation_guardrails":["Authored conditional concentration decay; no original individual PK, noncompartmental recomputation, population fit or clinical endpoint prediction.","Initial concentration is supplied by the selected preset. Nominal mg/kg dose is a context label, not an administered event or identified body-mass assignment.","The dose-curve coefficients are fixed authored interpolation inputs. Their legacy symbols do not establish mechanistic target-mediated clearance.","Concentration loss and C+loss=C0 use ug/mL, not eliminated drug mass. 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intended for replacement by biodistribution data","step":1e-07,"unit":"L/h","value":2e-05}],"description":"Reduces cargo-receptor association tenfold to explore potency attenuation independently of gate-target binding.","interpretation_guardrails":["A receptor-association change may also alter pharmacology not represented by occupancy alone."],"name":"Attenuated cargo-receptor association, 30 nmol IV","outputs":[{"classification":"qualified","description":"Central occupancy predicted from assumed receptor capacity and synthetic kinetic priors; not a safety threshold or clinical biomarker.","key":"central_receptor_occupancy_percent","label":"Systemic cargo receptor occupancy","unit":"%"},{"classification":"qualified","description":"Tumor occupancy predicted from gate retention, opening, and cargo-receptor engagement; not a clinical efficacy claim.","key":"tumor_receptor_occupancy_percent","label":"Tumor cargo receptor occupancy","unit":"%"},{"classification":"qualified","description":"Fraction of the assumed accessible gate capacity occupied by construct.","key":"tumor_gate_occupancy_percent","label":"Tumor gate target occupancy","unit":"%"},{"classification":"qualified","description":"Mass ledger across free, gate-bound, and receptor-bound model states.","key":"total_construct_nmol","label":"Total modeled construct","unit":"nmol"}],"scenario_id":"attenuated_cargo_receptor_30nmol_iv","scientific_questions":["Can cargo-receptor attenuation lower systemic engagement while tumor retention preserves a relative local advantage?"],"time_span":{"end":336,"start":0,"step":6}}],"targets":[{"key":"configurable_tumor_gate_target","label":"configurable tumor gate target"},{"key":"configurable_cargo_receptor","label":"configurable cargo receptor"}],"therapeutics":[{"key":"generic_target_gated_cargo","label":"generic target-gated cargo"}],"unavailable_operations":[{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"2.0.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"Apparent subcutaneous anakinra exposure inhibits empirical CRP production. Fixed responder and waning-sensitivity groups distinguish sustained suppression from rebound under a constant or PK-derived concentration driver.","diseases":[{"key":"systemic_juvenile_idiopathic_arthritis","label":"systemic juvenile idiopathic arthritis"},{"key":"autoinflammatory_syndromes","label":"autoinflammatory syndromes"}],"links":{"page":"/modeling/models/urien-2013-anakinra-conditional-reference","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"recombinant protein","model_classes":["apparent one-compartment SC PK","conditional indirect CRP response"],"model_id":"urien_2013_anakinra_conditional_reference","name":"Anakinra exposure and conditional CRP turnover","outputs":[{"description":"Apparent plasma PK concentration central/(V/F); zero in constant-driver cases without SC dosing.","key":"concentration","label":"PK derived anakinra concentration","unit":"mg/L"},{"description":"Fixed group baseline times normalized CRP response; empirical biomarker output, not patient prediction.","key":"crp","label":"Conditional crp concentration","unit":"mg/L"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"How does bodyweight-projected apparent SC exposure change under a fixed daily administered dose?","interpretation_guardrails":["Conditional fixed-effect exploration only; no clinical dose recommendations, individual patient inference, original fit or population prediction.","Clearance and volume are apparent CL/F and V/F. Unknown physical bioavailability is not identified by the unit dose multiplier or apparent amount ledger.","High-baseline and lower-baseline contexts are fixed conditional groups, not estimated mixture probabilities. Remaining effect sensitivity declines in the waning context; it is not resistance prevalence.","Imposed-concentration contexts drive CRP externally. They do not produce PK concentration or PK exposure without administrations. Clearance and absorption controls are relevant to SC contexts; imposed concentration is relevant only to imposed-driver contexts.","Clearance bounds span retained bodyweight-projected values, but changing clearance alone is not a bodyweight projection. Absorption and turnover ranges are authored 0.5–1.5× default perturbations. Sensitivity-loss bounds span zero to 1.5× the source RESI rate. The imposed-concentration interval spans the source Figure 3 settings and zero. None is a clinical or uncertainty interval.","Bodyweight is resolved into each starting configuration. Dose amounts and volume stay fixed when clearance is edited; choosing a different configuration changes the jointly authored context.","The source between-occasion volume variability, patient observations, BLQ/log10 likelihood, mixed-effects fit and prediction intervals are not reproduced.","No complete source figure panel is reproduced. Calculations use the rounded Table 1 coefficient set. Literal Table 2 uncertainty entries and reported group proportions are retained as source references; they do not establish fitted uncertainty or mixture probabilities for this implementation.","Changing the start resets the supplied initial states; earlier administrations are not reconstructed. Dose-event observations retain their declared pre/post side.","Long coupled histories are mechanistic diagnostics and do not establish observed long-term clinical behavior."],"name":"10 kg, 2 mg/kg/day apparent SC","outputs":[{"classification":"provisional","description":"Apparent plasma PK concentration central/(V/F); zero in constant-driver cases without SC dosing.","key":"concentration","label":"PK derived anakinra concentration","unit":"mg/L"},{"classification":"provisional","description":"Fixed group baseline times normalized CRP response; empirical biomarker output, not patient prediction.","key":"crp","label":"Conditional crp concentration","unit":"mg/L"}],"scenario_id":"PK_bw10_dose2","scientific_questions":["How does bodyweight-projected apparent SC exposure change under a fixed daily administered dose?"],"time_span":{"end":720,"start":0,"step":6}},{"controls":[],"description":"How does bodyweight-projected apparent SC exposure change under a fixed daily administered dose?","interpretation_guardrails":["Conditional fixed-effect exploration only; no clinical dose recommendations, individual patient inference, original fit or population prediction.","Clearance and volume are apparent CL/F and V/F. Unknown physical bioavailability is not identified by the unit dose multiplier or apparent amount ledger.","High-baseline and lower-baseline contexts are fixed conditional groups, not estimated mixture probabilities. Remaining effect sensitivity declines in the waning context; it is not resistance prevalence.","Imposed-concentration contexts drive CRP externally. They do not produce PK concentration or PK exposure without administrations. Clearance and absorption controls are relevant to SC contexts; imposed concentration is relevant only to imposed-driver contexts.","Clearance bounds span retained bodyweight-projected values, but changing clearance alone is not a bodyweight projection. Absorption and turnover ranges are authored 0.5–1.5× default perturbations. Sensitivity-loss bounds span zero to 1.5× the source RESI rate. The imposed-concentration interval spans the source Figure 3 settings and zero. None is a clinical or uncertainty interval.","Bodyweight is resolved into each starting configuration. Dose amounts and volume stay fixed when clearance is edited; choosing a different configuration changes the jointly authored context.","The source between-occasion volume variability, patient observations, BLQ/log10 likelihood, mixed-effects fit and prediction intervals are not reproduced.","No complete source figure panel is reproduced. Calculations use the rounded Table 1 coefficient set. Literal Table 2 uncertainty entries and reported group proportions are retained as source references; they do not establish fitted uncertainty or mixture probabilities for this implementation.","Changing the start resets the supplied initial states; earlier administrations are not reconstructed. Dose-event observations retain their declared pre/post side.","Long coupled histories are mechanistic diagnostics and do not establish observed long-term clinical behavior."],"name":"50 kg, 2 mg/kg/day apparent SC","outputs":[{"classification":"provisional","description":"Apparent plasma PK concentration central/(V/F); zero in constant-driver cases without SC dosing.","key":"concentration","label":"PK derived anakinra concentration","unit":"mg/L"},{"classification":"provisional","description":"Fixed group baseline times normalized CRP response; empirical biomarker output, not patient prediction.","key":"crp","label":"Conditional crp concentration","unit":"mg/L"}],"scenario_id":"PK_bw50_dose2","scientific_questions":["How does bodyweight-projected apparent SC exposure change under a fixed daily administered dose?"],"time_span":{"end":720,"start":0,"step":6}},{"controls":[],"description":"How does fixed exposure and remaining drug-effect sensitivity affect empirical CRP suppression or rebound?","interpretation_guardrails":["Conditional fixed-effect exploration only; no clinical dose recommendations, individual patient inference, original fit or population prediction.","Clearance and volume are apparent CL/F and V/F. Unknown physical bioavailability is not identified by the unit dose multiplier or apparent amount ledger.","High-baseline and lower-baseline contexts are fixed conditional groups, not estimated mixture probabilities. Remaining effect sensitivity declines in the waning context; it is not resistance prevalence.","Imposed-concentration contexts drive CRP externally. They do not produce PK concentration or PK exposure without administrations. Clearance and absorption controls are relevant to SC contexts; imposed concentration is relevant only to imposed-driver contexts.","Clearance bounds span retained bodyweight-projected values, but changing clearance alone is not a bodyweight projection. Absorption and turnover ranges are authored 0.5–1.5× default perturbations. Sensitivity-loss bounds span zero to 1.5× the source RESI rate. The imposed-concentration interval spans the source Figure 3 settings and zero. None is a clinical or uncertainty interval.","Bodyweight is resolved into each starting configuration. Dose amounts and volume stay fixed when clearance is edited; choosing a different configuration changes the jointly authored context.","The source between-occasion volume variability, patient observations, BLQ/log10 likelihood, mixed-effects fit and prediction intervals are not reproduced.","No complete source figure panel is reproduced. Calculations use the rounded Table 1 coefficient set. Literal Table 2 uncertainty entries and reported group proportions are retained as source references; they do not establish fitted uncertainty or mixture probabilities for this implementation.","Changing the start resets the supplied initial states; earlier administrations are not reconstructed. Dose-event observations retain their declared pre/post side.","Long coupled histories are mechanistic diagnostics and do not establish observed long-term clinical behavior."],"name":"Constant PD driver 0.4 mg/L, RESP","outputs":[{"classification":"provisional","description":"Apparent plasma PK concentration central/(V/F); zero in constant-driver cases without SC dosing.","key":"concentration","label":"PK derived anakinra concentration","unit":"mg/L"},{"classification":"provisional","description":"Fixed group baseline times normalized CRP response; empirical biomarker output, not patient prediction.","key":"crp","label":"Conditional crp concentration","unit":"mg/L"}],"scenario_id":"F3_RESP_Css0.4","scientific_questions":["How does fixed exposure and remaining drug-effect sensitivity affect empirical CRP suppression or rebound?"],"time_span":{"end":9600,"start":0,"step":80}},{"controls":[],"description":"How does fixed exposure and remaining drug-effect sensitivity affect empirical CRP suppression or rebound?","interpretation_guardrails":["Conditional fixed-effect exploration only; no clinical dose recommendations, individual patient inference, original fit or population prediction.","Clearance and volume are apparent CL/F and V/F. Unknown physical bioavailability is not identified by the unit dose multiplier or apparent amount ledger.","High-baseline and lower-baseline contexts are fixed conditional groups, not estimated mixture probabilities. Remaining effect sensitivity declines in the waning context; it is not resistance prevalence.","Imposed-concentration contexts drive CRP externally. They do not produce PK concentration or PK exposure without administrations. Clearance and absorption controls are relevant to SC contexts; imposed concentration is relevant only to imposed-driver contexts.","Clearance bounds span retained bodyweight-projected values, but changing clearance alone is not a bodyweight projection. Absorption and turnover ranges are authored 0.5–1.5× default perturbations. Sensitivity-loss bounds span zero to 1.5× the source RESI rate. The imposed-concentration interval spans the source Figure 3 settings and zero. None is a clinical or uncertainty interval.","Bodyweight is resolved into each starting configuration. Dose amounts and volume stay fixed when clearance is edited; choosing a different configuration changes the jointly authored context.","The source between-occasion volume variability, patient observations, BLQ/log10 likelihood, mixed-effects fit and prediction intervals are not reproduced.","No complete source figure panel is reproduced. Calculations use the rounded Table 1 coefficient set. Literal Table 2 uncertainty entries and reported group proportions are retained as source references; they do not establish fitted uncertainty or mixture probabilities for this implementation.","Changing the start resets the supplied initial states; earlier administrations are not reconstructed. Dose-event observations retain their declared pre/post side.","Long coupled histories are mechanistic diagnostics and do not establish observed long-term clinical behavior."],"name":"Constant PD driver 0.4 mg/L, RESI","outputs":[{"classification":"provisional","description":"Apparent plasma PK concentration central/(V/F); zero in constant-driver cases without SC dosing.","key":"concentration","label":"PK derived anakinra concentration","unit":"mg/L"},{"classification":"provisional","description":"Fixed group baseline times normalized CRP response; empirical biomarker output, not patient prediction.","key":"crp","label":"Conditional crp concentration","unit":"mg/L"}],"scenario_id":"F3_RESI_Css0.4","scientific_questions":["How does fixed exposure and remaining drug-effect sensitivity affect empirical CRP suppression or rebound?"],"time_span":{"end":9600,"start":0,"step":80}},{"controls":[],"description":"How does fixed exposure and remaining drug-effect sensitivity affect empirical CRP suppression or rebound?","interpretation_guardrails":["Conditional fixed-effect exploration only; no clinical dose recommendations, individual patient inference, original fit or population prediction.","Clearance and volume are apparent CL/F and V/F. Unknown physical bioavailability is not identified by the unit dose multiplier or apparent amount ledger.","High-baseline and lower-baseline contexts are fixed conditional groups, not estimated mixture probabilities. Remaining effect sensitivity declines in the waning context; it is not resistance prevalence.","Imposed-concentration contexts drive CRP externally. They do not produce PK concentration or PK exposure without administrations. Clearance and absorption controls are relevant to SC contexts; imposed concentration is relevant only to imposed-driver contexts.","Clearance bounds span retained bodyweight-projected values, but changing clearance alone is not a bodyweight projection. Absorption and turnover ranges are authored 0.5–1.5× default perturbations. Sensitivity-loss bounds span zero to 1.5× the source RESI rate. The imposed-concentration interval spans the source Figure 3 settings and zero. None is a clinical or uncertainty interval.","Bodyweight is resolved into each starting configuration. Dose amounts and volume stay fixed when clearance is edited; choosing a different configuration changes the jointly authored context.","The source between-occasion volume variability, patient observations, BLQ/log10 likelihood, mixed-effects fit and prediction intervals are not reproduced.","No complete source figure panel is reproduced. Calculations use the rounded Table 1 coefficient set. Literal Table 2 uncertainty entries and reported group proportions are retained as source references; they do not establish fitted uncertainty or mixture probabilities for this implementation.","Changing the start resets the supplied initial states; earlier administrations are not reconstructed. Dose-event observations retain their declared pre/post side.","Long coupled histories are mechanistic diagnostics and do not establish observed long-term clinical behavior."],"name":"21 kg, RESP, daily conditional SC","outputs":[{"classification":"provisional","description":"Apparent plasma PK concentration central/(V/F); zero in constant-driver cases without SC dosing.","key":"concentration","label":"PK derived anakinra concentration","unit":"mg/L"},{"classification":"provisional","description":"Fixed group baseline times normalized CRP response; empirical biomarker output, not patient prediction.","key":"crp","label":"Conditional crp concentration","unit":"mg/L"}],"scenario_id":"coupled_bw21_RESP","scientific_questions":["How does fixed exposure and remaining drug-effect sensitivity affect empirical CRP suppression or rebound?"],"time_span":{"end":9600,"start":0,"step":80}},{"controls":[],"description":"How does fixed exposure and remaining drug-effect sensitivity affect empirical CRP suppression or rebound?","interpretation_guardrails":["Conditional fixed-effect exploration only; no clinical dose recommendations, individual patient inference, original fit or population prediction.","Clearance and volume are apparent CL/F and V/F. Unknown physical bioavailability is not identified by the unit dose multiplier or apparent amount ledger.","High-baseline and lower-baseline contexts are fixed conditional groups, not estimated mixture probabilities. Remaining effect sensitivity declines in the waning context; it is not resistance prevalence.","Imposed-concentration contexts drive CRP externally. They do not produce PK concentration or PK exposure without administrations. Clearance and absorption controls are relevant to SC contexts; imposed concentration is relevant only to imposed-driver contexts.","Clearance bounds span retained bodyweight-projected values, but changing clearance alone is not a bodyweight projection. Absorption and turnover ranges are authored 0.5–1.5× default perturbations. Sensitivity-loss bounds span zero to 1.5× the source RESI rate. The imposed-concentration interval spans the source Figure 3 settings and zero. None is a clinical or uncertainty interval.","Bodyweight is resolved into each starting configuration. Dose amounts and volume stay fixed when clearance is edited; choosing a different configuration changes the jointly authored context.","The source between-occasion volume variability, patient observations, BLQ/log10 likelihood, mixed-effects fit and prediction intervals are not reproduced.","No complete source figure panel is reproduced. Calculations use the rounded Table 1 coefficient set. Literal Table 2 uncertainty entries and reported group proportions are retained as source references; they do not establish fitted uncertainty or mixture probabilities for this implementation.","Changing the start resets the supplied initial states; earlier administrations are not reconstructed. Dose-event observations retain their declared pre/post side.","Long coupled histories are mechanistic diagnostics and do not establish observed long-term clinical behavior."],"name":"21 kg, RESI, daily conditional SC","outputs":[{"classification":"provisional","description":"Apparent plasma PK concentration central/(V/F); zero in constant-driver cases without SC dosing.","key":"concentration","label":"PK derived anakinra concentration","unit":"mg/L"},{"classification":"provisional","description":"Fixed group baseline times normalized CRP response; empirical biomarker output, not patient prediction.","key":"crp","label":"Conditional crp concentration","unit":"mg/L"}],"scenario_id":"coupled_bw21_RESI","scientific_questions":["How does fixed exposure and remaining drug-effect sensitivity affect empirical CRP suppression or rebound?"],"time_span":{"end":9600,"start":0,"step":80}}],"targets":[{"key":"il1r1","label":"IL1R1"}],"therapeutics":[{"key":"anakinra","label":"anakinra"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.1.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"Two-compartment QSS target-mediated antibody disposition with a direct unbound-concentration capsaicin-challenge response for fixed research histories.","diseases":[{"key":"migraine_prevention_and_cgrp_receptor_pharmacology","label":"Migraine prevention and CGRP-receptor pharmacology","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s11095-017-2183-6","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"links":{"page":"/modeling/models/vu-2017-erenumab-cidbf-pkpd-tmdd","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"Whole mAb","model_classes":["QSS TMDD","Fixed typical-coefficient PK","Direct CIDBF"],"model_id":"vu_2017_erenumab_cidbf_pkpd_tmdd","name":"Erenumab QSS PK and capsaicin response","outputs":[{"description":"Deterministic quantity in the declared physical source coordinate.","key":"unbound_concentration_ng_mL","label":"Unbound concentration","unit":"ng/mL"},{"description":"Deterministic quantity in the declared physical source coordinate.","key":"total_concentration_ng_mL","label":"Total concentration","unit":"ng/mL"},{"description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_inhibition_pct","label":"Cidbf inhibition pct","unit":"percent"},{"description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_delta_dbf_PU","label":"Cidbf delta dbf pu","unit":"PU"},{"description":"Deterministic quantity in the declared physical source coordinate.","key":"accounted_administered_drug_mg","label":"Accounted administered drug","unit":"mg"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Fixed typical-coefficient research history with specified SC or IV input; no population or clinical inference.","interpretation_guardrails":["Fixed source point coefficients and declared SC or IV histories; no original individual fit, population draw or clinical dose advice.","The direct CIDBF quantity is the capsaicin-induced blood-flow increment, not resting or total skin perfusion and not a migraine outcome.","Target capacity and complex use the latent source drug-equivalent ng/mL coordinate, not measured receptor protein mass.","The nominal depot contains the full SC dose and F is applied once in absorption. Drug accounting includes presystemic nonavailability.","The one-hour IV input and complete calendars are declared conditional histories; original infusion duration and source figure traces are not reproduced.","Day coordinates and AUC in ug*day/mL remain physical under alternate time displays."],"name":"7 mg SC Q4W 75 kg deterministic simulation","outputs":[{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"unbound_concentration_ng_mL","label":"Unbound concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"total_concentration_ng_mL","label":"Total concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_inhibition_pct","label":"Cidbf inhibition pct","unit":"percent"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_delta_dbf_PU","label":"Cidbf delta dbf pu","unit":"PU"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"accounted_administered_drug_mg","label":"Accounted administered drug","unit":"mg"}],"scenario_id":"sc_7mg_q4w_75kg_dynamic","scientific_questions":["How do the model's key biological readouts change under 7 mg sc q4w 75 kg deterministic simulation?"],"time_span":{"end":84,"start":0,"step":1}},{"controls":[],"description":"Fixed typical-coefficient research history with specified SC or IV input; no population or clinical inference.","interpretation_guardrails":["Fixed source point coefficients and declared SC or IV histories; no original individual fit, population draw or clinical dose advice.","The direct CIDBF quantity is the capsaicin-induced blood-flow increment, not resting or total skin perfusion and not a migraine outcome.","Target capacity and complex use the latent source drug-equivalent ng/mL coordinate, not measured receptor protein mass.","The nominal depot contains the full SC dose and F is applied once in absorption. Drug accounting includes presystemic nonavailability.","The one-hour IV input and complete calendars are declared conditional histories; original infusion duration and source figure traces are not reproduced.","Day coordinates and AUC in ug*day/mL remain physical under alternate time displays."],"name":"21 mg SC Q4W 75 kg deterministic simulation","outputs":[{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"unbound_concentration_ng_mL","label":"Unbound concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"total_concentration_ng_mL","label":"Total concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_inhibition_pct","label":"Cidbf inhibition pct","unit":"percent"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_delta_dbf_PU","label":"Cidbf delta dbf pu","unit":"PU"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"accounted_administered_drug_mg","label":"Accounted administered drug","unit":"mg"}],"scenario_id":"sc_21mg_q4w_75kg_dynamic","scientific_questions":["How do the model's key biological readouts change under 21 mg sc q4w 75 kg deterministic simulation?"],"time_span":{"end":84,"start":0,"step":1}},{"controls":[],"description":"Fixed typical-coefficient research history with specified SC or IV input; no population or clinical inference.","interpretation_guardrails":["Fixed source point coefficients and declared SC or IV histories; no original individual fit, population draw or clinical dose advice.","The direct CIDBF quantity is the capsaicin-induced blood-flow increment, not resting or total skin perfusion and not a migraine outcome.","Target capacity and complex use the latent source drug-equivalent ng/mL coordinate, not measured receptor protein mass.","The nominal depot contains the full SC dose and F is applied once in absorption. Drug accounting includes presystemic nonavailability.","The one-hour IV input and complete calendars are declared conditional histories; original infusion duration and source figure traces are not reproduced.","Day coordinates and AUC in ug*day/mL remain physical under alternate time displays."],"name":"70 mg SC Q4W 75 kg deterministic simulation","outputs":[{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"unbound_concentration_ng_mL","label":"Unbound concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"total_concentration_ng_mL","label":"Total concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_inhibition_pct","label":"Cidbf inhibition pct","unit":"percent"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_delta_dbf_PU","label":"Cidbf delta dbf pu","unit":"PU"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"accounted_administered_drug_mg","label":"Accounted administered drug","unit":"mg"}],"scenario_id":"sc_70mg_q4w_75kg_dynamic","scientific_questions":["How do the model's key biological readouts change under 70 mg sc q4w 75 kg deterministic simulation?"],"time_span":{"end":84,"start":0,"step":1}},{"controls":[],"description":"Fixed typical-coefficient research history with specified SC or IV input; no population or clinical inference.","interpretation_guardrails":["Fixed source point coefficients and declared SC or IV histories; no original individual fit, population draw or clinical dose advice.","The direct CIDBF quantity is the capsaicin-induced blood-flow increment, not resting or total skin perfusion and not a migraine outcome.","Target capacity and complex use the latent source drug-equivalent ng/mL coordinate, not measured receptor protein mass.","The nominal depot contains the full SC dose and F is applied once in absorption. Drug accounting includes presystemic nonavailability.","The one-hour IV input and complete calendars are declared conditional histories; original infusion duration and source figure traces are not reproduced.","Day coordinates and AUC in ug*day/mL remain physical under alternate time displays."],"name":"21 mg SC Q4W 68 kg Supplementary Fig. S8 simulation","outputs":[{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"unbound_concentration_ng_mL","label":"Unbound concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"total_concentration_ng_mL","label":"Total concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_inhibition_pct","label":"Cidbf inhibition pct","unit":"percent"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_delta_dbf_PU","label":"Cidbf delta dbf pu","unit":"PU"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"accounted_administered_drug_mg","label":"Accounted administered drug","unit":"mg"}],"scenario_id":"sc_21mg_q4w_68kg_s8_dynamic","scientific_questions":["How do the model's key biological readouts change under 21 mg sc q4w 68 kg supplementary fig. s8 simulation?"],"time_span":{"end":175,"start":0,"step":1}},{"controls":[],"description":"Fixed typical-coefficient research history with specified SC or IV input; no population or clinical inference.","interpretation_guardrails":["Fixed source point coefficients and declared SC or IV histories; no original individual fit, population draw or clinical dose advice.","The direct CIDBF quantity is the capsaicin-induced blood-flow increment, not resting or total skin perfusion and not a migraine outcome.","Target capacity and complex use the latent source drug-equivalent ng/mL coordinate, not measured receptor protein mass.","The nominal depot contains the full SC dose and F is applied once in absorption. Drug accounting includes presystemic nonavailability.","The one-hour IV input and complete calendars are declared conditional histories; original infusion duration and source figure traces are not reproduced.","Day coordinates and AUC in ug*day/mL remain physical under alternate time displays."],"name":"21 mg SC Q4W 84 kg Supplementary Fig. S8 simulation","outputs":[{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"unbound_concentration_ng_mL","label":"Unbound concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"total_concentration_ng_mL","label":"Total concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_inhibition_pct","label":"Cidbf inhibition pct","unit":"percent"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_delta_dbf_PU","label":"Cidbf delta dbf pu","unit":"PU"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"accounted_administered_drug_mg","label":"Accounted administered drug","unit":"mg"}],"scenario_id":"sc_21mg_q4w_84kg_s8_dynamic","scientific_questions":["How do the model's key biological readouts change under 21 mg sc q4w 84 kg supplementary fig. s8 simulation?"],"time_span":{"end":175,"start":0,"step":1}},{"controls":[],"description":"Fixed typical-coefficient research history with specified SC or IV input; no population or clinical inference.","interpretation_guardrails":["Fixed source point coefficients and declared SC or IV histories; no original individual fit, population draw or clinical dose advice.","The direct CIDBF quantity is the capsaicin-induced blood-flow increment, not resting or total skin perfusion and not a migraine outcome.","Target capacity and complex use the latent source drug-equivalent ng/mL coordinate, not measured receptor protein mass.","The nominal depot contains the full SC dose and F is applied once in absorption. Drug accounting includes presystemic nonavailability.","The one-hour IV input and complete calendars are declared conditional histories; original infusion duration and source figure traces are not reproduced.","Day coordinates and AUC in ug*day/mL remain physical under alternate time displays."],"name":"70 mg SC Q4W 68 kg Supplementary Fig. S8 simulation","outputs":[{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"unbound_concentration_ng_mL","label":"Unbound concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"total_concentration_ng_mL","label":"Total concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_inhibition_pct","label":"Cidbf inhibition pct","unit":"percent"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_delta_dbf_PU","label":"Cidbf delta dbf pu","unit":"PU"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"accounted_administered_drug_mg","label":"Accounted administered drug","unit":"mg"}],"scenario_id":"sc_70mg_q4w_68kg_s8_dynamic","scientific_questions":["How do the model's key biological readouts change under 70 mg sc q4w 68 kg supplementary fig. s8 simulation?"],"time_span":{"end":175,"start":0,"step":1}},{"controls":[],"description":"Fixed typical-coefficient research history with specified SC or IV input; no population or clinical inference.","interpretation_guardrails":["Fixed source point coefficients and declared SC or IV histories; no original individual fit, population draw or clinical dose advice.","The direct CIDBF quantity is the capsaicin-induced blood-flow increment, not resting or total skin perfusion and not a migraine outcome.","Target capacity and complex use the latent source drug-equivalent ng/mL coordinate, not measured receptor protein mass.","The nominal depot contains the full SC dose and F is applied once in absorption. Drug accounting includes presystemic nonavailability.","The one-hour IV input and complete calendars are declared conditional histories; original infusion duration and source figure traces are not reproduced.","Day coordinates and AUC in ug*day/mL remain physical under alternate time displays."],"name":"70 mg SC Q4W 84 kg Supplementary Fig. S8 simulation","outputs":[{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"unbound_concentration_ng_mL","label":"Unbound concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"total_concentration_ng_mL","label":"Total concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_inhibition_pct","label":"Cidbf inhibition pct","unit":"percent"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_delta_dbf_PU","label":"Cidbf delta dbf pu","unit":"PU"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"accounted_administered_drug_mg","label":"Accounted administered drug","unit":"mg"}],"scenario_id":"sc_70mg_q4w_84kg_s8_dynamic","scientific_questions":["How do the model's key biological readouts change under 70 mg sc q4w 84 kg supplementary fig. s8 simulation?"],"time_span":{"end":175,"start":0,"step":1}},{"controls":[],"description":"Fixed typical-coefficient research history with specified SC or IV input; no population or clinical inference.","interpretation_guardrails":["Fixed source point coefficients and declared SC or IV histories; no original individual fit, population draw or clinical dose advice.","The direct CIDBF quantity is the capsaicin-induced blood-flow increment, not resting or total skin perfusion and not a migraine outcome.","Target capacity and complex use the latent source drug-equivalent ng/mL coordinate, not measured receptor protein mass.","The nominal depot contains the full SC dose and F is applied once in absorption. Drug accounting includes presystemic nonavailability.","The one-hour IV input and complete calendars are declared conditional histories; original infusion duration and source figure traces are not reproduced.","Day coordinates and AUC in ug*day/mL remain physical under alternate time displays."],"name":"140 mg IV single-infusion deterministic simulation","outputs":[{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"unbound_concentration_ng_mL","label":"Unbound concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"total_concentration_ng_mL","label":"Total concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_inhibition_pct","label":"Cidbf inhibition pct","unit":"percent"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_delta_dbf_PU","label":"Cidbf delta dbf pu","unit":"PU"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"accounted_administered_drug_mg","label":"Accounted administered drug","unit":"mg"}],"scenario_id":"iv_140mg_single_infusion_dynamic","scientific_questions":["How do the model's key biological readouts change under 140 mg iv single-infusion deterministic simulation?"],"time_span":{"end":84,"start":0,"step":1}},{"controls":[],"description":"Fixed typical-coefficient research history with specified SC or IV input; no population or clinical inference.","interpretation_guardrails":["Fixed source point coefficients and declared SC or IV histories; no original individual fit, population draw or clinical dose advice.","The direct CIDBF quantity is the capsaicin-induced blood-flow increment, not resting or total skin perfusion and not a migraine outcome.","Target capacity and complex use the latent source drug-equivalent ng/mL coordinate, not measured receptor protein mass.","The nominal depot contains the full SC dose and F is applied once in absorption. Drug accounting includes presystemic nonavailability.","The one-hour IV input and complete calendars are declared conditional histories; original infusion duration and source figure traces are not reproduced.","Day coordinates and AUC in ug*day/mL remain physical under alternate time displays."],"name":"21 mg SC Q4W 75 kg Supplementary Fig. S8 simulation","outputs":[{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"unbound_concentration_ng_mL","label":"Unbound concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"total_concentration_ng_mL","label":"Total concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_inhibition_pct","label":"Cidbf inhibition pct","unit":"percent"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_delta_dbf_PU","label":"Cidbf delta dbf pu","unit":"PU"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"accounted_administered_drug_mg","label":"Accounted administered drug","unit":"mg"}],"scenario_id":"sc_21mg_q4w_75kg_s8_dynamic","scientific_questions":["How do the model's key biological readouts change under 21 mg sc q4w 75 kg supplementary fig. s8 simulation?"],"time_span":{"end":175,"start":0,"step":1}},{"controls":[],"description":"Fixed typical-coefficient research history with specified SC or IV input; no population or clinical inference.","interpretation_guardrails":["Fixed source point coefficients and declared SC or IV histories; no original individual fit, population draw or clinical dose advice.","The direct CIDBF quantity is the capsaicin-induced blood-flow increment, not resting or total skin perfusion and not a migraine outcome.","Target capacity and complex use the latent source drug-equivalent ng/mL coordinate, not measured receptor protein mass.","The nominal depot contains the full SC dose and F is applied once in absorption. Drug accounting includes presystemic nonavailability.","The one-hour IV input and complete calendars are declared conditional histories; original infusion duration and source figure traces are not reproduced.","Day coordinates and AUC in ug*day/mL remain physical under alternate time displays."],"name":"70 mg SC Q4W 75 kg Supplementary Fig. S8 simulation","outputs":[{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"unbound_concentration_ng_mL","label":"Unbound concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"total_concentration_ng_mL","label":"Total concentration","unit":"ng/mL"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_inhibition_pct","label":"Cidbf inhibition pct","unit":"percent"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"cidbf_delta_dbf_PU","label":"Cidbf delta dbf pu","unit":"PU"},{"classification":"provisional","description":"Deterministic quantity in the declared physical source coordinate.","key":"accounted_administered_drug_mg","label":"Accounted administered drug","unit":"mg"}],"scenario_id":"sc_70mg_q4w_75kg_s8_dynamic","scientific_questions":["How do the model's key biological readouts change under 70 mg sc q4w 75 kg supplementary fig. s8 simulation?"],"time_span":{"end":175,"start":0,"step":1}}],"targets":[{"key":"cgrp_receptor","label":"CGRP receptor"}],"therapeutics":[{"key":"erenumab","label":"Erenumab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.3.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"A conditional two-compartment model of vedolizumab exposure in adult allogeneic stem-cell transplant research. Fixed body weight, albumin, lymphocyte count, age and GvHD flags alter clearance and distribution. It does not predict treatment outcomes, reconstruct changing patient covariates or quantify population uncertainty.","diseases":[{"key":"gvhd_prophylaxis_in_adults_undergoing_allo_hsct","label":"GvHD prophylaxis in adults undergoing allo-HSCT"}],"links":{"page":"/modeling/models/waterhouse-2024-vedolizumab-gvhd-allohsct-poppk","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"Whole mAb","model_classes":["Other/Unclassified"],"model_id":"waterhouse_2024_vedolizumab_gvhd_allohsct_poppk","name":"Vedolizumab exposure across transplant covariates","outputs":[{"description":"Copy of central amount divided by the safeguarded conditional central volume. mg/L and ug/mL have equal numerical scale here, so this is the same concentration as the existing primary concentration readout, not an additional independent observation or evidence endpoint. Fixed-covariate deterministic exposure excludes patient and population uncertainty.","key":"central_concentration_mg_per_L","label":"Conditional central concentration diagnostic","unit":"mg/L"},{"description":"Integral from the simulation start; an AUC interval must be selected before comparing exposure across regimens.","key":"cumulative_auc_mg_day_per_L","label":"Cumulative central exposure","unit":"mg*day/L"},{"description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"description":"Conditional drug-accounting quantity; not a biological compartment or observed patient endpoint.","key":"current_systemic_drug_mg","label":"Current systemic drug","unit":"mg"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. 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Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_body_weight_51kg_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under body weight 51kg relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"body weight 56kg relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. 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Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"body weight 65kg relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. 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Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"body weight 75kg relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. 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Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_body_weight_105kg_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under body weight 105kg relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"body weight 111kg relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_body_weight_111kg_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under body weight 111kg relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"age 23y relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_age_23y_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under age 23y relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"age 27y relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_age_27y_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under age 27y relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"age 39y relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_age_39y_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under age 39y relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"age 55y relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_age_55y_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under age 55y relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"age 64y relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_age_64y_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under age 64y relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"age 68y relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_age_68y_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under age 68y relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"age 70y relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_age_70y_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under age 70y relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"albumin 29gl relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_albumin_29gl_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under albumin 29gl relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"albumin 32gl relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_albumin_32gl_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under albumin 32gl relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"albumin 36gl relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_albumin_36gl_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under albumin 36gl relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"albumin 40gl relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_albumin_40gl_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under albumin 40gl relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"albumin 43gl relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_albumin_43gl_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under albumin 43gl relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"albumin 46gl relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_albumin_46gl_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under albumin 46gl relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"albumin 48gl relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_albumin_48gl_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under albumin 48gl relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"lymphocyte 0kul relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_lymphocyte_0kul_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under lymphocyte 0kul relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"lymphocyte 0 1kul relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_lymphocyte_0_1kul_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under lymphocyte 0 1kul relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"lymphocyte 0 5kul relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_lymphocyte_0_5kul_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under lymphocyte 0 5kul relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"lymphocyte 1kul relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_lymphocyte_1kul_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under lymphocyte 1kul relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"lymphocyte 1 7kul relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_lymphocyte_1_7kul_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under lymphocyte 1 7kul relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"lymphocyte 2 3kul relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_lymphocyte_2_3kul_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under lymphocyte 2 3kul relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"liver gvhd relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_liver_gvhd_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under liver gvhd relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"skin gvhd relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_skin_gvhd_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under skin gvhd relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Calculated relative-clearance probe at fixed covariates; no drug administration.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"intestine gvhd relative cl check","outputs":[{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Reference central volume multiplied by the fixed body-weight factor. Reports the unfloored apparent volume definition; concentration uses its existing positive denominator safeguard. Not measured anatomical volume, a fitted individual volume or population random-effect draw.","key":"covariate_central_volume_l","label":"Conditional central distribution volume","unit":"L"},{"classification":"provisional","description":"Intercompartmental clearance after the fixed weight factor. Multiply it by the applicable compartment concentration to obtain a one-way amount-transfer rate.","key":"covariate_intercompartmental_clearance_l_per_day","label":"Conditional intercompartmental clearance","unit":"L/day"}],"scenario_id":"fig3_intestine_gvhd_relative_cl_check","scientific_questions":["How do the model's key biological readouts change under intestine gvhd relative cl check?"],"time_span":{"end":1,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate exposure with explicit fixed-mass intravenous infusions.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"Three-infusion reference exposure","outputs":[{"classification":"provisional","description":"Copy of central amount divided by the safeguarded conditional central volume. mg/L and ug/mL have equal numerical scale here, so this is the same concentration as the existing primary concentration readout, not an additional independent observation or evidence endpoint. Fixed-covariate deterministic exposure excludes patient and population uncertainty.","key":"central_concentration_mg_per_L","label":"Conditional central concentration diagnostic","unit":"mg/L"},{"classification":"provisional","description":"Integral from the simulation start; an AUC interval must be selected before comparing exposure across regimens.","key":"cumulative_auc_mg_day_per_L","label":"Cumulative central exposure","unit":"mg*day/L"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Conditional drug-accounting quantity; not a biological compartment or observed patient endpoint.","key":"current_systemic_drug_mg","label":"Current systemic drug","unit":"mg"}],"scenario_id":"phase1b_300mg_days_m1_13_42_reference","scientific_questions":["How do the model's key biological readouts change under three-infusion reference exposure?"],"time_span":{"end":180,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate exposure with explicit fixed-mass intravenous infusions.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"Repeated-infusion reference exposure","outputs":[{"classification":"provisional","description":"Copy of central amount divided by the safeguarded conditional central volume. mg/L and ug/mL have equal numerical scale here, so this is the same concentration as the existing primary concentration readout, not an additional independent observation or evidence endpoint. Fixed-covariate deterministic exposure excludes patient and population uncertainty.","key":"central_concentration_mg_per_L","label":"Conditional central concentration diagnostic","unit":"mg/L"},{"classification":"provisional","description":"Integral from the simulation start; an AUC interval must be selected before comparing exposure across regimens.","key":"cumulative_auc_mg_day_per_L","label":"Cumulative central exposure","unit":"mg*day/L"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Conditional drug-accounting quantity; not a biological compartment or observed patient endpoint.","key":"current_systemic_drug_mg","label":"Current systemic drug","unit":"mg"}],"scenario_id":"phase3_300mg_q4w_reference","scientific_questions":["How do the model's key biological readouts change under repeated-infusion reference exposure?"],"time_span":{"end":180,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate exposure with explicit fixed-mass intravenous infusions.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"Lower body weight","outputs":[{"classification":"provisional","description":"Copy of central amount divided by the safeguarded conditional central volume. mg/L and ug/mL have equal numerical scale here, so this is the same concentration as the existing primary concentration readout, not an additional independent observation or evidence endpoint. Fixed-covariate deterministic exposure excludes patient and population uncertainty.","key":"central_concentration_mg_per_L","label":"Conditional central concentration diagnostic","unit":"mg/L"},{"classification":"provisional","description":"Integral from the simulation start; an AUC interval must be selected before comparing exposure across regimens.","key":"cumulative_auc_mg_day_per_L","label":"Cumulative central exposure","unit":"mg*day/L"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Conditional drug-accounting quantity; not a biological compartment or observed patient endpoint.","key":"current_systemic_drug_mg","label":"Current systemic drug","unit":"mg"}],"scenario_id":"phase3_300mg_low_weight_51kg","scientific_questions":["How do the model's key biological readouts change under lower body weight?"],"time_span":{"end":180,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate exposure with explicit fixed-mass intravenous infusions.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"Higher body weight","outputs":[{"classification":"provisional","description":"Copy of central amount divided by the safeguarded conditional central volume. mg/L and ug/mL have equal numerical scale here, so this is the same concentration as the existing primary concentration readout, not an additional independent observation or evidence endpoint. Fixed-covariate deterministic exposure excludes patient and population uncertainty.","key":"central_concentration_mg_per_L","label":"Conditional central concentration diagnostic","unit":"mg/L"},{"classification":"provisional","description":"Integral from the simulation start; an AUC interval must be selected before comparing exposure across regimens.","key":"cumulative_auc_mg_day_per_L","label":"Cumulative central exposure","unit":"mg*day/L"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. This ratio reports the deterministic conditional coefficient; it is not a newly estimated clearance, exposure ratio, probability, clinical effect or time-varying patient clearance.","key":"relative_clearance_to_reference","label":"Conditional clearance ratio","unit":"dimensionless"},{"classification":"provisional","description":"Conditional drug-accounting quantity; not a biological compartment or observed patient endpoint.","key":"current_systemic_drug_mg","label":"Current systemic drug","unit":"mg"}],"scenario_id":"phase3_300mg_high_weight_105kg","scientific_questions":["How do the model's key biological readouts change under higher body weight?"],"time_span":{"end":180,"start":0,"step":1}},{"controls":[],"description":"Conditional fixed-covariate exposure with explicit fixed-mass intravenous infusions.","interpretation_guardrails":["Conditional two-compartment IV PK with fixed covariates, zero individual deviations and explicit fixed-dose infusions.","Thirty calculated covariate-effect contexts contain no drug; they report relative clearance and disposition coefficients.","Exactly zero lymphocytes are represented by 0.01 K/uL in the covariate expression; every positive input retains its supplied value.","The administration clock is days since the first infusion; the clinical-study Day -1 is represented by simulation day zero.","Exposure and eliminated amount are nonfeedback observers; elapsed time and the constant marker are diagnostic coordinates.","Reported statistical values are source-reference information. Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"Lower albumin","outputs":[{"classification":"provisional","description":"Copy of central amount divided by the safeguarded conditional central volume. mg/L and ug/mL have equal numerical scale here, so this is the same concentration as the existing primary concentration readout, not an additional independent observation or evidence endpoint. Fixed-covariate deterministic exposure excludes patient and population uncertainty.","key":"central_concentration_mg_per_L","label":"Conditional central concentration diagnostic","unit":"mg/L"},{"classification":"provisional","description":"Integral from the simulation start; an AUC interval must be selected before comparing exposure across regimens.","key":"cumulative_auc_mg_day_per_L","label":"Cumulative central exposure","unit":"mg*day/L"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance. Exact zero lymphocytes use 0.01 K/uL; positive values remain unchanged.","key":"covariate_clearance_l_per_day","label":"Conditional clearance","unit":"L/day"},{"classification":"provisional","description":"Fixed covariate-adjusted clearance divided by the supplied reference clearance. 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Population sampling, fitting, patient-history reconstruction and clinical-response prediction are outside this candidate."],"name":"Higher albumin","outputs":[{"classification":"provisional","description":"Copy of central amount divided by the safeguarded conditional central volume. mg/L and ug/mL have equal numerical scale here, so this is the same concentration as the existing primary concentration readout, not an additional independent observation or evidence endpoint. 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units as declared.","key":"concentration_ug_per_mL","label":"Concentration","unit":"ug/mL"},{"description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"AUC_ug_day_per_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"eliminated_mg","label":"Eliminated","unit":"mg"},{"description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"accounted_drug_mg","label":"Accounted drug","unit":"mg"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Fixed circulating-PK example with supplied covariates, individual coordinates and explicit central mg infusions; 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no original patient or cohort reconstruction.","interpretation_guardrails":["Interpret patterns within this model and starting configuration; do not treat them as clinical predictions or treatment recommendations."],"name":"Fixed q3w covariate contrast: female","outputs":[{"classification":"provisional","description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"concentration_ug_per_mL","label":"Concentration","unit":"ug/mL"},{"classification":"provisional","description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"AUC_ug_day_per_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"eliminated_mg","label":"Eliminated","unit":"mg"},{"classification":"provisional","description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"accounted_drug_mg","label":"Accounted drug","unit":"mg"}],"scenario_id":"jtail_q3w_fixed_female","scientific_questions":["How do the model's key biological readouts change under fixed q3w covariate contrast: female?"],"time_span":{"end":42,"start":0,"step":0.0208333}},{"controls":[],"description":"Fixed circulating-PK example with supplied covariates, individual coordinates and explicit central mg infusions; no original patient or cohort reconstruction.","interpretation_guardrails":["Interpret patterns within this model and starting configuration; do not treat them as clinical predictions or treatment recommendations."],"name":"Fixed q3w covariate contrast: ada positive","outputs":[{"classification":"provisional","description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"concentration_ug_per_mL","label":"Concentration","unit":"ug/mL"},{"classification":"provisional","description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"AUC_ug_day_per_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"eliminated_mg","label":"Eliminated","unit":"mg"},{"classification":"provisional","description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"accounted_drug_mg","label":"Accounted drug","unit":"mg"}],"scenario_id":"jtail_q3w_fixed_ada_positive","scientific_questions":["How do the model's key biological readouts change under fixed q3w covariate contrast: ada positive?"],"time_span":{"end":42,"start":0,"step":0.0208333}},{"controls":[],"description":"Fixed circulating-PK example with supplied covariates, individual coordinates and explicit central mg infusions; no original patient or cohort reconstruction.","interpretation_guardrails":["Interpret patterns within this model and starting configuration; do not treat them as clinical predictions or treatment recommendations."],"name":"Fixed q3w covariate contrast: female ada positive","outputs":[{"classification":"provisional","description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"concentration_ug_per_mL","label":"Concentration","unit":"ug/mL"},{"classification":"provisional","description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"AUC_ug_day_per_mL","label":"Exposure (AUC)","unit":"ug*day/mL"},{"classification":"provisional","description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"eliminated_mg","label":"Eliminated","unit":"mg"},{"classification":"provisional","description":"Named conditional PK state, observer or diagnostic; units as declared.","key":"accounted_drug_mg","label":"Accounted drug","unit":"mg"}],"scenario_id":"jtail_q3w_fixed_female_ada_positive","scientific_questions":["How do the model's key biological readouts change under fixed q3w covariate contrast: female ada positive?"],"time_span":{"end":42,"start":0,"step":0.0208333}}],"targets":[{"key":"pdl1","label":"PD-L1 / CD274","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1016/j.jtocrr.2024.100683","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"therapeutics":[{"key":"atezolizumab","label":"Atezolizumab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.3.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"Two-compartment IV disposition with fixed baseline covariates, specified individual effects and integrated drug elimination.","diseases":[{"key":"advanced_malignancies","label":"Advanced malignancies","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s10928-021-09739-y","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"links":{"page":"/modeling/models/yang-2021-cemiplimab-advanced-malignancies-poppk","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"Whole mAb","model_classes":["Two-compartment PK","Time-varying clearance","Fixed covariates"],"model_id":"yang_2021_cemiplimab_advanced_malignancies_poppk","name":"Cemiplimab pharmacokinetics with time-varying clearance","outputs":[{"description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; 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Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. 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An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Mean-covariate individual 350 mg Q3W IV regimen","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"dynamic_typical_350mg_q3w","scientific_questions":["How do the model's key biological readouts change under mean-covariate individual 350 mg q3w iv regimen?"],"time_span":{"end":168,"start":0,"step":7}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. 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An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"High body-weight fixed-dose probe","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"dynamic_high_weight_350mg_q3w","scientific_questions":["How do the model's key biological readouts change under high body-weight fixed-dose probe?"],"time_span":{"end":168,"start":0,"step":7}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. 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An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Mean-covariate individual 1 mg/kg Q2W IV regimen","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"dynamic_typical_1mgkg_q2w","scientific_questions":["How do the model's key biological readouts change under mean-covariate individual 1 mg/kg q2w iv regimen?"],"time_span":{"end":168,"start":0,"step":7}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. 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An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Mean-covariate individual 10 mg/kg Q2W IV regimen","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"dynamic_typical_10mgkg_q2w","scientific_questions":["How do the model's key biological readouts change under mean-covariate individual 10 mg/kg q2w iv regimen?"],"time_span":{"end":168,"start":0,"step":7}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. 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An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Mean-covariate individual 200 mg Q2W IV regimen","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"dynamic_typical_200mg_q2w","scientific_questions":["How do the model's key biological readouts change under mean-covariate individual 200 mg q2w iv regimen?"],"time_span":{"end":168,"start":0,"step":7}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. 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An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Mean-covariate individual 3 mg/kg Q3W IV regimen","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"dynamic_typical_3mgkg_q3w","scientific_questions":["How do the model's key biological readouts change under mean-covariate individual 3 mg/kg q3w iv regimen?"],"time_span":{"end":168,"start":0,"step":7}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Supplementary Figure 1 clearance-time fixed-effect probe","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"suppfig1_clearance_timecourse_fixed_effect_probe","scientific_questions":["How do the model's key biological readouts change under supplementary figure 1 clearance-time fixed-effect probe?"],"time_span":{"end":504,"start":0,"step":28}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"1mgkg q2w — median covariates","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_1mgkg_q2w_median_covariates","scientific_questions":["How do the model's key biological readouts change under 1mgkg q2w — median covariates?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"3mgkg q2w — median covariates","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_3mgkg_q2w_median_covariates","scientific_questions":["How do the model's key biological readouts change under 3mgkg q2w — median covariates?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"10mgkg q2w — median covariates","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_10mgkg_q2w_median_covariates","scientific_questions":["How do the model's key biological readouts change under 10mgkg q2w — median covariates?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"200mg q2w — median covariates","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_200mg_q2w_median_covariates","scientific_questions":["How do the model's key biological readouts change under 200mg q2w — median covariates?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"3mgkg q3w — median covariates","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_3mgkg_q3w_median_covariates","scientific_questions":["How do the model's key biological readouts change under 3mgkg q3w — median covariates?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"350mg q3w — median covariates","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_median_covariates","scientific_questions":["How do the model's key biological readouts change under 350mg q3w — median covariates?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"350mg q3w — body weight kg low","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_body_weight_kg_low","scientific_questions":["How do the model's key biological readouts change under 350mg q3w — body weight kg low?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"350mg q3w — body weight kg high","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_body_weight_kg_high","scientific_questions":["How do the model's key biological readouts change under 350mg q3w — body weight kg high?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"350mg q3w — albumin g L low","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_albumin_g_L_low","scientific_questions":["How do the model's key biological readouts change under 350mg q3w — albumin g l low?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"350mg q3w — albumin g L high","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_albumin_g_L_high","scientific_questions":["How do the model's key biological readouts change under 350mg q3w — albumin g l high?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"350mg q3w — igg g L low","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_igg_g_L_low","scientific_questions":["How do the model's key biological readouts change under 350mg q3w — igg g l low?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"350mg q3w — igg g L high","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_igg_g_L_high","scientific_questions":["How do the model's key biological readouts change under 350mg q3w — igg g l high?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"350mg q3w — alt IU L low","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_alt_IU_L_low","scientific_questions":["How do the model's key biological readouts change under 350mg q3w — alt iu l low?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"350mg q3w — alt IU L high","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_alt_IU_L_high","scientific_questions":["How do the model's key biological readouts change under 350mg q3w — alt iu l high?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"350mg q3w — bmi kg m2 low","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_bmi_kg_m2_low","scientific_questions":["How do the model's key biological readouts change under 350mg q3w — bmi kg m2 low?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"350mg q3w — bmi kg m2 high","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_bmi_kg_m2_high","scientific_questions":["How do the model's key biological readouts change under 350mg q3w — bmi kg m2 high?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Specified lower shared CL/Q individual coefficient","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_eta_clq_minus_sd","scientific_questions":["How do the model's key biological readouts change under specified lower shared cl/q individual coefficient?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Specified higher shared CL/Q individual coefficient","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_eta_clq_plus_sd","scientific_questions":["How do the model's key biological readouts change under specified higher shared cl/q individual coefficient?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Specified lower shared V2/V3 individual coefficient","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_eta_vss_minus_sd","scientific_questions":["How do the model's key biological readouts change under specified lower shared v2/v3 individual coefficient?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Specified higher shared V2/V3 individual coefficient","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_eta_vss_plus_sd","scientific_questions":["How do the model's key biological readouts change under specified higher shared v2/v3 individual coefficient?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Specified lower maximum log-clearance change individual coefficient","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_eta_emax_minus_sd","scientific_questions":["How do the model's key biological readouts change under specified lower maximum log-clearance change individual coefficient?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Specified higher maximum log-clearance change individual coefficient","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_eta_emax_plus_sd","scientific_questions":["How do the model's key biological readouts change under specified higher maximum log-clearance change individual coefficient?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Specified lower log-effect midpoint individual coefficient","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_eta_t50_minus_sd","scientific_questions":["How do the model's key biological readouts change under specified lower log-effect midpoint individual coefficient?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Conditional deterministic cemiplimab exposure with fixed baseline covariates and specified individual log multipliers.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Specified higher log-effect midpoint individual coefficient","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"source_350mg_q3w_eta_t50_plus_sd","scientific_questions":["How do the model's key biological readouts change under specified higher log-effect midpoint individual coefficient?"],"time_span":{"end":168,"start":0,"step":1}},{"controls":[],"description":"Specified baseline covariates and individual coefficients with a single350mg input; clearance follows its empirical time function.","interpretation_guardrails":["Deterministic drug disposition only; no PD-1 binding, immune-cell, tumor response or clinical dosing prediction.","Covariates and four individual log-effects stay fixed throughout each condition. Fixed sensitivities are not sampled subjects or population percentiles.","Median covariate normalization is an explicit implementation convention; the original fit and likelihood are not recovered.","The selected T50 reference branch has no categorical race prediction.","AUC, eliminated mass and elapsed time are nonfeedback observers. Cumulative elimination integrates instantaneous CL times central concentration.","T50 is the half-log-clearance-effect time. The instantaneous frozen-matrix half-time and Vss/CL approximation are diagnostics, not observed terminal half-lives.","Each history specifies 30-minute IV infusions. An infusion beginning at the observation endpoint contributes no delivered mass before that endpoint.","No original cohort fit, observation-noise sampling, population predictive check, arbitrary control-range qualification or individual dose advice is provided."],"name":"Specified reference clearance over365days","outputs":[{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"central_conc_mg_L","label":"Central conc","unit":"mg/L"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"CL_ind_L_day","label":"Clearance ind","unit":"L/day"},{"classification":"provisional","description":"Fixed-context model quantity in the stated physical unit.","key":"AUC_day_mg_L","label":"Exposure (AUC)","unit":"day*mg/L"},{"classification":"provisional","description":"Current central plus peripheral amount and integrated cumulative elimination.","key":"accounted_cemiplimab_mg","label":"Accounted cemiplimab","unit":"mg"}],"scenario_id":"declared_typical_clearance_reference_365day","scientific_questions":["How do the model's key biological readouts change under specified reference clearance over365days?"],"time_span":{"end":365,"start":0,"step":5}}],"targets":[{"key":"pd1","label":"PD-1 / PDCD1","review":{"date":null,"reviewer":null,"status":"source_supported_unreviewed"},"source":{"doi":"10.1007/s10928-021-09739-y","locator":"Retained primary-reference pharmacological context, same DOI as the prior governed catalog.","relationship":"Context tag only; this does not assert that the entity is an explicit mechanistic state or a qualified clinical use."}}],"therapeutics":[{"key":"cemiplimab","label":"Cemiplimab"}],"unavailable_operations":[{"execution":"governed_run","max_runs":25,"operation":"pkpd.parameter_scan","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_parameter_scan_not_released"},{"execution":"governed_run","operation":"pkpd.fit_data","qualified":false,"unavailability_category":"fit_contract","unavailable_reason":"model_fit_contract_not_qualified"},{"execution":"governed_run","operation":"pkpd.optimize_regimen","qualified":false,"unavailability_category":"model_release_scope","unavailable_reason":"model_regimen_optimization_not_released"}],"version":"0.3.1"},{"availability":{"catalog_qualified":true,"released":true},"description":"Subcutaneous ustekinumab absorption, systemic distribution and elimination under the reported reference priors, with explicit exposure and amount accounting.","diseases":[{"key":"inflammatory_bowel_disease","label":"Inflammatory bowel disease"}],"links":{"page":"/modeling/models/yarur-2025-ustekinumab-clearance-ibd-pk","preview":"/api/v1/runs/preview","submit":"/api/v1/runs"},"minimum_plan":"free","modality":"monoclonal antibody","model_classes":["two-compartment SC PK","Table 1 reference-prior projection"],"model_id":"yarur_2025_ustekinumab_clearance_ibd_pk","name":"Ustekinumab exposure and baseline covariates","outputs":[{"description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"clearance_l_day","label":"Clearance","unit":"L/day"},{"description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"qualified_operations":[{"execution":"public_metadata","operation":"compare_public_metadata","qualified":true},{"execution":"public_metadata","operation":"inspect_public_evidence","qualified":true},{"execution":"governed_run","operation":"pkpd.simulate_scenario","qualified":true}],"regimen_optimization":[],"scenarios":[{"controls":[],"description":"Prospective regular SC dosing from explicitly drug-free initial conditions; Table 1 reference priors.","interpretation_guardrails":["Table 1 reference-parameter PK projection; fixed priors are not individual posterior clearance estimates.","Zero initial drug is a declared prospective assumption. The measured cohort had prior induction and at least 16 weeks therapy.","Dose calendars are authored regular 90 mg SC schedules through the displayed interval; original patient dose histories are unavailable.","No weight scaling is inferred from the current table; arbitrary weight-dependent individual predictions are unavailable.","Antibody-positive status is an external-prior covariate exploration; all observed current-study cycles were antibody negative.","Exposure and amount-accounting observers are derived additions and do not predict disease control.","No cohort-median matching, statistical fitting, posterior inference, population sampling or clinical-response prediction is performed."],"name":"90mg sc q8w reference","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"clearance_l_day","label":"Clearance","unit":"L/day"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"90mg-sc-q8w-reference","scientific_questions":["How do the model's key biological readouts change under 90mg sc q8w reference?"],"time_span":{"end":336,"start":0,"step":1}},{"controls":[],"description":"Prospective regular SC dosing from explicitly drug-free initial conditions; Table 1 reference priors.","interpretation_guardrails":["Table 1 reference-parameter PK projection; fixed priors are not individual posterior clearance estimates.","Zero initial drug is a declared prospective assumption. The measured cohort had prior induction and at least 16 weeks therapy.","Dose calendars are authored regular 90 mg SC schedules through the displayed interval; original patient dose histories are unavailable.","No weight scaling is inferred from the current table; arbitrary weight-dependent individual predictions are unavailable.","Antibody-positive status is an external-prior covariate exploration; all observed current-study cycles were antibody negative.","Exposure and amount-accounting observers are derived additions and do not predict disease control.","No cohort-median matching, statistical fitting, posterior inference, population sampling or clinical-response prediction is performed."],"name":"90mg sc q4w reference","outputs":[{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"central_concentration_mg_l","label":"Central concentration","unit":"mg/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"auc_mg_day_l","label":"Exposure (AUC)","unit":"mg*day/L"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"clearance_l_day","label":"Clearance","unit":"L/day"},{"classification":"provisional","description":"Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.","key":"accounted_amount_mg","label":"Accounted amount","unit":"mg"}],"scenario_id":"90mg-sc-q4w-reference","scientific_questions":["How do the model's key biological readouts change under 90mg sc q4w reference?"],"time_span":{"end":336,"start":0,"step":1}},{"controls":[],"description":"Prospective regular SC dosing from explicitly drug-free initial conditions; Table 1 reference priors.","interpretation_guardrails":["Table 1 reference-parameter PK projection; fixed priors are not individual posterior clearance estimates.","Zero initial drug is a declared prospective assumption. 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