ArticleCPT: pharmacometrics & systems pharmacology2022
Efficient and relevant stepwise covariate model building for pharmacometrics.
Article in CPT: pharmacometrics & systems pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Exposure-Efficacy Meta-Model of Nintedanib in Adult Patients With Chronic Fibrosing Interstitial Lung Diseases.CPT: pharmacometrics & systems pharmacology · 2026Pooled it
- Covariate Model Selection Approaches for Population Pharmacokinetics: A Systematic Review of Existing Methods, From SCM to AI.CPT: pharmacometrics & systems pharmacology · 2025Pooled it
- Population Pharmacokinetics and Pharmacodynamics of Depemokimab in People with Asthma and Chronic Rhinosinusitis with Nasal Polyps.Journal of clinical pharmacology · 2026Trial
- Population Pharmacokinetics and Exposure-Response Model-Based Bayesian Extrapolation of FVC-Based Efficacy Endpoints From Adults to Pediatric Patients Receiving Nintedanib.CPT: pharmacometrics & systems pharmacology · 2026Trial
- A Phase 2a Study of the Early Bactericidal Activity of Rifampicin in Combination With Meropenem Plus Amoxicillin/Clavulanate Among Adults With Rifampicin-Resistant Pulmonary Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Trial
- Phase 2 multicenter study of pegaspargase in Japanese patients with previously untreated acute lymphoblastic leukemia.International journal of hematology · 2025Trial
- Donanemab exposure-response in early symptomatic Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Exposure-response modeling of liver fat imaging endpoints in non-alcoholic fatty liver disease populations administered ervogastat alone and co-administered with clesacostat.CPT: pharmacometrics & systems pharmacology · 2025Trial
- Population pharmacokinetic analysis of quizartinib in patients with newly diagnosed FLT3-internal-tandem-duplication-positive acute myeloid leukemia.Clinical and translational science · 2024Trial
- Concentration-QTcF analysis of quizartinib in patients with newly diagnosed FLT3-internal-tandem-duplication-positive acute myeloid leukemia.Clinical and translational science · 2024Trial
- Model-Based Analysis with Mechanistic Insights to CAR-T-Cell Therapy Kinetics: Case Study with Axicabtagene Ciloleucel and Brexucabtagene Autoleucel.Clinical pharmacology and therapeutics · 2026Article
- Population Pharmacokinetics of Subcutaneous Infliximab: A Real-World Study of Naïve and Switch Patients.Pharmaceutics · 2026Article
- Exposure-Response Analyses of Datopotamab Deruxtecan (Dato-DXd), a TROP2-Directed Antibody-Drug Conjugate, in Advanced Non-small Cell Lung Cancer.Clinical pharmacology and therapeutics · 2026Article
- AI-Powered Lesion-Level Tumor Growth Inhibition Modeling Improves Model Stability and Prognostic Association With PFS.CPT: pharmacometrics & systems pharmacology · 2026Article
- Population Pharmacokinetics and Pharmacokinetics-Pharmacodynamics Analyses of Elafibranor to Support Dose Selection in Primary Biliary Cholangitis.CPT: pharmacometrics & systems pharmacology · 2026Article
- PKGPT: Expert-Orchestrated Recursive LLM Agent for Automated NONMEM PopPK Modeling with Human Benchmarking.Pharmaceutics · 2026Article
- Assessing Covariate Clinical Relevance in High-Dimensional PK Analysis: A Comparison of SCM+, FFEM, and FREM Approaches.CPT: pharmacometrics & systems pharmacology · 2026Article
- Learning Covariate Relations in Disease Progression Models Using Symbolic Neural Networks.CPT: pharmacometrics & systems pharmacology · 2026Article
- Stochastic Gates for Covariate Selection in Population Pharmacokinetics Modeling.CPT: pharmacometrics & systems pharmacology · 2026Article
- Exposure-Response Modeling of Monthly Migraine Days for Efficacy of Atogepant in Patients With Episodic or Chronic Migraine.CPT: pharmacometrics & systems pharmacology · 2026Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Covariate modeling is an important opportunity for pharmacometrics to influence decision making in drug development. The stepwise covariate model (SCM) building procedure is the most common method for covariate model development. Despite its advantages, the traditional SCM method is known to have long runtimes and the suboptimal ability to select relevant covariates, especially in more complex phase III settings. In this work, two alternative approaches are presented: SCM+, which introduces the "adaptive scope reduction" and changes to general estimation settings, and "stage-wise filtering," which groups covariates into categories based on their importance (mechanistic, structural, and exploratory). The three methods (SCM, SCM+, and SCM+ with stage-wise filtering) are applied to data from a simulated phase III population pharmacokinetic study and are compared in terms of efficiency and relevance. The two SCM+ methods were considerably more efficient than the traditional SCM: the number of function evaluations was reduced by 70% for SCM+ and by 76% for SCM+ with stage-wise filtering compared to SCM; the corresponding number of executed models was reduced by 44% for SCM+ and 70% for SCM+ with stage-wise filtering. In addition, among the three methods, SCM+ with stage-wise filtering selected the highest number of relevant covariates. Given the improved efficiency and ability to select relevant covariates shown in this work, the use of SCM+ and stage-wise filtering can greatly increase the efficiency of covariate modeling in drug development, which will ultimately facilitate more timely support for decision making.
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