ArticleJournal of pharmacokinetics and pharmacodynamics2017
Model selection and averaging of nonlinear mixed-effect models for robust phase III dose selection.
Article in Journal of pharmacokinetics and pharmacodynamics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed.
- Integration of individual preclinical and clinical anti-infective PKPD data to predict clinical study outcomes.Clinical and translational science · 2024Trial
- Improved Confidence in a Confirmatory Stage by Application of Item-Based Pharmacometrics Model: Illustration with a Phase III Active Comparator-Controlled Trial in COPD Patients.Pharmaceutical research · 2022Trial
- Effect of remdesivir on viral dynamics in COVID-19 hospitalized patients: a modelling analysis of the randomized, controlled, open-label DisCoVeRy trial.The Journal of antimicrobial chemotherapy · 2022Trial
- Improved Decision-Making Confidence Using Item-Based Pharmacometric Model: Illustration with a Phase II Placebo-Controlled Trial.The AAPS journal · 2021Trial
- Population PK/PD Modeling for Evaluation of Intertwining Effects of Drug and Disease on Thrombocytopenia in Acute Leukemias.CPT: pharmacometrics & systems pharmacology · 2026Article
- Overcoming Model Uncertainty - How Equivalence Tests Can Benefit From Model Averaging.Statistics in medicine · 2025Article
- Comparative Analysis of Traditional and Pharmacometric-Based Pharmacoeconomic Modeling in the Cost-Utility Evaluation of Sunitinib Therapy.PharmacoEconomics · 2025Article
- Evaluation of model-integrated evidence approaches for pharmacokinetic bioequivalence studies using model averaging methods.CPT: pharmacometrics & systems pharmacology · 2024Article
- Development and comparison of model-integrated evidence approaches for bioequivalence studies with pharmacokinetic end points.CPT: pharmacometrics & systems pharmacology · 2024Article
- The Role of Model Master Files for Sharing, Acceptance, and Communication with FDA.The AAPS journal · 2024Article
- Statistical recommendations for count, binary, and ordinal data in rare disease cross-over trials.Orphanet journal of rare diseases · 2023Article
- Treatment of evolving cancers will require dynamic decision support.Annals of oncology : official journal of the European Society for Medical Oncology · 2023Review
- Robust and Adaptive Two-stage Designs in Nonlinear Mixed Effect Models.The AAPS journal · 2023Article
- External Evaluation of Population Pharmacokinetic Models for Precision Dosing: Current State and Knowledge Gaps.Clinical pharmacokinetics · 2023Article
- Comparison of Seven Non-Linear Mixed Effect Model-Based Approaches to Test for Treatment Effect.Pharmaceutics · 2023Article
- Optimization of trial duration to predict long-term HbA1c change with therapy: A pharmacometrics simulation-based evaluation.CPT: pharmacometrics & systems pharmacology · 2022Article
- Application of Machine Learning Classification to Improve the Performance of Vancomycin Therapeutic Drug Monitoring.Pharmaceutics · 2022Article
- Pharmacometrics meets statistics-A synergy for modern drug development.CPT: pharmacometrics & systems pharmacology · 2021Article
- Dose-Response Mixed Models for Repeated Measures - a New Method for Assessment of Dose-Response.Pharmaceutical research · 2020Article
- Model Averaging in Viral Dynamic Models.The AAPS journal · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Population model-based (pharmacometric) approaches are widely used for the analyses of phase IIb clinical trial data to increase the accuracy of the dose selection for phase III clinical trials. On the other hand, if the analysis is based on one selected model, model selection bias can potentially spoil the accuracy of the dose selection process. In this paper, four methods that assume a number of pre-defined model structure candidates, for example a set of dose-response shape functions, and then combine or select those candidate models are introduced. The key hypothesis is that by combining both model structure uncertainty and model parameter uncertainty using these methodologies, we can make a more robust model based dose selection decision at the end of a phase IIb clinical trial. These methods are investigated using realistic simulation studies based on the study protocol of an actual phase IIb trial for an oral asthma drug candidate (AZD1981). Based on the simulation study, it is demonstrated that a bootstrap model selection method properly avoids model selection bias and in most cases increases the accuracy of the end of phase IIb decision. Thus, we recommend using this bootstrap model selection method when conducting population model-based decision-making at the end of phase IIb clinical trials.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.