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From Trial and Error to Trial Simulation III: A Framework for Interim Analysis in Efficacy Trials With Antidepressant Drugs
Author(s) -
Santen G,
Zwet E,
Bettica P,
Gomeni RA,
Danhof M,
Della Pasqua O
Publication year - 2011
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2011.11
Subject(s) - interim , interim analysis , clinical trial , clinical pharmacology , medicine , adaptive design , antidepressant , bayesian probability , medical physics , intensive care medicine , pharmacology , computer science , artificial intelligence , archaeology , hippocampus , history
Clinical trials with antidepressant drugs often fail to detect drug effect, even with drugs that are known to be efficacious. In a previous publication, we showed that a model‐based approach is required to address some of the existing challenges in the design of clinical trial protocols. Here, we illustrate how the implementation of an interim analysis (IA) may help to identify studies that are headed for failure, early in the trial before completion of treatment. In contrast to traditional IA procedures, an adaptive Bayesian approach is proposed to optimize the timing of analysis and decision criteria for futility and efficacy, taking into account enrollment rate and treatment response at intermediate visits in the trial. Validation procedures involving re‐enrollment of patients confirmed the performance of the method. Our findings reveal that optimization of the timing and decision criteria at the interim stage is critical for the accuracy of the conclusions about treatment efficacy or futility. Clinical Pharmacology & Therapeutics (2011) 89 4, 602–607. doi: 10.1038/clpt.2011.11