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CPT Pharmacometrics Syst Pharmacol. 2018 Dec;7(12):818-828. doi: 10.1002/psp4.12361. Epub 2018 Oct 28.

A Systematic Evaluation of Effect of Adherence Patterns on the Sample Size and Power of a Clinical Study.

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UNTHSC, University of North Texas System College of Pharmacy, Fort Worth, Texas, USA.
Stanford University School of Medicine, Stanford, California, USA.
Clinical Operations and Quantitative Sciences, Trevena, Inc., Chesterbrook, Pennsylvania, USA.


The objective of our study was to evaluate the effect of adherence patterns on the sample size and power of a clinical trial. Simulations from a population pharmacokinetic/pharmacodynamic (PK/PD) model linked to an adherence model were used. Four types of drug characteristics, such as long (~35 hours) and short (~12 hours) half-life in combination with earlier or delayed time to reach steady-state PD end points were studied. Adherence patterns were simulated using Markov chains. Our results clearly demonstrate the significant impact of varying levels and patterns of nonadherence on the sample size and power of a study. For drugs with short half-lives the evidence to support efficacy could be diluted by various patterns of nonadherence that would make its efficacy indistinguishable from the response to placebo. Prospectively utilizing clinical trial simulations with thorough incorporation of various adherence patterns would provide valuable information when designing a trial.

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