Open AccessA Systematic Evaluation of Effect of Adherence Patterns on the Sample Size and Power of a Clinical Study
Author(s) -
Mallayasamy Surulivelrajan,
Chaturvedula Ayyappa,
Blaschke Terrence,
Fossler Michael J.
Publication year - 2018
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12361
Subject(s) - sample size determination , medicine , pharmacodynamics , clinical trial , placebo , population , sample (material) , pharmacokinetics , pharmacology , statistics , mathematics , alternative medicine , chemistry , environmental health , pathology , chromatography
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.