TY - JOUR
T1 - A Systematic Evaluation of Effect of Adherence Patterns on the Sample Size and Power of a Clinical Study
AU - Mallayasamy, Surulivelrajan
AU - Chaturvedula, Ayyappa
AU - Blaschke, Terrence
AU - Fossler, Michael J.
N1 - Publisher Copyright:
© 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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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U2 - 10.1002/psp4.12361
DO - 10.1002/psp4.12361
M3 - Article
C2 - 30291680
AN - SCOPUS:85055726563
SN - 2163-8306
VL - 7
SP - 818
EP - 828
JO - CPT: Pharmacometrics and Systems Pharmacology
JF - CPT: Pharmacometrics and Systems Pharmacology
IS - 12
ER -