Thomas M. Shiovitz,MD , Earle E. Bain,MD, David J. McCann, PhD, Phil Skolnick, PhD, Thomas Laughren,MD, Adam Hanina,MBA, and Daniel Burch,MD
The Journal of Clinical Pharmacology 2016, 56(9) 1151–1164 C 2016, The American College of Clinical Pharmacology DOI: 10.1002/jcph.689
Accounting for subject nonadherence and eliminating inappropriate subjects in clinical trials are critical elements of a successful study.Nonadherence can increase variance, lower study power, and reduce the magnitude of treatment effects. Inappropriate subjects (including those who do not have the illness under study, fail to report exclusionary conditions, falsely report medication adherence, or participate in concurrent trials) confound safety and efficacy signals. This paper, a product of the International Society for CNS Clinical Trial Methodology (ISCTM)Working Group on Nonadherence in Clinical Trials, explores and models nonadherence in clinical trials and puts forth specific recommendations to identify and mitigate its negative effects. These include statistical analyses of nonadherence data, novel protocol design, and the use of biomarkers, subject registries, and/or medication adherence technologies.