title: Mitigating the Effects of Nonadherence in Clinical Trials.
abstract: 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.
authors.affiliation: California Neuroscience Research Medical Group, Sherman Oaks, CA, USA.|CTSdatabase, LLC, Beverly Hills, CA, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Shiovitz
authors.affiliation: Global Pharmaceutical Research and Development, AbbVie, Inc, North Chicago, IL, USA.
authors.forename: Earle E
authors.initials: EE
authors.lastname: Bain
authors.affiliation: Division of Therapeutics and Medical Consequences, NIDA, NIH, Bethesda, MD, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: McCann
authors.affiliation: Division of Therapeutics and Medical Consequences, NIDA, NIH, Bethesda, MD, USA.
authors.forename: Phil
authors.initials: P
authors.lastname: Skolnick
authors.affiliation: Director of Regulatory Affairs, Massachusetts General Hospital Clinical Trial Network and Institute, Boston, MA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Laughren
authors.affiliation: AiCure, New York, NY, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Hanina
authors.affiliation: Pharmaceutical Product Development, LLC, Wilmington, NC, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Burch
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards*; D005260:Female; D006801:Humans; D038622:Internationality; D008297:Male; D055118:Medication Adherence / Q000523:psychology; D010349:Patient Compliance / Q000523:psychology*; D010358:Patient Participation / Q000379:methods / Q000523:psychology
keywords: adherence; clinical trials; duplicate subjects; nonadherence; professional subjects