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.

Potential Role of Antipsychotic-Galantamine-Memantine Combination in the Treatment of Positive, Cognitive, and Negative Symptoms of Schizophrenia

“…However, both studies used a weekly pill count and medication review to check for adherence, which is not a foolproof method [90], and only participants who received 75% or more of their assigned study medication were included in the analysis [62, 89]. Efficacy signal detection may be enhanced in future RCTs if all of these issues are addressed.…”

Safety, Science, or Both? Deceptive Healthy Volunteers: Psychiatric Conditions Uncovered by Objective Methods of Screening

“…Industry-sponsored trials pay investigators by enrolled subjects while screening is inadequately reimbursed, which impacts the quality of enrolled participants (28, 30). In recent years, placebo response rates have increased in major depressive disorder (MDD) trials, with a consequent decrease of treatment effects (31).…”

“…Moreover, some IRBs require listing of eligibility criteria in informed consents. Overly stringent eligibility criteria may give professional volunteers advantage over appropriate participants (30). Potential harms of deception are shown in Table 2.…”

Selected Concepts on Ethics in Biopharmaceutical Innovation

“…The design of the study research protocols should be closely strict and rigorous in order to have a good scientific data and correct output, in order to conserve the patient's benefits, behind every efficient and successful research therapy an adherence to research protocols, in case of the absence or non-adherence to this protocols, lack of caution or any information or technical error, can lead to an unfavorable and disadvantages outcomes also can expose the human subject to risks, complex his disease, reduce the therapy trial efficacy chances, decrease the human subject's life quality and even can lead him to death [19][20][21]. Moreover, the bad adherence can complicate the research process and give rise to several difficulties which push the clinicians and researchers to do additional processes, therefore, wasting of time and efforts also huge financial losses [22,23].…”