AN EVALUATION OF INDEPENDENT SUBJECT ELIGIBILITY REVIEWS TO ENSURE ENROLLMENT OF HIGH QUALITY APPROPRIATE SUBJECTS IN MILD ALZHEIMER’S DISEASE (AD) TRIALS

The enrollment of appropriate subjects with mild AD is crucial to ensure valid and reliable data in clinical trials. It is essential to follow a refined set of diagnostic criteria to accurately represent the targeted population. The enrollment of ineligible subjects can adversely influence study outcomes, including an increase in incomplete data due to subject variables that may contribute to high rates of discontinuation, as well as unreliable data if subjects are not representative of the larger population of interest (Grill, 2010). This analysis examines the benefits of implementing a third-party clinician review of mild AD subject eligibility in a double-blind placebo controlled trial. This review was based on established questions corresponding to protocol inclusion and exclusionary criteria following National Institute of Neurological and Communicative Disorders Association and the Alzheimer's disease and Related Disorders Association recommendations (McKhann, 2011). Each eligibility review was required to be completed prior to randomization and included a thorough examination across areas of diagnostics, psychiatric and neuropsychological history, demographics, functional abilities and impairments, level of caregiver involvement, medical history and concomitant medication. The review was completed for 2180 subjects across 189 sites and 19 countries by trained members of a clinical assessment team. Data suggested that of 2180 subjects identified for enrollment by local site staff, 486 did not progress beyond the Screening period. The most salient reasons, in order of frequency, are: sites’ initial review of inclusion and exclusion criteria (including lab results), protocol deviations and withdrawn consents. The third party independent review further determined that of those 1694 subjects deemed appropriate by sites to continue an additional 11% or 188 subjects were not appropriate for randomization based on more rigorous examination. Results suggest that a small but significant percentage of subjects can be further identified as ineligible in a post independent review. A total of 188 subjects were prevented from being inappropriately randomized into this trial. Had these subjects been enrolled the study sample may not have accurately reflected inclusion criteria, potentially increasing instances of early discontinuation and possibly deleteriously impacting study outcomes regarding efficacy and safety.