5 Cognitive, Emotional, and Functional Predictors of Clinical Trial Enrollment

Abstract

Objective:With participant recruitment being a top barrier to AD research progress, the rate of screen failure in Alzheimer’s disease (AD) clinical trials is unsustainable. Although steps have been undertaken to consider solutions to the continued recruitment shortage, there is unfortunately minimal emphasis on reducing screen failure rates based on study inclusion criteria. Here we present information attempting to understand the cognitive, emotional, and functional features of individuals who failed screening measures for AD trials.Participants and Methods:The current study is a retrospective, cross-sectional analysis. Thirty-eight participants (aged 50-83) having (1) previously received a clinical diagnostic workup at a transdisciplinary cognitive specialty clinic and (2) previously screened for a specific industry-sponsored clinical trial of MCI/early AD (EMERGE) met inclusion criteria. Previously collected clinical data were analyzed to identify predictors of AD trial screen pass/fail status.Results:Of the 38 participants in the current study, 14 screen passed into this AD clinical trial, and 24 screen failed. Higher screen failure rates were significantly related to gender, with 83% of female participants screen failing this AD trial versus 45% of male participants. There was no difference in age or education between screen pass/fail groups, nor were differences present for performance on visual or verbal memory tasks, or the MOCA. Conversely, those participants screen failing this AD clinical trial performed significantly worse on nonmemory cognitive domains pertaining to general fund of knowledge, working memory, and executive functioning. Additionally, the screen fail group reported greater levels of anxiety, but not depression nor endorsements on a measure of functional status.Conclusions:Worse performance on non-memory neuropsychological domains was related to screen failure status for the EMERGE AD clinical trial. This finding may be explained by the traditional recruitment pathway from clinic to trials, which beyond the diagnosis of interest is up to the opinion of the physician to determine “fit” for a trial. Higher screen failure rates may result from physicians erroneously viewing more globally-impaired patients as being more appropriate for an AD clinical trial, resulting in greater tendencies towards recruiting patients who are too severe to meet inclusion criteria for a trial. Recruiting patients into clinical trials earlier in their disease course - when disease severity is less - may result in reduced screen failure rates in AD trials. That we could not detect a relationship between memory-related tasks and screen fail/pass status may be explained by either (1) the measures used in the EMERGE trial were not as sensitive to subtle changes in memory, or (2) that memory dysfunction is necessary for a diagnosis of AD but not sufficient to distinguish who will be successfully screened into an AD clinical trial. Overall, these findings have the potential to advance the field by reducing screen failure rates in AD clinical trials by using information already available to clinical trial teams, which will enhance trial-recruitment infrastructure and encourage greater engagement of older adults in AD research.