Diversity in Alzheimer’s Disease drug trials: The importance of eligibility criteria

Abstract

BackgroundTo generalize safety and efficacy findings, it is essential that diverse populations are well represented in global Alzheimer’s disease (AD) drug trials. In this review, we aimed to 1) investigate participant diversity in disease‐modifying AD trials over time, 2) identify which eligibility criteria were used and how they were defined, and 3) how the eligibility criteria may have affected participant diversity levels.MethodA systematic review of amyloid and tau trials in Alzheimer’s disease was performed using Medline, Embase, the Cochrane Library, and Clinicaltrials.gov, identifying 2247 records.ResultIn the 101 included AD trials, participants were predominantly white (median percentage: 94.7%, IQR: 81.0%‐96.7%); and this percentage showed no significant increase or decrease over time (2001‐2019). Eligibility criteria such as exclusion of persons with psychiatric illness (78.2%), cardiovascular disease (71.3%) and cerebrovascular disease (68.3%), obligated caregiver attendance (80.2%), and specific MMSE‐scores (90.1%; no significant increase/decrease over time, Fig. 1) may have led to a disproportionate exclusion of ethnoracially diverse individuals. Furthermore, many eligibility criteria—such as those describing diabetes, hepatic disease, and renal conditions—often were not well defined, or the cut‐offs varied considerably across studies.ConclusionEthnoracially diverse participants continue to be underrepresented in AD clinical trials. Several recommendations will be provided, such as the use of internationally recognized clinical classifications and cut‐offs, inclusion of participants with specific medical conditions as long as they are medically stable, and flexibility in requirements regarding caregiver attendance. Furthermore, changes need to be considered to 1) the instruments used in trials (e.g. overreliance on MMSE) and 2) requirements regarding education, literacy, and language.

Underrepresented and Underserved Populations in Neurological Research

“…They are still frequently inaccessible to underrepresented and underserved communities. Eligibility criteria that disproportionately exclude individuals with comorbid conditions, 59 60 requirement of a study partner with obliged study visit attendance, 59 60 and lack of flexibility in visit scheduling have all been reported as barriers to inclusion. Neurological research studies can also be burdensome to participants and introduce physical risks and opportunity costs.…”