The landscape of Alzheimer's disease clinical trials is facing mounting scrutiny over its lack of diverse patient representation, despite the condition's impact across all demographic groups. This disparity has recently come into sharp focus following discussions at an FDA Advisory Committee meeting regarding Eli Lilly's Alzheimer's drug Kisunla (donanemab).
Current State of Trial Demographics
The TRAILBLAZER-ALZ 2 study, which led to Kisunla's approval, reported 90.9% white participants in its treatment group. Similarly, Eisai's CLARITY AD trial for Leqembi (lecanemab) included 76.3% white patients, highlighting a persistent pattern of homogeneous enrollment.
Dr. Jorge Llibre, assistant professor of neurology at Washington University School of Medicine in St. Louis, points out a critical paradox: "Minority populations are at greater risk for Alzheimer's, but the absence of adequate data describing these subgroups makes it difficult to enroll a diverse patient population."
Screening Criteria Barriers
A significant challenge lies in the validation of eligibility criteria. Recent analysis of the Phase III AHEAD trial revealed that participants from underrepresented groups often fail to meet existing amyloid plasma A𝛽42/40 requirements, despite having higher dementia risk. Dr. Llibre questions the foundation of these standards: "The cutoffs we use for Alzheimer's disease are defined in a 95% non-Hispanic population. So when a patient does not meet a cutoff, my question is, which cutoff?"
Impact on Patient Care
Dr. Joy Snider, director of the Knight Alzheimer Disease Research Center Clinical Trials Unit, emphasizes the clinical implications: "When we go to treat people in the clinic and are counseling patients who are going to get these medications, we can't say a lot of people like you have gotten this drug [in trials], because they haven't."
Structural and Resource Challenges
Multiple barriers impede diverse enrollment:
- Financial constraints: Participants often need support for transportation, childcare, and lost wages
- Access limitations: Trial centers are frequently not located in minority communities
- Language barriers: Many research centers lack multilingual capabilities
- Trust issues: Insufficient representation of diverse communities among research staff
Moving Toward Solutions
Dr. Marc Agronin, CMO at Frank C. and Lynn Scaduto MIND Institute, emphasizes the need for comprehensive education programs within communities of color. Additionally, experts recommend:
- Developing new eligibility criteria validated across diverse populations
- Increasing compensation for trial participation
- Establishing research centers in underserved communities
- Ensuring trial materials are available in multiple languages
- Building research teams that reflect target communities
The approval of new treatments like Leqembi and Kisunla has made addressing these disparities more urgent than ever. As Dr. Llibre notes, "The overwhelming majority of research centers are not prepared to enroll diverse communities despite verbalizing their goals of diverse recruitment."
