Race- and Sex-Based Disparities in Alzheimer’s Disease Clinical Trial Enrollment in the United States and Canada: An Indigenous Perspective

Abstract

Randomized clinical trials (RCT) involve labor-intensive, highly regulated, and controlled processes intended to transform scientific concepts into clinical outcomes. To be effective and targeted, it is imperative they include those populations who would most benefit from those outcomes. Alzheimer's disease (AD) is most detrimental to the aging population, and its clinical manifestation is influenced by socioeconomic factors such as poverty, poor education, stress, and chronic comorbidities. Indigenous populations in the United States and Canada are among the minority populations most influenced by poor socioeconomic conditions and are prone to the ravages of AD, with Indigenous women carrying the added burden of exposure to violence, caregiving stresses, and increased risk by virtue of their sex. Race-and sex-based disparities in RCT enrollment has occurred for decades, with Indigenous men and women very poorly represented. In this review, we examined literature from the last twenty years that reinforce these disparities and provide some concrete suggestions and guidelines to increase the enrollment numbers in AD RCT among this vulnerable and poorly represented population.

Recommendations to address key recruitment challenges of Alzheimer's disease clinical trials

“…Their trial participation has been suppressed by mistrust of clinical research based on historical mistreatment, language and cultural barriers, and limited access to health care, among other barriers 7,9,26 . Moreover, inadequate targeted recruitment of diverse groups has exacerbated the underrepresentation of high‐risk populations and limited our understanding of whether biomarker and pathological changes are similar across groups 9,23,25,27–29 . These groups are also less likely to receive a timely AD diagnosis, and therefore when they are diagnosed, the diagnosis typically comes in the later stages of the disease when their symptoms are more debilitating 30 .…”

“…7,9,26 Moreover, inadequate targeted recruitment of diverse groups has exacerbated the underrepresentation of high-risk populations and limited our understanding of whether biomarker and pathological changes are similar across groups. 9,23,25,[27][28][29] These groups are also less likely to receive a timely AD diagnosis, and therefore when they are diagnosed, the diagnosis typically comes in the later stages of the disease when their symptoms are more debilitating. 30 This barrier is particularly important to overcome if we are to advance AD clinical research that is equitable and represents the full range of the AD patient population.…”

Genetic risk scores and dementia risk across different ethnic groups in UK Biobank

“…A lack of disease modifying treatments and growing evidence for dementia prevention [ 1 ] have meant there is increasing interest in recruiting those with higher genetic risk of dementia for investigation of disease mechanisms and targets for prevention and treatment. People from minority ethnic groups tend to be under-represented in dementia trials [ 50 ]. Not only does this mean we have limited understanding of whether treatments are effective in everyone, but it also misses the opportunity to study diverse mechanisms of disease.…”

Preventive drugs for Huntington’s disease: A choice-based conjoint survey of patient preferences

“…Deeper speculation into the differences in perception of preventive treatments between racial and ethnic groups is beyond the scope of this study; however, further research is needed to support racial equity in the HD community and the US healthcare system. By highlighting the importance of this demographic information in HD clinical studies, we can reduce the potential of race-based disparity in clinical trial enrollment observed in other neurodegenerative diseases [48,49].…”