Article
Racial and Ethnic Disparities Identified in AD Clinical Trial Enrollment
Author(s):
Investigators found that certain underrepresented communities were less likely to be eligible for Alzheimer disease trials after the first screening visit.
Rema Raman, PhD
A cross-sectional study of screening data for an Alzheimer disease (AD) preclinical trial showed difference in sources of recruitment, reasons for screen failure, and general eligibility amongst racial and ethnic groups, ultimately leading to a smaller portion of non-White individuals meeting eligibility criteria. Minimizing these disparities and improving recruitment strategics is crucial, as a lack representation from minoritized AD groups limits the ability to generalize results and examine treatment effects on different candidates.
Data was analyzed from the Anti-Amyloid Asymptomatic AD study, spanning April 2014 to December 2017, evaluating an anti-Aβ monoclonal antibody in older adults with preclinical AD. Of the 5945 participants screened, all were cognitively unimpaired older adults. Participants self-reported ethnicity/race and were subsequently categorized into 5 mutually exclusive groups (Hispanic, Black, White, Asian, and other). The mean age was 71.7 years (standard deviation, 4.9), with a total of 3524 women (59.3%), and 5107 identifying as White (85.9%), 323 (5.4%) as Black; 261 (4.4%) as Hispanic; 112 (1.9%) as Asian, and 142 (2.4%) reporting as other.
Participants from underrepresented groups had lower mean years of education compared to White participants, were more frequently women, unmarried, and had nonspousal partners. Those identifying as part of underrepresented groups were more frequently excluded for failure to meet cognitive inclusion criteria, such as screen failures by specific inclusion criteria, as seen with 147 (45.5%) of Black participants being excluded versus 1338 (26.2%) of White participants. Black (odds ratio [OR], 0.43 [95% CI, 0.34-0.54]; P <.001), Hispanic (OR, 0.53; 95% CI, 0.41-0.69; P <.001), and Asian participants (OR, 0.56; 95% CI, 0.38-0.82; P = .003) were less likely to be eligible after screening visit 1 (ScV1).
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Recruitment sources varied amongst ethnicities and races, and local site efforts such as other studies, community outreach, internal clinic or site physician referrals were found to be the most frequent sources for Black (n = 218 [69.2%]), Hispanic (n = 154 [59.7%]), and Asian (n = 61 [55.5%]) participants. Most White participants, however, were recruited through earned media.
“The current results suggest that, even among the relatively small number of Hispanic and non-White participants recruited to the A4 trial, participants differed in their recruitment sources, their demographic and clinical characteristics, the reasons that they were excluded from participation, and their overall likelihood of being eligible for randomization,” lead author Rema Raman, PhD, et al wrote. “To the extent that the A4 Study is an accurate model of recruitment results for future preclinical AD trials, addressing each of these elements may be necessary to conduct truly inclusive studies of representative and generalizable samples.”
The screening process for selection took place over 5 visits within 90 days. Participants were excluded in the events of serious illness, significant laboratory abnormality, significant electrocardiogram, as well as contraindications for magnetic resonance imaging studies. At the ScV1, Hispanic and non-White participants were less likely to be eligible, most frequently due to Clinical Dementia Rating (352 screen failures [20.9%]) and Logical Memory II scores (718 screen failures [42.7%]).
“Ensuring positive experiences of participants who overcome barriers to participation and enroll in studies may be essential to gaining and maintaining trust among underrepresented communities. The experience of enrolling in a trial only to be excluded based on eligibility criteria is often interpreted as rejection or being unwanted,” the authors wrote.
Several limitations were identified, such as the limited data collected from recruitment sources. This included demographics of different site locations, staff demographics and effort, as well as how allocated expenditures were used for study advertisements.
“We observed an alarmingly lower likelihood of eligibility among Black, Hispanic, and Asian participants compared with White participants,” investigators wrote. “Eligibility criteria must be carefully selected to balance competing objectives of protecting participants from unnecessary risk, enroll individuals who are most likely to benefit from the study treatment, and produce research results that are generalizable to the larger population intended for treatment.”
Further studies are necessitated to look into how sociocultural factors impact trial eligibility, namely literacy, socioeconomic status, beliefs and attitudes about dementia, among others. In doing so, diversity may become more prevalent in clinical research.
