Minorities Knocked Out of AD Trials at First Screening

Blacks and Hispanics were often labeled ineligible early in the screening process for preclinical trials for Alzheimer’s disease (AD), despite carrying a higher disease risk and burden, researchers reported.

In an analysis of screening data from the Anti-Amyloid in Asymptomatic AD (A4) study, Black (odds ratio 0.43, 95% CI 0.34-0.54, P<0.001) and Hispanic (OR 0.53, 95% CI 0.41-0.69, P<0.001) people, as well as Asian people (OR 0.56, 95% CI 0.38-0.82, P=0.003), were less likely to be eligible after the first screening visit versus White participants, according to Rema Raman, PhD, of the University of Southern California Alzheimer’s Therapeutic Research Institute in San Diego, and co-authors.

In the 5,945-participant study, Blacks were “more frequently excluded for failure to meet cognitive inclusion criteria (e.g., screen failures by specific inclusion criteria),” versus White participants at 45.5% versus 26.2%, they wrote in JAMA Network Open.

Yet, the “risk and burden of AD are greater among African American/Black and Hispanic/Latino individuals compared with non-Hispanic White individuals,” Raman’s group noted. But “Preclinical AD trials face difficultly in recruiting diverse participants, perhaps in part due to unique challenges in these novel studies,” such as difficulty in obtaining biomarker status for preclinical AD trials, which rely on “evidence of AD biology on biomarker tests in the absence of cognitive impairment.”

The ongoing, multisite A4 study of solanezumab in older adults with preclinical AD categorized participants into five mutually exclusive racial or ethnic groups: Hispanic, Black, White, Asian, or other, with participants self-reporting ethnic or racial status.

And therein lies part of the problem, pointed out Jennifer J. Manly, PhD, of Columbia University Irving Medical Center in New York City, and co-authors, in an invited commentary accompanying the study. The current findings “reveal that—as is often the case—prospective participants who were White, well-educated, and well-resourced were centered at each step of the design and execution process of the A4 trial.”

For instance, the authors showed that potential minority participants were more likely to be recruited through community outreach or through referrals, while White participants were more likely to targeted through “earned media,” such as news coverage, or paid media, such as online ads. It was not known if similar media-based outreach was done for minority communities, and what the duration and intensity of that outreach was, according to Manly and co-authors.

They confirmed that Clinical Dementia Rating scores >0 and low Mini-Mental State Examination and Logical Memory scores “were the primary reason for excluding participants from minoritized racial and ethnic groups at the initial screening” (63.6% of exclusions, per Raman’s group). However, “without data on people who were screened out, we cannot determine whether racial and ethnic differences in the initial screening were the product of well-documented measurement biases in neuropsychological measures, population differences in burden of cognitive impairment, or group variation in amyloid burden,” Manly’s group wrote.

Manly and co-authors called it a “worthy exercise to question the ways these practices do and do not facilitate participation in some groups,” but said more emphasis was needed on determining “why the systems and structures of recruitment are so commonly designed around White, resourced populations as a prioritized, referent norm.”

Those in the screening cohort for the current study had a mean age of 71.7, with women making up 59.3% of the population; 85.9% were White, while 5.4% were Black, 4.4% were Hispanic, 1.9% were Asian, and 2.4% were other.

The primary outcomes of the analysis were recruitment sources, study eligibility, and ineligibility reason. Case report forms that captured recruitment data at participant enrollment were available for 97.8% of the cohort.

Raman’s group reported that site recruitment efforts were the primary source for Black (69.2%), Hispanic (59.7%), and Asian (55.5%) participants, followed by local earned media. In comparison, White participants were recruited by “more distributed sources,” including site recruitment efforts (42.5%), local earned media (21.9%), national earned media (16.5%), and trusted organizations (11.5%).

They also looked at the frequency of screen failure across cognitive criteria, and found that the frequencies of exclusion were 26.1% for Hispanics, 30.7% for Blacks, 26.8% for Asians, and 16.2% for Whites.

“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,” Raman and coauthors suggested.

Study limitations included the fact that data on recruitment sources were limited to forced-choice options that may not have perfectly accounted for the type or amount of effort required for participant recruitment. Also sample bias may have been exacerbated by the relatively small sample sizes in the study, “despite that they are among the largest samples of Black, Hispanic, and Asian participants in AD clinical trials,” the authors wrote.

They offered 10-point “actionable recommendations” to improve recruitment and enrollment of minorities in preclinical AD trials, while other researchers have proposed strategies, such as intervention mapping and peer-driven recruitment, to boost inclusion of minorities into clinical trials in general.

1. Black and Hispanic people, as well as Asian people, were less likely to be eligible after the first screening visit versus White participants in an analysis of screening data from the Anti-Amyloid in Asymptomatic AD (A4) study.

2. Potential minority participants were more likely to be recruited through community outreach or through referrals, while White participants were more likely to targeted through “earned media,” such as news coverage, or paid media, such as online ads.

Shalmali Pal, Contributing Writer, BreakingMED™

Cat ID: 33

Topic ID: 82,33,282,585,485,730,33,192,255,148,925