To Recruit for Diverse Alzheimer Trials, Go to the People

Series - Clinical Trials on Alzheimer's Disease (CTAD) 2023 - 16th:

Despite evidence that African American, Hispanic and Latino, and other minority groups have higher rates of Alzheimer’s and related dementias in the U.S., these populations are less likely to take part in clinical studies. This underrepresentation makes it difficult to understand differences in vulnerability to disease among populations, and whether treatments will work the same way in everyone. Stakeholders who grapple with these challenges reported making progress toward overcoming them at a conference called Enhancing Participation by Minoritized Groups in Alzheimer’s Disease and Dementia Research, which was held October 3 to 4 at Washington University School of Medicine in St. Louis. Similar issues resonated in Boston, at the Clinical Trials on Alzheimer's Disease Conference held October 24 to 27.

  • Sustained community engagement needed to recruit underrepresented groups.
  • Some outreach efforts are already working.
  • Differences in AD biomarkers across ethnoracial groups warrant study.

WashU’s Knight Alzheimer’s Disease Research Center hosted the former meeting. Director John Morris said that participants in AD and dementia research studies ought to reflect the populations most affected by these diseases. Not only is this the right thing to do, it’s also good science, he told Alzforum. The meeting drew more than 300 participants in person or virtually, including representatives from each of 37 National Institute on Aging-funded Alzheimer Disease Research Centers (ADRCs).

Consuelo Wilkins, a geriatrician and associate director of the Vanderbilt University’s ADRC in Nashville, Tennessee, argued that the onus of recruiting underrepresented groups falls on researchers. “Often when we think about barriers to participating in research and clinical trials, we put the blame on the people who are not participating,” Wilkins told the audience. “We cannot excuse ourselves from being the solution.”

Solutions, according to the speakers, start with community outreach and trust-building. Researchers noted that teams of outreach specialists familiar with the community at hand can lay the groundwork of connection and trust before potential participants are asked to join a study. Biomarker studies, including ADNI, have started to apply such community engagement methods to attract more Hispanic/Latino and black/African Americans, and reported that these approaches are paying off. (For a summary of biomarker data across ethnoracial groups, see Part 2 of this series.) 

Funded by the National Institute on Aging, this year’s meeting was a follow-up to a prepandemic inaugural that had focused on African American participation (Oct 2018 conference news series). This time, the scope was expanded to consider Hispanic/Latino, Asian, Native Americans, as well as sexual and gender minorities. Inclusion of people with disabilities was also mentioned. Besides showcasing recruitment strategies, the meeting focused on social determinants of health that could contribute to dementia across underrepresented groups, as well as research participation.

Shifting Responsibility
Johnathan Jackson is a cognitive neuroscientist who directs the Community Access, Recruitment, and Engagement (CARE) research center at Massachusetts General Hospital in Boston. He noted that 92 percent of participants in the Phase 3 pivotal TRAILBLAZER-ALZ-2 trial of donanemab, which recruited in 2020 and 2021, were non-Hispanic white. In the Phase 3 CLARITY-AD trial of lecanemab, that number stood at 76 percent, while 12 percent were Hispanic and 2.5 percent black. Owing to Eisai’s recruitment in Japan, 17 percent were Asian. Despite some remaining underrepresentation, especially for black and African American people, Jackson thinks recruitment of diverse populations in ADRD studies is outperforming that in other disease areas. Jackson heads a study called Foundations of Representative Engagement, Valid, and Effective Recruitment. Funded by the NIH, FOREVER is surveying attitudes about research participation in diverse communities at 21 ADRD research sites to learn about knowledge gaps among study staff, and recruitment challenges at each site. The idea is to help scientists engage with the communities they serve, Jackson said.

For her part, Wilkins leads the Recruitment Innovation Center at Vanderbilt, which develops tools to boost participant enrollment and retention in clinical trials. The center works with study leaders from across the country to develop community-based recruitment strategies tailored to each study’s target population. They specialize in equipping researchers with the knowledge and resources to connect with, recruit, and retain participants from underrepresented groups.

One such tool, called Faster Together, is a free, eight-module online course that teaches strategies for recruiting marginalized racial and ethnic groups. More than 4,000 people have enrolled so far, Wilkins said.

Building community partnerships that improve participation requires time and effort. Mark Gluck, Rutgers University, Newark, New Jersey, titled his talk, “There is no quick, easy, or cheap way to recruit older African Americans to aging and brain health research.” Gluck leads the Pathways to Healthy Aging in African Americans study of 500 cognitively healthy black/African American volunteers age 60 and older from the greater Newark area. Enrollees come for yearly, three-day visits of health assessments, cognitive tests, and brain scans.

The study has been ongoing for 17 years, but nine years of work in the community laid the groundwork before study recruitment began. A 16-person community engagement team connected with 40 local churches, 13 public/low-income housing areas, as well as local businesses, medical clinics, and senior centers. The team holds community events, such as dances, fitness classes, even a classic car show aimed at African American men, who are notoriously challenging to recruit, Gluck said. At these events, the scientists share information about the pathways study while also offering other resources of interest, for example information about diabetes or COVID vaccines.

Reinforcing Gluck's message that building trust and partnerships requires time and resources, Raina Croff, of Oregon Health and Sciences University in Portland, urged outreach efforts to address the broad health needs of the community. Croff noted that community outreach and study recruitment tend to get handled by the same staff, arguing that outreach should be distinct from recruitment. This would enable outreach specialists, who ideally have experience in the communities they serve, to interact with the community in a less transactional way. “We need funding to support such positions,” she said.

Morris agreed, adding that community outreach work is not specifically earmarked as part of the recruitment budget in most NIH-funded research studies. Funding for community-based recruitment strategies to spur more diverse ADRD studies is highlighted as a top priority in the NIA’s 2024 budget. Partly pursuant to a 2022 RfA about community-based networks to promote inclusion of underrepresented groups, such funding is increasing.

New IDEAS About Biomarkers
The advent of amyloid-targeted drugs has heightened the urgency behind calls to broaden access to, and ensure the accuracy of, Alzheimer's disease diagnostic biomarkers across populations. In St. Louis, Wilkins showed findings from a secondary analysis of the Imaging Dementia-Amyloid Scanning study. IDEAS asked if amyloid scans improve health outcomes of some 20,000 Medicare recipients with MCI or dementia (Wilkins et al., 2022; Rabinovici et al., 2019). About 90 percent of them were white.

The original study had not broken down the data by race or ethnicity, but when Wilkins and colleagues did so, they found that people who identified as Asian, Hispanic, or black were 53, 32, and 29 percent less likely to have a positive amyloid PET scan, respectively, than were white people. This finding raises questions about differences in the etiology or prevalence of AD across different racial and ethnic groups. It also implies that fewer members of these groups would be eligible for amyloid-targeted therapies, or be likely to benefit from them, Wilkins said. 

To understand these differences, Wilkins co-leads “New IDEAS.” This sequel to the original aims to enroll 7,000 people, including 4,000 who are black/African American or Hispanic/Latino, plus 3,000 from any ethnoracial group, including non-Hispanic whites. As with the first iteration, New IDEAS includes Medicare recipients diagnosed with MCI or dementia, whose physician has referred them to a PET center. Wilkins said this poses a barrier, because fewer people from underrepresented groups are referred for PET, and some lack Medicare coverage or use Medicare Advantage, a form of Medicare many radiology centers do not accept. To remove this barrier, Wilkins and colleagues are securing funding to cover co-pays for PET scans and provide transportation to scanning centers.

To reach the desired groups in the first place, they are rolling out culturally adapted recruitment materials to targeted populations. They also have paused enrolling non-Hispanic white people to focus on minority groups. As a result, minority recruitment is on the rise, with 4,809 enrolled so far, including 1,123 African American and 1,018 Hispanic/Latino people, Wilkins told Alzforum.

Other biomarker studies are following suit. ADNI, the poster child of AD biomarker studies, between 2004 and 2020 screened 3,739 participants, of whom a combined 11 percent were black, Latino, or Asian even though these groups constituted a quarter of the population at the time (Ashford et al., 2022).

To help diversify ADNI, Godfrey Coker, of the Icahn School of Medicine at Mount Sinai in New York, joined the study. In St. Louis Coker described the ADNI Diversity Task Force formed in 2020. The group includes 15 engagement and recruitment specialists and 13 Diversity Recruitment Hub sites. Each site was awarded $150,000, plus the task force offered consultation, community engagement resources, and locally tailored social media campaigns. The task force dropped ADNI’s requirement for lumbar puncture, a procedure minority groups are particularly reticent to undergo. They also agreed that participants could learn their amyloid PET scan result, a common request among all research participants. In return, each site was expected to enroll five to 10 black or Latino participants. A San Francisco-based marketing firm was hired to create targeted Facebook ads and locally tailored ADNI landing pages (image below). The task force also involved local grass roots organizations, Coker said.

Custom Tailored. ADNI landing pages try to attract specific ethnocultural populations [Courtesy of Godfrey Coker, ADNI.]

Is it working? Coker reported that three-quarters of all new ADNI enrollees at participating sites came from underrepresented groups, bumping up the cohort’s overall proportion of non-whites by 20 percent.

The tools are also being used in ADNI4, which is just beginning, Coker said. This round of ADNI aims to screen 30,000 people, including 50 to 60 percent from underserved populations, which Coker said will include people of all ethnoracial groups with lower socioeconomic status and less education than the average ADNI participant.

Sid O’Bryant, of the University of North Texas in Fort Worth, considers less than 50 percent underserved groups inadequate for any ADRD study these days. Aiming higher will require changes to how clinical studies recruit, O’Bryant said. “We stay in our clinics, ignoring the research documenting that people from underserved communities do not present to specialty clinics,” O’Bryant said. To his mind, solving this problem boils down to this: “We need to meet the community where they’re at.”  

O’Bryant works predominantly with Hispanic/Latino and black/African American people in the Dallas-Fort Worth area. He told Alzforum that going to the community works for any population not typically seen in a specialty clinic, including non-Hispanic whites who don’t fit the more highly educated, wealthier profile of the average memory clinic patient.

As the leader of the Institute for Translational Research at UNT, formed with an NIH grant in 2018, O’Bryant and his team frequently visit local churches, bingo games, community centers, and people’s homes, focusing on Hispanic/Latino and African Americans. To build the trust and partnerships that underpin study participation, O’Bryant said his team approaches a community not by asking them to join; instead, they first ask about needs and concerns, listen, and then try to serve each community’s needs. As does ADNI, O'Bryant lets participants see their data, including MRI and PET scans and cognitive test results.

O’Bryant’s team has used this approach to recruit participants in the Health & Aging Brain Study-Health Disparities (HABS-HD). Like ADNI, this multicenter, longitudinal study collects imaging, fluid biomarker, cognitive, and other health data on its participants. Unlike ADNI, HABS-HD was originally designed with community engagement recruiting to draw non-white participants. The study aims to recruit 1,500 Hispanic/Latino, 1,500 black/African American, and 1,500 non-Hispanic white participants. So far, 1,600 Hispanic, 1,000 African American, and 1,300 whites are on board. This success shows the power of community-based approaches, O’Bryant said.

A recording of this conference is available on the Knight ADRC’s YouTube page: https://www.youtube.com/playlist?list=PLGr7La2kVfSY7u-3MKPX61Rq_q5hOIwNn.

In St. Louis, O’Bryant presented initial data on stark differences between amyloid PET positivity, and other AD biomarkers, across racial and ethnic groups. Researchers at CTAD did as well. For the highlights of these biomarker findings from both meetings, see Part 2 of this series.—Jessica Shugart

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References

News Citations

  1. From St. Louis to Boston, Scientists Grapple with Ethnoracial Divide in AD Biomarkers
  2. Alzheimer’s Researchers Seek Advice on How to Include African-Americans

Paper Citations

  1. Wilkins CH, Windon CC, Dilworth-Anderson P, Romanoff J, Gatsonis C, Hanna L, Apgar C, Gareen IF, Hill CV, Hillner BE, March A, Siegel BA, Whitmer RA, Carrillo MC, Rabinovici GD. Racial and Ethnic Differences in Amyloid PET Positivity in Individuals With Mild Cognitive Impairment or Dementia: A Secondary Analysis of the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) Cohort Study. JAMA Neurol. 2022 Oct 3;79(11):1139-47. PubMed.
  2. Rabinovici GD, Gatsonis C, Apgar C, Chaudhary K, Gareen I, Hanna L, Hendrix J, Hillner BE, Olson C, Lesman-Segev OH, Romanoff J, Siegel BA, Whitmer RA, Carrillo MC. Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia. JAMA. 2019 Apr 2;321(13):1286-1294. PubMed.
  3. Ashford MT, Raman R, Miller G, Donohue MC, Okonkwo OC, Mindt MR, Nosheny RL, Coker GA, Petersen RC, Aisen PS, Weiner MW, Alzheimer's Disease Neuroimaging Initiative. Screening and enrollment of underrepresented ethnocultural and educational populations in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Alzheimers Dement. 2022 Feb 25; PubMed.

External Citations

  1. NIA’s 2024 budge
  2. https://www.youtube.com/playlist?list=PLGr7La2kVfSY7u-3MKPX61Rq_q5hOIwNn

Further Reading

Papers

  1. Lewis A, Gupta A, Oh I, Schindler SE, Ghoshal N, Abrams Z, Foraker R, Snider BJ, Morris JC, Balls-Berry J, Gupta M, Payne PR, Lai AM. Association Between Socioeconomic Factors, Race, and Use of a Specialty Memory Clinic. Neurology. 2023 Oct 3;101(14):e1424-e1433. Epub 2023 Aug 2 PubMed.
  2. Gleason CE, Zuelsdorff M, Gooding DC, Kind AJ, Johnson AL, James TT, Lambrou NH, Wyman MF, Ketchum FB, Gee A, Johnson SC, Bendlin BB, Zetterberg H. Alzheimer's disease biomarkers in Black and non-Hispanic White cohorts: A contextualized review of the evidence. Alzheimers Dement. 2021 Dec 6; PubMed.

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