Article In Brief
Investigators discuss the challenges and opportunities of recruiting more diverse groups in neurology research.
As the discovery of biomarkers and new therapies for neurological disease continues to grow, the significant gaps in the representation of diverse populations in clinical trials have become all the more apparent. This problem is particularly alarming in conditions for which minority populations are at higher risk or experience significantly greater mortality rates, such as Alzheimer's disease (AD), multiple sclerosis (MS), and stroke.
In an editorial published online in the January 3 issue of CNS Spectrums, Jagannadha Avasarala, MD, PhD, professor of neurology at University of Kentucky Medical Center in Lexington, KY, wrote about the paucity of data for US Food and Drug Administration (FDA) approved drugs for MS in non-white patients, and emphasized the need for change.
This disparity is “troublesome,” he said, adding that some of the onus should fall to the drug companies who need to publicly acknowledge this absence of data. “What might change the outlook in minority communities is simply the acknowledgment by the drug companies (sponsors of studies) and the authors who write up these studies and publish them that data simply do not exist in minorities owing to lack of recruitment numbers. Then, hopefully, and ever so slowly, community leaders or concerned citizens might get out there and enroll themselves in studies.”
For one thing, he suggested journals might consider only accepting publications if they reach a set recruitment figure or, if that isn't possible, to at least acknowledge their inability to make “global and sweeping conclusions” due to low numbers. Regardless of why the disparities in data exist, he said, “the final effect is the same and every under-represented community eventually loses.”
Of course, the lack of diverse patient data is not unique to MS—or neurology for that matter—but it is an increasingly visible challenge that leaders in the field are working to address. Neurology Today spoke to several investigators involved in clinical research about how they are addressing patient recruitment and retention gaps, as well as the substantial barriers that stand in the way.
Some of those barriers are rooted in the historical legacy of ethical lapses in the conduct of clinical trials, investigators told Neurology Today—cases, for example, that include the Tuskegee study, which ran from 1932-1972, without the informed consent of the black male participants who went untreated for syphilis.
“The scientific field has a sordid past when it comes to research with these [minority] populations,” said Lisa L. Barnes, PhD, the Alla V. and Solomon Jesmer professor of gerontology and geriatric medicine at Rush Alzheimer's Disease Center. “It takes significant effort to educate people about how research ethics have changed over time, and to be as transparent as possible in communicating the reasons for the research.”
Efforts are underway to do just that. On a national level, the National Institute of Neurological Disorders and Stroke (NINDS) has made diversity in research a focal point for a program called Focus on Health Disparities Research aimed at “reducing the disproportionate burden of neurological disease borne by underserved groups of society, including racial and ethnic minority, rural, and socioeconomically disadvantaged populations.” The program aims to increase funding for the study and training for investigators in the health disparities field.
Dr. Avasarala also noted efforts by the FDA, which created the Drug Trials Snapshots initiative that allows consumers to look at demographic data from clinical trials and highlights any differences in the benefits and side effects among sex, race, and age groups.
Diverse study populations are vital to understanding how different patient groups respond to the same treatments, as well as the varied courses the disease itself may take in different groups. Recently, John C. Morris, MD, FAAN, Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology and director of the Knight Alzheimer's Disease Research Center in St. Louis, and colleagues published a paper in the January 7 online edition of JAMA Neurology, which found racial differences in Alzheimer biomarkers that suggest “possible race-dependent biological mechanisms that contribute to expression of disease.”
The reason Dr. Morris and fellow investigators were able to make this discovery at all, he said, dates back to nearly two decades of outreach efforts to the diverse population in the area of the medical center. When Dr. Morris first came to the Knight Center in 2000, he recognized that the center's research volunteers were overwhelmingly white and not representative of the city's population. To help engage with the community and recruit more diverse volunteers, Dr. Morris established an African-American advisory board made up of leaders from the community.
More than half of the advisory board members, Dr. Morris said, are research volunteers in the Knight Center as well, so when they reached out to their family, friends, and acquaintances, they were speaking from personal experience. “Our advisory board [comprising African-American leaders from the community] have been very helpful demonstrating that we are trustworthy—and that's no small challenge. Missouri, like many border states, has a long history of discriminatory practices against African-Americans,” he said. Older adults, he added, certainly remember this legacy firsthand.
It has taken decades, but the research population at their medical center is now 18 percent African-American, he said, which is representative of the population in the catchment area.
This increase in African-American representation enabled Dr. Morris and colleagues to discover that although amyloid profiles were identical for African-American and white patients, the levels of tau for African-Americans were always substantially lower—a difference that will now need to be studied further and could have important clinical implications.
Plan Ahead, Involve the Community
In study sites where the local population is already more diverse, researchers may have an easier recruitment pipeline for minority populations as long as they plan ahead, said Virginia Howard, PhD, professor in the department of epidemiology at the University of Alabama School of Public Health and a co-principal investigator on the REasons for Geographic and Racial Differences in Stroke (REGARDS) study and many completed stroke clinical trials. Dr. Howard is also a co-investigator on the ongoing CREST2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis) trial, which is working to increase enrollment of different racial-ethnic groups.
Dr. Howard stressed that better advanced planning by investigators and coordinators could make a major difference in recruitment. “Ideally you want to get some statistics on the prevalence of the specific condition you are studying in different ethnic groups.” She pointed out that unfortunately there aren't usually great data on this, but you can reach out to the individual hospitals or clinics you might be recruiting from for a multi-site trial and use that information to carefully select sites based on their referral populations.
“In a particular city, for example, you may have five or six hospitals, but their referral patterns are different and may favor different communities,” Dr. Howard said.
She suggested running focus groups or working with disease-specific patient advisory groups to find out the best way to design the study protocol and address any potential hurdles to participation. For instance, she noted that investigators should carefully consider their exclusion criteria as being as parsimonious as possible and related to potential harm and potential ineffectiveness of the interventions being tested.
Mitchell S.V. Elkind, MD, FAAN, professor of neurology and epidemiology in the Gertrude H. Sergievsky Center at Columbia University, who is a co-investigator on the Northern Manhattan Study, said that they have a highly diverse population at their medical center, which already includes a large proportion of Hispanics and African-Americans. “The medical center is well-respected in the community, and employs many people from the community, so that it has a good reputation among community members.” He noted that they make an effort to communicate with local physicians and work closely with the local community board.
Dr. Elkind and colleagues also attend local meetings to explain their studies, and their medical center holds community outreach days, during which study investigators present their findings to the community. They translate all materials into Spanish to meet the needs of their population.
Dr. Barnes, who wrote an editorial in response to Dr. Morris' study in the same issue of JAMA Neurology, highlighted this critical need to communicate study results to the population, so they don't feel like guinea pigs, “a concept that still floats throughout the minority community,” she said.
Hiring more people of color as research personnel and staff “so it's not all white people in white coats” is essential as well, Dr. Morris added, as is asking the community what research questions they care about most, rather than deciding for them. In Dr. Barnes' experience with observational longitudinal studies, involving the community has been the most successful step, though she acknowledged that these same methods wouldn't necessarily translate to clinical trials which require more commitment from patients.
“In our research,” Dr. Barnes said, “we apply a community-based participatory approach. We follow specific steps to network with community stakeholders, give first to underrepresented communities, advocate for research by explaining why the work is needed and how it will help the community, give back to those communities once we have the results, and constantly evaluate our approach working with the community, to ensure that what we are doing is working for everyone—not just for the researchers.
“It's labor intensive but really effective in building relationships and increasing trust. We have used this approach for over two decades in our studies and currently follow more than 1,000 racially and ethnically diverse people in our various cohort studies,” she said.
A Call to Action
The National Institutes of Health is actively interested in addressing and understanding the reasons for poor recruitment of under-represented communities, Dr. Barnes said. Those reasons will likely extend beyond the lack of trust in researchers, she added, but for now, “the solution is likely multifactorial.” It will require, at minimum, a community-based participatory approach in which researchers and communities work together.
Dr. Morris said his recent study “underscores the fact that almost all the information that we've learned about AD in general and particularly about biomarkers and effects of experimental therapies have been conducted in samples that are almost entirely white.”
We have to do a better job as a field, he continued, at recruiting and retaining members of underrepresented groups to find out whether or not there are racial differences based on biology or other factors such as socioeconomic status, or perhaps even the stress brought on by lifelong discrimination.
“The call is that to really understand Alzheimer's disease or any illness that we are studying, it should be examined in diverse research populations, not simply one dominated by one racial group,” Dr. Morris said.
Drs. Avasarala and Barnes have no relevant disclosures. Dr. Howard receives funding from NINDS as part of an ongoing clinical trial (CREST2). Dr. Morris is a member of the AAN Board of Directors and has received research support from Eli Lilly/Avid Radiopharmaceuticals for studies of Alzheimer's disease and grants from the National Institute on Aging.