Increasing minority representation in lupus trials proves as multifactorial as its barriers


An estimated 1.5 million people living the United States have lupus, and at least 5 million people across the globe have the condition. The disease is more common among people of African American and Hispanic descent. Members of these communities are two to three times more likely to have and die from lupus than their non-Hispanic white counterparts. Moreover, while women overall comprise 90% of the lupus population, black women are three times more likely to develop lupus than white women and they tend to have more severe symptoms and often experience earlier disease onset.


Despite these statistics, the average enrollee in a lupus clinical trial is white – an irony that compromises the relevance and translation of clinical research to minority communities. Ameliorating the barriers requires the medical community first to understand the reasons for the bias in order to devise effective strategies to calibrate study designs that more realistically reflect the target population.

“Minority populations often face multiple barriers to health and health care access that make them harder to be reached,” said Cristina Drenkard, MD, PhD, associate professor of rheumatology at Emory University, Atlanta. “Because these populations tend to be more distrustful of both the research and health care systems, successful recruitment requires a substantial investment of resources and time – which is not always considered or supported by the trials.”


Dr. Cristina Drenkard

Barriers to representation in clinical trials 

There are numerous reasons for the paucity of black and Hispanic patients in lupus clinical trials, experts said in interviews. Perhaps the most poignant of these is how profoundly provider bias impacts minority enrollment, according to Saira Sheikh, MD, director of the clinical trials program at the University of North Carolina Thurston Arthritis Research Center in Chapel Hill.

“The when, where, and how of clinical trials conversation between patients and providers is critically important,” said Dr. Sheikh. “We know the majority of patients who participate in a clinical trial learn about it from their provider.”

Dr. Saira Sheikh

Even when provider-patient conversations occur, many patients subsequently find themselves lost in a sea of medical jargon. The 2009 National Assessment of Adult Literacy found that 36% of U.S. residents have nominal or poor health literacy. This percentage includes the geriatric community, people of low socioeconomic status, and the medically underserved, as well as people of color. Dr. Sheikh described the language barriers patients of color encounter with signs, directions, and paperwork as “overwhelming.”

“These factors can be stressful and confusing for anyone, and from the patients’ perspective, this often feels like an overload of information,” she said. “So often, there are missed or inadequate opportunities to discuss clinical trials.”

Additionally, some Spanish-speaking patients may feel reluctant to participate in clinical trials, fearing their involvement might affect their immigration status.

Color bias highlights clinicians’ misconceptions

Irene Blanco, MD, MS, associate professor of medicine and associate diversity enhancement at Albert Einstein College of Medicine, New York, stated that the perceptions some clinicians may carry may negatively impact minority enrollment and participation.

“There is a lot of color bias with regards to patients of color in clinical trials,” said Dr. Blanco.

Some providers may think: Are they going to be “compliant?” Are they going to “understand?” It’s costly to translate the forms and recruit patients who are of limited English proficiency.

“These ideas can lead to a ‘why bother?’ attitude,” Dr. Blanco said.

The environment in which minorities live may further compound their barriers. Many live in neighborhoods lacking proximity to a hospital where a clinical trial is being conducted.

“Many of these populations are served by community and rural health centers that do not have a research infrastructure themselves to conduct clinical trials,” she said.

Dr. Irene Blanco

The consequences of geopolitics and historical systemic disenfranchisement on underrepresentation

Some of the iniquities regarding the color bias in clinical trials may reflect political and socioeconomic systems that have historically marginalized people of color and continue to do so.

"The U.S. has a well-known history of nonethical and criminal behavior at worst and questionable behavior at best involving communities of color and clinical trials," Dr. Blanco said. "The Tuskegee experiment was suspended in 1973 only after a major scandal."

The 40-year-long Tuskegee experiment is just one of many events that have illustrated a painful history of disenfranchisement of people of color, nearly a century after the experiment’s inception.

Dr. Blanco also cited medical mistrust in the Hispanic community as a consequence of the Puerto Rico Pill trials. In 1956, poor Puerto Rican women who were given oral contraceptives were told the pills were for pregnancy but not that they were part of a clinical trial. Moreover, no studies were conducted to investigate the circumstances under which three women died during the study.

In another example that generated mistrust of the medical community, in 1989, 650 members of the Havasupai Native American tribe in Arizona donated their blood, believing researchers were studying it to help identify risk factors for diabetes. Instead, scientists used their blood samples to evaluate the effects of inbreeding, alcoholism, and the group's Asian migratory origins – all without informed consent.

Doctor drawing blood from a patient as part of the Tuskegee Syphilis Study, 1932.

Multiple efforts underway to increase representation

Past injustices have undoubtedly provided valuable lessons to inform the path to a more ethical, diverse future in medical research. Several initiatives are underway to help enroll more people of color into trials.

For example, Dr. Drenkard studies how individual and psychosocial factors impact racial disparities in lupus patients’ outcomes. Social determinants such as economic stability, education, neighborhood and environment, health and health care system, social and community context, and interpersonal relationships all contribute to racial disparities that prevail in lupus outcomes.

"The social determinants of health and chronic care frameworks help [us to] understand the complex issues involved in low participation of minorities in research," Dr. Drenkard said. "As there are multiple and interconnected issues, a multilevel approach is needed to create a framework that may orient strategies to increase the representation of minorities in research.”

Establishing such a framework means engaging policy makers, providers, scientists, community leaders, patients, lupus organizations, pharmaceutical companies, and funding institutions.

In 2018, the Department of Health & Health Services’ Office of Minority Health awarded 2-year grants  to four institutions totaling nearly $1.75 million to eliminate health disparities plaguing minorities and other disadvantaged groups.

The American College of Rheumatology was among the recipients, receiving funds to increase minority representation in clinical trials for lupus. The result is a partnership between the college’s collaborative initiatives department and ACR member-experts on two projects: the Material to Increase Minority Involvement in Clinical Trials (MIMICT) and the Community Health Worker Lupus Clinical Trials Training.

The program will expand and adapt the ACR's current MIMICT model to ensure that medical information is disseminated to people who have lupus in a more digestible manner to help them make informed decisions about clinical trials. In addition to educational efforts, the initiative includes targeted outreach to rheumatologists and other lupus providers such as primary care physicians and subspecialists such as nephrologists and dermatologists, and as well as allied health care professionals who care for lupus patients.


“My practice is devoted to the care of a large cohort of patients with lupus, a significant percentage of whom are ethnic or racial minorities,” she said.

Dr. Sheikh’s clinic at the University of North Carolina implemented what she calls a “universal precautions” approach to clinical trials, which entails educating and speaking to all patients at the lupus clinic about clinical trials. Engaging in this practice eliminates implicit biases.

The program has additional robust communication protocols in place. The clinic focuses on education, informed decision-making, and open-ended conversation. Researchers enacted a multi-step information consent process that includes snail mail and email copies of consent forms and follow-up phone calls, as well as conversations before the actual informed consent is conducted in person.

Dr. Blanco believes community health workers (CHWs) have untapped potential for improving minority enrollment – the main objective of her collaboration with the ACR. She is developing curricula on clinical trials for CHWs to facilitate their ability to explain clinical trials to interested participants and guide them through the process.

“I think the key is that CHWs come from the communities they work in,” she said. “There’s a certain level of trust and understanding that may not exist from the get-go between the community and investigators – particularly because too often investigators and clinical trial personnel are not of the communities they are trying to recruit.”

Change may not occur overnight, but these efforts are bound to alter the design of future studies for lupus and potentially influence the layout of clinical trials for other diseases where racial and ethnic disparities also abound.