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    Clinical trials seek to fix their lack of racial mix

    Most drugs have been tested primarily on White men, casting doubt about their efficacy for others. Researchers are trying to diversify who participates in studies.

    A diverse doctor and patient talk in an exam room

    When the biotechnology company Genentech convened a summit of patients four years ago to discuss the value of their participation in clinical trials, it came up empty for one group of people.

    “We could not find one patient of color that had participated in our research to be able to speak at this summit,” recalls Quita Beeler Highsmith, MBA, who was then working on patient alliances and advocacy relations at Genentech, headquartered in South San Francisco. She wondered why and discovered that few Black patients had participated in the trial, which is typical. Black patients account for just 5% of clinical trial participants in the United States, while White patients make up the vast majority.

    Genentech set out to recruit more people from underrepresented populations into its trials, including one last year to test a COVID-19 pneumonia treatment in patients from underserved communities in the United States and overseas. Among the 389 participants in the Evaluating Minority Patients with Actemra (EMPACTA) study, approximately 84% were from Black, Hispanic, Native American, and other historically underrepresented groups, says Highsmith, now Genentech’s vice president and chief diversity officer.

    That study is one example of how hospitals, medical schools, and medical product developers are intentionally seeking ways to increase demographic diversity in clinical trials for everything from vaccines to therapeutic drugs to devices. Research leaders believe the fact that those products have traditionally been tested primarily on White people — especially young and middle-aged men of European decent — creates blind spots about the effectiveness of the treatments among some populations and leaves some people in those populations distrustful of the products.

    “We're not all the same physiologically,” notes Clyde Yancy, MD, vice dean for diversity and inclusion at Northwestern University Feinberg School of Medicine in Chicago. “Whether it's because of age or illnesses or genetic ancestry, we likely all metabolize drugs differently; we may respond to devices differently.”

    The underrepresentation problem has vexed researchers for years, but the remedies have focused primarily on trying to fix perceptions about clinical trials among minority populations rather than changing how trials are designed and carried out.

    “We bemoan the fact that we can’t recruit a certain population,” Yancy says. “We ask, ‘Why are they so recalcitrant to participate?’ It’s because we're recalcitrant to make the kinds of changes that would fundamentally reinvent how we do clinical trials.”

    Some researchers have started instituting such changes, including bringing trial procedures closer to where participants live, diversifying the staff who recruit people for the studies, and designing trials to directly target underrepresented groups.

    Bring trials into communities

    One of the biggest barriers to participating in a clinical trial is getting there. The typical trial requires patients to repeatedly travel to a central site — such as a university hospital — for assessments, administration of therapies, tests to monitor results, and medications to take at home. This often involves several hours per trip as well as paying for transportation and food. These requirements create a selection bias by eliminating many people with little disposable income, few transportation options, inflexible work hours, and family-care obligations, explains Jonathan Jackson, PhD, executive director of the Community Access, Recruitment and Engagement (CARE) Research Center at Massachusetts General Hospital in Boston. Relatively affluent, white-collar patients are often most likely to have the time and other resources to participate.

    One way to remove that bias is to carry out at least some of the procedures at hospitals, clinics, and doctors’ offices in communities where minority populations live. “There’s no need to spend two hours getting to an academic medical center for a 45-minute basic assessment,” he says.

    At the University of Alabama (UAB) School of Medicine, the O’Neal Comprehensive Cancer Center eases the travel burden by teaming with local oncology clinics and other medical facilities throughout the state to conduct such procedures as routine check-ups and the administration of medicines so that patients in trials don’t have to come there so often. “If we get someone from far south in the state, that could be a four-hour drive each way,” notes Monica Baskin, PhD, associate director for community outreach and engagement.

    Genentech’s EMPACTA study went a step further: The trials were based in facilities that serve underrepresented populations, including Larkin Community Hospital in South Miami, Florida; Highland Hospital in Oakland, California; and Harlem Hospital Center in New York. Genentech provided training, resources, and monitoring for staff at those facilities to implement the trial, according to Highsmith.

    “People want to go to facilities that are in the neighborhood,” she says. Not only is that convenient, she observes, but people are also more likely to have a trusted relationship with local caregiving institutions than with distant research centers.

    Reflect the population being recruited

    When people from underrepresented populations are approached about participating in a clinical trial, they usually do not see themselves in the face of the person explaining the trial. The explanation typically comes from a trial investigator or staff member — most of whom are White men with advanced college degrees who are living middle- to upper-class lives in metropolitan areas. That can make it difficult for people from other backgrounds — including members of minority groups and people with low incomes, without graduate degrees, and from rural areas — to feel that the recruiters understand the circumstances of their lives.

    “What happens if we change the trials so that the persons that are involved [in running them] look like and think like the patient groups that are typically not involved?” Yancy ponders.

    That’s one strategy used by the CARE Research Center, which runs trials and consults on expanding diversity in trials run by other organizations. The center advises research organizers to intentionally diversify the staff working on studies — especially those who interact most often with potential participants.

    “If you have diversity in your patient-facing staff, that is where you will see immediate results,” says Jackson, the center’s executive director.

    The O’Neal Center at UAB takes that approach by supplementing the recruitment efforts of the study staff. The center recruits people in communities throughout Alabama to serve as “lay community navigators” who educate local people about health issues and link them to services and resources at the center, including clinical trials. The center trains the navigators to explain the trials, connect people to the process to consider enrolling, and help them with logistics such as transportation and lodging if they do enroll, Baskin explains.

    She notes that it’s “really important” that prospective participants see the navigators as peers in terms of race, life experiences, or the communities where they live. “It’s a matter of finding that way to connect with them that opens the door,” she says.

    Change trial designs

    Efforts to increase diversity must begin long before a trial gets underway — that is, with the design of the study itself, according to research leaders.

    For example, Yancy says that study designs should include numerical targets for enrolling people from underrepresented groups, especially those who might benefit from the treatment being studied because of the prevalence of a disease in those groups. 

    “That kind of intentionality has to start on the front end,” he notes. “You bake it into the recipe. That way you make sure you’ve incorporated a way to be more inclusive, and you execute a trial with more relevant answers.”

    In addition, Highsmith says that study designers can broaden the eligibility criteria for trials and reduce the criteria that exclude people. She observes that many study authors use exclusion criteria — typically for conditions such as a certain body mass index or white blood cell count — that were used in similar studies, but the researchers don’t always consider the potential unintended impacts of the restrictions and whether they’re necessary for the study.

    “So even if you have a disease and want to participate in a study, the exclusion criteria will kick you out,” explains Highsmith, whose company has revised its eligibility criteria.

    Federal agencies that fund trials have taken up these ideas, to a point. The National Institutes of Health requires grant applications for trials to include plans for recruiting women and members of minority groups. The Food and Drug Administration issued guidance in November 2020 that includes broadening eligibility criteria, avoiding “unnecessary” exclusions, and improving recruitment so that participants “will better reflect the population most likely to use the drug.” 

    Yancy says that government and private funders must go beyond guidance and issue requirements for recruitment targets, with those that succeed being rewarded with more funds or grant opportunities.

    Challenge assumptions

    Beyond changing policies and practices, the diversification efforts aim to change something larger: the assumption that some groups are significantly underrepresented in trials because they don’t want to participate. That assumption creates a self-fulfilling prophecy, as researchers don’t try new ways to reach those populations and doctors don’t talk to certain patients who might be eligible for trials that could treat their ailments.

    “When we’ve studied this” assumption by asking people from underrepresented groups why they don’t participate in trials, Baskin reports, “they say, ‘I was never approached.’”

    That’s why the O’Neal Center is developing a package of educational materials for caregivers in the UAB health care system to explain how trials work, the importance of diversifying participation, and how to talk with patients about trials that might benefit them.

    While most of the diversification efforts are too new to demonstrate results, people working on the initiatives say that confronting the issue head-on will pay off. 

    “The thing that makes me happy,” Highsmith says, “is that we’re no longer tiptoeing around the issue of race.”