National Academies report cites ‘urgent’ need to recruit more diverse participants for clinical trials

The persistent lack of diversity among participants in clinical trials is a critical issue that is harming both populations that have long been left out of pivotal medical studies and the entire biomedical research enterprise, according to the authors of a report released Tuesday by the National Academies of Sciences, Engineering and Medicine.

Describing the need to move away from trials that focus largely on white men as “urgent,” the report’s authors called for a paradigm shift that gives less power to institutions that fund and conduct clinical research and more to communities under study. The sternly worded report said funding to include and recruit more diverse participants should be a priority that is enforced and said such investments could eventually lead to massive cost savings as the nation’s health disparities are reduced.

“An equitable clinical research enterprise would include trials and studies that match the demographics of the disease burden under study,” the report said. “However, we remain far from achieving this goal.”

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The report cited many studies that show a lack of diversity persists in clinical trials — even for diseases that disproportionately impact non-white populations. One Food and Drug Administration analysis of clinical trials conducted between 2015 and 2018 showed that 78% of participants were non-Hispanic white people. More than 97% of participants in a Phase 2 trial of the Alzheimer’s drug crenezumab were white and just 2.8% were Hispanic even though Hispanic people are 1.2 times more likely to develop Alzheimer’s, the report said.

This lack of diversity has stubbornly persisted despite decades of attention to the issue, dozens of reports, and the creation of new offices in federal agencies to encourage broader participation in trials. A 2015 Government Accountability Office report found little improvement in trial diversity had occurred since 2004. To this day, the new report said, “research participants remain mostly white and male.”

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The report’s authors noted that diversity targets for clinical trials are seldom enforced, and they urged better tracking of the diversity of trial participants, withholding of funding for trials that do not meet goals, and offering tax credits or other financial incentives for those who do increase representation.

To illustrate why diversity in clinical trials is critical, the report’s authors cited the blood clot inhibitor warfarin as a cautionary tale. While the drug has been approved for use since 1951, it was not until 2013 that scientists realized genetic ancestry impacted how the drug should be dosed. Many people with Asian ancestry require lower doses and suffered excess bleeding when the drug was used at dosages set after trials conducted on mostly white men, the report said.

The authors cited other serious issues caused by the lack of diversity, including the inability to generalize research to the larger U.S. population; difficulty recruiting enough participants for many studies, which is the leading cause of clinical trial failure; and a lack of trust in the clinical research and medical establishments by those who have been historically excluded from clinical trials.

An economic analysis commissioned as part of the report showed that billions could be saved by reducing the harms caused by diabetes and heart disease if just 1% of health disparities were reduced though more diverse clinical trials. “As the U.S. becomes more diverse every day, failing to reach these growing communities will only prove more harmful and costly over time,” the report’s chair, Kirsten Bibbins-Domingo, said in a statement.

The cost of these disparities goes beyond dollars.”While it’s easy to calculate the economic costs, it’s impossible to fully calculate the emotional trauma associated with inequities in health care,” committee member Jason Resendez, president and CEO of the National Alliance for Caregiving, told STAT.

Bibbins-Domingo, a professor at the University of California, San Francisco, and the incoming editor of the Journal of the American Medical Association, said the issue of representation in clinical trials became urgent for her in 2017, when she chaired the U.S. Preventive Services Task Force and found few studies to help her assess how guidelines should differ for racial and ethnic populations with higher medical risk factors or medical needs. It was also the year her father died of prostate cancer. While the cancer has an incidence 75% higher in Black men, Bibbins-Domingo found that Black men made up fewer than 5% of enrollees in prostate cancer clinical trials and fewer than 2.5% of those in late-stage clinical trials, a disparity she called “acutely distressing.”

The report, commissioned by Congress and sponsored by the National Institutes of Health, found that some progress has been made. For example, women now represent half of subjects in clinical trials. But that progress has largely benefited white women, the authors said. They called the representation of racial and ethnic minority groups — both men and women — in clinical trials “largely stagnant, with little changes in diversity over time.”

Other understudied groups, the authors said, include older adults, those who are pregnant or lactating, LGBTQIA+ individuals, and people with disabilities.

The authors pushed back against the assumption many researchers hold that people from historically underrepresented groups do not want to participate in clinical trials due to mistrust. They said evidence shows that people from these groups are “no less likely, and in some cases, more likely, to participate in research if asked.”

Instead, they pointed to other barriers, including rules that limit compensation to trial enrollees and industry-funded research that forces participants to pay out-of-pocket expenses and puts time pressure on researchers to recruit and gather data quickly.

The authors also noted that an excuse for not recruiting diverse populations commonly used by researchers — that studying subgroups of populations would lead to studies that were “underpowered,” or too small for meaningful statistical analysis — needed to be set aside as well because the lack of inclusion in clinical trials was exacerbating health disparities. Even small sample sizes could lead to new and important testable hypotheses, the report said.

The committee said it found mountains of evidence that research trials lacked diversity, but very little scholarly work on how to combat the problem. To deal with this dearth of information, the panel worked with 20 researchers who had successfully conducted clinical trials that met the criteria for diverse enrollment to come up with suggestions:

  • Start with the intention of achieving diversity, including partnering with community agencies, designing studies that recruit diverse groups, and anticipating and removing barriers to participation such as by simplifying complex consent language or offering participants evening or weekend appointments so they don’t need to miss work.
  • Establish trust, something that takes time and may require planning studies at very early stages with community groups researchers hope to partner with, and provide them funding. (The report cited the success of the Milwaukee office of the Wisconsin Alzheimer’s Institute, which has worked closely with Black community leaders since 2008 and seen a 400% increase in participation in research projects.)
  • Work to identify stakeholders that may not traditionally have played roles in clinical studies, such as caregivers, religious leaders, or community advocates.
  • Be prepared that colleagues and funding agencies may not understand or appreciate the challenges and costs of working to be inclusive in clinical trial research.
  • Have a diverse research team.
  • Increase budgets to recruit and retain diverse communities, and support partnerships with community organizations.
Source: STAT