Diversity Mandate for Clinical Trials Aids Review Boards’ Role

New clinical trial diversity requirements should help panels charged with ethics reviews of human studies, even if they don’t have to review the plans directly, research specialists said.

Drug and device companies and other clinical trial sponsors must submit a diversity action plan in the studies the Food and Drug Administration uses to decide whether to approve a medical product. The new requirement came about in the DEPICT Act (Public Law 117-164), which Congress enacted late in 2022.

DEPICT aims to address a longstanding challenge of underrepresentation in clinical trials. Racial and ethnic minorities make up almost 39% of the US population, but their inclusion rate in research ranges from 2% to 16%, according to Syneos Health.

The law largely codifies FDA draft guidance issued last year. That guidance and the DEPICT Act combined offer the “opportunity to move the needle more so than before,” Rachael Fones, strategic adviser for diversity in clinical trials for the clinical research organization giant IQVIA, said.

Ethics Panel Review

All research must pass a review by an ethics panel known as an institutional review board (IRB) if the study involves human subjects, and is either FDA-regulated or federally funded.

The human research protections regulations known as the Common Rule (45 C.F.R. 46) aim to protect study volunteers from undue harm in part by requiring their consent and making sure they understand the risks and benefits of enrolling. IRBs are empowered to reject research plans or ask for additional information before a researcher can enroll anyone.

The Common Rule also calls for addressing “equitable selection of subjects,” and some interpret “equitable selection” as including diversity in the study population.

But DEPICT doesn’t mention IRBs, so their responsibilities under the new law still aren’t clear.

“IRBs are expected to understand the recruitment process and approve recruitment materials, and these plans will clearly be linked to those efforts,” David Borasky, vice president of IRB compliance at WCG IRB, one the nation’s largest commercial IRBs, said.

But how IRBs will assess the adequacy of these plans or provide diversity training remains unanswered, he said.

“For example, if the FDA approves a sponsor’s IND, should the IRB consider this a signal that the FDA has determined that the plan is adequate?” Borasky asked, referring to investigational new drug applications.

The FDA needs to issue guidance clarifying the boards’ role quickly, Borasky said.

The FDA said in a statement that it’s reviewing and evaluating how to implement the provisions of the new law while engaging with stakeholders on enrolling diverse clinical populations.

Several research attorneys said they don’t expect IRBs to review and approve the diversity plans themselves.

The law imposes new requirements for trial sponsors, whereas IRBs tend to work with documents submitted by investigators.

“IRBs and sponsors typically don’t have direct interaction,” Elisa A. Hurley, executive director of Public Responsibility in Medicine & Research, said. But IRBs “absolutely” have a role in ensuring clinical trials are more diverse.

Immediate Changes Unlikely

Diversity plans can offer another set of information IRBs can use, but they’re unlikely to prompt immediate regulatory changes, Heather H. Pierce, senior director for science policy and regulatory counsel for the Association of American Medical Colleges, said.

IRBs are not “typically having discussions that would allow them to assess from one trial to another whether any one specific diversity action plan is adequate,” Pierce said. But the plans “may well begin to give additional insight into the types of questions that [IRBs] should be asking, if there’s something they don’t see in future plans or future approaches.”

IRBs should require sponsors to integrate these diversity plans into the overall research plan, as part of a larger effort to integrate equity into the standard procedures for conducting clinical research, said Yasmeen Long, a director at FasterCures who heads up its health equity programs.

The research protocol, informed consent, and recruitment documents all require IRB approval, Long said. “When you come to the IRB with your research plan, that is exactly when these requirements should be embedded.”

Mark Barnes, an attorney with Ropes & Gray LLP whose specialties include the ethics and regulation of clinical trials, said he expects IRBs would be influenced by guidance that FDA would produce on the issue of enhancing opportunities for more equitable enrollment in clinical trials.

“IRBs are required under the [Common Rule] to evaluate certain aspects of proposed studies, in light also of the ethical precepts articulated in the Belmont Report. One of those is, of course, equity,” Barnes said. The 1970s Belmont Report laid the ethical foundation for the Common Rule, which is administered by the Health and Human Research Office for Human Research Protections.

Barnes has played an integral role on an external advisory panel for OHRP since the late 1990s. Once FDA has issued its guidance on these issues, he said OHRP would likely produce its own complementary or corresponding guidance, which “would then be firmly established as expectations for investigators, IRBs, and institutions in designing and conducting interventional trials.”

IRB reviews typically focus on weighing the risks and benefits of the research as well as scrutinizing the informed consent, which have specific regulatory criteria, such as a description of which procedures are involved and a statement that participation is voluntary, Hurley said.

Equitable selection of subjects has tended to be secondary, she added.

“There’s probably been a lot of just relying on the research team,” and assuming they know who their study population should be,” Hurley said. " it just hasn’t been as much on the radar.” But the larger focus on diversity has empowered IRBs to ask in which populations is this disease most prevalent, and how will researchers reach those people?

Pay for Participation?

There’s already work in this space. The Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard University created a tool kit on diversity, equity, and inclusion. The HHS Secretary Advisory Committee on Human Research Protections released recommendations, calling on IRBs to “suggest ways to minimize the burdens of research to enable broader, more equitable participation.”

That ongoing discussion is already shifting perspective on whether it’s okay to pay study volunteers, Hurley said. Historically, IRBs have shied away from payments out of concern of coercion or undue influence.

But there’s growing recognition that fair and reasonable compensation might be key to recruiting diverse populations and people from underrepresented communities. “The tide might really be changing,” she said. “And in fact, not paying people could be exploitative.”