Multiple 2021 studies demonstrate the long-standing problem of certain groups remaining underrepresented in clinical trials.1-3 IRBs are demanding much more of researchers in this regard. “It is a topic on the minds of PIs [principal investigators] and IRBs lately,” says Lucas Sikorski, BA, CIP, senior IRB analyst at Northwestern University. 

Current regulations that govern IRB review of human subjects research require equitable selection.4 “But the regulations don’t have any more specific way of attesting this or determining this. It is kind of vague about how it should be assessed,” Sikorski explains.

Researchers typically recruited the people they saw in the course of their clinical practice. “Historically, we have accepted that PIs recruit from their clinical population, and this was considered an acceptable population source,” Sikorski notes.

Northwestern’s IRB has been encouraging investigators to go beyond this, and consider if they are meeting the intent of the regulatory criteria for equitable selection. “There’s definitely a push to be cognizant of the potential participant pool that may be eligible for the study,” Sikorski reports.

IRBs want to see investigators recruit outside their clinics if the people they see regularly do not include underrepresented groups. This might be the case with community-centered studies or investigations of a specific population that is not necessarily treated in a clinic (e.g., a specific LGBTQ+ population). Overall, IRBs want to see researchers conduct more community outreach, with an eye toward including diverse participants.

“That takes more resources, but we are seeing more expectations for that kind of outreach,” Sikorski says. “Having a diverse data pool will lead to more accurate results. It makes for better science.”

Previously, the status quo was for protocols to exclude non-English speakers, and IRBs usually accepted this. “But now we don’t accept that as a de facto exclusion criterion out of convenience,” Sikorski says.

If a protocol excludes non-English speakers, the IRB will want to know why. “We might still accept a lack of resources as a justification. It would depend on the study, the target population, and the size of the enrollment goal,” Sikorski explains. “It may be harder to justify if it’s a wide-ranging and large target population.”

To meet IRB approval, Sikorski says researchers should include people fluent in non-English languages on the study team, or otherwise be able to access non-English speakers. Also, he says to create plans for translating all subject-facing documents and to make non-English study staff available as part of recruitment, consent, and study visits.

Researchers might initially use the short consent form process for a non-English speaking participant. However, after encountering several such cases, the team would translate the consent form.

“Informed consent is all about communication and understanding,” Sikorski observes. “If you don’t have the tools or the resources to make sure that communication is transparent and understandable, it’s a problem.”

Existing guidance has focused mainly on detecting and preventing exploitation and coercion of research participants.5 “But that focus has evolved and expanded. The growing emphasis on including those underrepresented in clinical research is shared by IRBs,” says Madelon V. Baranoski, PhD, chair of the IRB at Yale Medical School.

Increasingly, IRBs view the equitable selection of participants as a responsibility of investigators. “The expanding concerns reflect the evolving appreciation of the ethical principle of justice,” Baranoski says. All in a community have the right to know about the research conducted and to be able to participate. Reliable and generalizable research results require full representation. “The obligation of the research institution, therefore, is to remove barriers to participation,” Baranoski says.

For IRBs, this means identifying specific barriers in protocols and exploring ways to mitigate them. “Language can be a barrier to including people from different backgrounds,” Baranoski says.

IRBs may require materials be translated into a language that is common to a significant segment of the community. The IRB also may require making translation services available during the study visits. “The cost of travel and parking may be prohibitive to persons with low income,” Baranoski notes.

If so, reimbursement for cost or providing a free parking area would make research more accessible. Likewise, providing evening and weekend times for study visits can reduce the burden of participants who would have to lose a workday to enroll.

Traditionally, researchers relied on notices or brochures in physicians’ offices to alert people about clinical trials.

“To reach a broader population, however, recruitment, education, and a two-way discussion of the research is best accomplished by going into the community to invite citizens to engage with the researchers,” Baranoski offers.

The issue is not just about recruitment. “Equitable, diverse, inclusive, and just participation in research begins long before recruitment of subjects,” notes Linda Coleman, JD, CIP, CHC, CHRC, CCEP-I, director of the Yale University Human Research Protection Programs. Groups underrepresented in research must be involved in research design, methods, the consenting process, and in formulating the research questions. “Science, medical care, investigators, and communities will all benefit,” Coleman says.

To address obstacles that interfere with equitable recruitment of participants, the Yale IRB requires investigators to gather input from the Cultural Ambassador Program. This group “educates investigators about the community and educates the community about research,” Coleman explains.

The IRB and study investigators have benefitted from the ambassadors’ consultation in several ways. Previously, the prevailing attitude was that underrepresentation in research stemmed from community resistance. The ambassadors gave feedback, suggesting the onus is on researchers to build trust in the community. Today, investigators present protocols at churches, mosques, synagogues, high schools, nursing homes, and community groups.

Additionally, investigators have made changes to reduce the effect of missing a workday to participate in studies. Researchers offer evening and weekend hours; telehealth visits; and reimbursement for parking, transportation, and child care.

Despite these positive changes, obstacles to accessibility remain. “There are economic, practical, and regulatory limits on what IRBs can require,” Coleman laments.

Equitable selection is not the responsibility of investigators alone. “Promoting equitable participation must not be at the cost of impeding research,” Coleman stresses. “Within an ethical framework beyond regulations, however, IRBs are evolving to address and accelerate equitable inclusion in research.”

REFERENCES

  1. Flores LE, Frontera WR, Andrasik  MP, et al. Assessment of the  inclusion of racial/ethnic minority, female, and older individuals in vaccine clinical trials. JAMA Netw Open 2021;4:e2037640
  2. Nguyen HT, Zheng A, Gugel A, Kistin CJ. Asians and Asian subgroups are underrepresented in medical research studies published in high-impact generalist journals. J Immigr Minor Health 2021;23:646-649. 
  3. Tharakan S, Zhong X, Galsky MD. The impact of the globalization of cancer clinical trials on the enrollment of black patients. Cancer 2021;127:2294-2301.
  4. 45 CFR Code of Federal Regulations 46.111. Criteria for IRB approval of research.
  5. HHS.gov. Approval of research with conditions: OHRP guidance. Nov. 10, 2010.