What the IRB Is Looking for When Reviewing Reproductive Health Research Studies

Assisted reproductive technology (ART) can be leveraged to address reproductive justice issues, offering options for individuals who wish to have children. However, as research moves toward new ARTs , both the FDA mandate and ethics require us to ensure equitable access. Trends around access to currently available ARTs, such as in vitro fertilization (IVF) can serve as a proxy for identifying prospective gaps in access and representation that may present in the future in both the research and clinical setting. Importantly, ARTs such as IVF can also be used as a reference for identifying what an Institutional Review Board (IRB) looks for when assessing a new protocol submission, with an eye to justice.

Current research points to significant disparities in ART utilization and outcomes. There are several factors contributing to these disparities, from structural racism to lack of access to culturally responsive care. Financial barriers, such as lack of insurance coverage, leave underinsured individuals at higher risk of being underserved by ART.¹ For example, one study found that Asian/Pacific Islanders reported the highest number of ART procedures per million women between the ages of 15 and 44 (5883.0), followed by white non-Hispanic women (2888.4). Conversely, Black non-Hispanic, Hispanic, and American Indian/Alaska Native women reported dramatically lower rates of ART procedure utilization (1434.0, 996.7, 806.8, respectively). However, insurance coverage was not the sole cause of the inequity. This research indicates that while insurance coverage did increase rates of ART procedure utilization, the disparities observed between racial/ethnic groups was maintained.¹ Furthermore, Black non-Hispanic identifying women are also twice as likely to report experiencing infertility when compared to white identifying individuals.²

Regardless of the source of these disparities, the result is that Black, Indigenous, and other people of color (BIPOC), along with underinsured individuals, are less likely to receive infertility services despite exhibiting a greater need for such services.

With these disparities in mind, the question for the research community is how Sponsors, investigators, and regulatory bodies, like the IRB, can collaborate to improve representation in ART research.³ For the IRB this means reviewing eligibility criteria, recruitment methods, along with other barriers and facilitators, and how these factors combine to improve representation and clinical benefit.

Eligibility Criteria

Underrepresentation in the clinical setting contributes to, and is often led by, an underrepresentation in the research setting. If a study is not representative of the population it is intended to serve, then it is inherently inequitable, and may lack generalizability. When reviewing ART research, the IRB is looking for a study with clinically and ethically sound eligibility criteria. For example, if the issue under investigation scientifically impacts BIPOC and white individuals alike, then eligibility criteria should aim at generating a representative participant sample, with the goal of improving the generalizability of research findings.

Recruitment and Outreach

Where eligibility criteria create participant selection parameters, outreach and recruitment help support equitable selection. The Food and Drug Administration (FDA) views any direct study advertising as the start to the informed consent process. The IRB is tasked with reviewing such materials, ensuring that the materials meet the criteria for approval. Study outreach materials must avoid any claims that suggest an investigational drug, device or procedure is safe, while appropriately framing the product as “experimental.” Additionally, participant facing materials should not make promises of free medical treatment, or otherwise emphasize participant payment or compensation.⁴ If materials are designed to target a specific demographic, there should be adequate justification for this approach. Assuming targeted recruitment aligns with eligibility criteria, it is important to ensure that recruitment methods and materials are culturally and linguistically responsive.⁵ This may include incorporating identifiable imagery and other content, but may also involve taking a community-based participatory approach to research design and implementation and drawing on community leaders for guidance.⁶ While community-inclusive approaches are not a regulatory requirement, the IRB looks favorably on such methods when research aims to seek to include or even target underrepresented populations.

Focus on Participants Who Are Patients

The IRB is also tasked with considering the balance of research risks and benefits. An ART research study has the potential to provide benefit to participants, but it is not without risks. One way to reduce risk is to design the research around what patients are already undergoing as part of their routine medical care . For example, if an individual was proceeding with a specific ART treatment outside of the research context and could potentially benefit from enrolling in a study investigating a new variation of that ART, the baseline risks associated with procedures are arguably the same whether or not they participate in the study. This essentially lowers the research specific risks, resulting in a more favorable risk-benefit ratio.

However, as noted above, the average population currently receiving ART treatment does not meet the criteria for “equitable selection.” Depending on the population served by the clinic, limiting participation to those already undergoing related treatment is likely to exclude a huge segment of the affected population. As a result, this selection approach could have material impact on the results, limiting generalizability and potential benefit to society. This could be an appropriate starting place for early clinical trials operating with limited data from human subjects but should not be a long-term approach to eligibility and recruitment.

The inequality in participant selection could be offset by reducing the financial burden associated with research participation and access to ART services through participant compensation and payment for travel and related expenses. Reducing the economic burden may make research-based care more accessible, over standard clinical care. However, this may create a scenario where those unable to afford care outside of the research setting resort to seeking experimental care with more unknowns and potential risks. While participant compensation is generally acceptable, it is not considered a benefit and should be reasonable in the context of the research. In reviewing participant compensation, the IRB considers if the compensation is adequate in terms of offsetting participant time and effort, but not so much that the incentive presents an undue influence.⁷

Conclusion

Equitable healthcare starts in the research setting. Through thoughtful protocol design and utilization of culturally and linguistically responsive outreach materials, sponsors, investigators, and regulatory authorities can work together to generate representative and generalizable data for ART research and start to address reproductive justice issues.

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References

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548290/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349227/
3. https://www.fda.gov/media/127712/download
4. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recruiting-study-subjects
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144271/
6. Marrone, N., Nieman, C., & Coco, L. (2022). Community-based participatory research and human-centered design principles to advance hearing health equity. Ear and hearing, 43(Suppl 1), 33S.
7. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/payment-and-reimbursement-research-subjects