Modifying Eligibility Criteria to Promote Female Participant Inclusion in Research

Clinical Researcher—August 2026 (Volume 40, Issue 4)

PEER REVIEWED/LETTER TO THE EDITOR

Hannah J. Schmit, BA[1]; Eric Garshick, MD[2,3]; Vincent S. Fan, MD[4,5]; Farrah Kheradmand, MD[6,7]; Demerise Johnston[2]; Christine H. Wendt, MD[1,8]

 

Dear Editor,

Ensuring robust female representation in both clinical and observational studies is vital for producing generalizable findings and improving women’s health.{1} Despite significant efforts to include women and minorities in clinical research,{2,3} persistent gaps in participation still exist.{4,5}

A key challenge lies in balancing participation with safety measures designed to protect female participants, particularly those of childbearing potential, from the risks associated with certain inventions and/or exposures.{4} While these protective practices are necessary, they can inadvertently create unnecessary or overly restrictive barriers to clinical trial enrollment. In addition, some of these mandated safety protocols may be irrelevant to certain participants, hindering their access for participation.{2}

While recruiting Veterans from the Department of Veterans Affairs (VA) Cooperative Study #595, “Service and Health Among Deployed Veterans,” for supplemental testing including a high-resolution chest CT scan, we encountered barriers in enrolling female Veterans of childbearing age. Specifically, exclusion criteria were implemented to mitigate the risks associated with radiation exposure in women of childbearing age that proved to be too restrictive.

When the study was initially approved, we adopted informed consent language based on the template provided by our institutional review board. These criteria defined childbearing potential as individuals who are pre-menopausal and have not undergone a hysterectomy or surgical sterilization. To be eligible, female Veterans of childbearing potential were required to utilize birth control for the previous three months, have a negative pregnancy test, and maintain the use of birth control for the duration of the study (one study visit).

This birth control requirement based on the templated language proved to be a significant barrier. It excluded participants not at increased risk of pregnancy, where contraception was irrelevant. Examples included: same-sex relationships, monogamous relationships with infertile male partners (e.g., vasectomy), and documented infertility due to prior therapies or conditions.

Of 40 women screened between July 2022 and September 2024, 10 were ineligible based on lack of contraceptive use and childbearing potential. By eliminating the birth control requirement, eight out of the 10 participants who would have otherwise been excluded based on childbearing potential became eligible and were able to participate in the study. This increased the overall eligibility for female Veterans from 75% (30/40) to 95% (38/40) (P=.008, McNemar exact test).

Our study inclusion criteria still included the requirement for a negative pregnancy test to ensure study safety and a negative response to the question “are you pregnant or think you may be pregnant.” The protocol change addressing the relevance of contraceptive use increased the overall eligibility of female participants but did not increase risk.

This case highlights how, despite the increased effort to include women in clinical research trials, unanticipated barriers still exist. This has implications in studies where exposure to radiation, certain procedures, and/or drug administration can limit inclusion. We recommend that exclusion criteria that could disproportionately impact participation for women should be regularly reviewed and tailored to fit individual needs to create more inclusive and representative studies.

Funding

Department of Veterans Affairs (VA) Office of Research & Development (ORD) Cooperative Studies Program Study #595, and VA BLR&D I01 BX004619, I01 BX004633, I01 BX004609-01A1 from PACT Act Toxic Exposure Funds through the VA ORD Military Exposures Research Program. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.

References

1. Nijjar SK, D’Amico MI, Wimalaweera NA, Cooper NAM, Zamora J, Khan KS. 2017. Participation in clinical trials improves outcomes in women’s health: a systematic review and meta-analysis. BJOG124:863–71. https://doi.org/10.1111/1471-0528.14528
2. U.S. Department of Health and Human Services, issuing body, et al. 2020. Enhancing the Diversity of Clinical Trial Populations: Eligibility Criteria, Enrollment Practices, and Trial Designs. Center for Drug Evaluation and Research. https://www.fda.gov/media/127712/download
3. National Institutes of Health. 1993. NIH Revitalization Act of 1993: Subtitle B—Clinical research equity regarding women and minorities. https://orwh.od.nih.gov/sites/orwh/files/docs/NIH-Revitalization-Act-1993.pdf
4. Institute of Medicine (U.S.) Committee on Ethical and Legal Issues Relating to the Inclusion of Women in Clinical Studies, Mastroianni AC, Faden R, Federman D (Eds.). 1994. NIH Revitalization Act of 1993 Public Law 103-43. In Women and health research: Ethical and legal issues of including women in clinical studies: Volume I. National Academies Press. https://doi.org/10.17226/2304
5. Daitch V, Turjeman A, Poran I, Tau N, Ayalon-Dangur I, Nashashibi J, Yahav D, Paul M, Leibovici L. 2022. Underrepresentation of women in randomized controlled trials: a systematic review and meta-analysis. Trials23(1):1038. https://doi.org/10.1186/s13063-022-07004-2

Author Affiliations

[1] Minneapolis VA Health Care System, Minneapolis, Minn.

[2] VA Boston Healthcare System, Boston, Mass.

[3] Harvard Medical School, Boston, Mass.

[4] VA Puget Sound Health Care System, Seattle, Wash.

[5] University of Washington, Seattle, Wash.

[6] Michael E. DeBakey VA Medical Center, Houston, Texas

[7] Baylor College of Medicine, Houston, Texas

[8] University of Minnesota, Minneapolis, Minn.