Filling the Regulatory Gap: Potential Role of Institutional Review Boards in Promoting Consideration of Sex as a Biological Variable

Abstract

Consideration of sex differences in biomedical research is crucial to ensure the safety and effectiveness of drugs and devices for both sexes and to improve the rigor and reproducibility of scientific discoveries. Historically, women were underrepresented in clinical research and sex differences typically were not considered. The U.S. Food and Drug Administration (FDA) and the National Institutes of Health (NIH) have played a role in improving the representation of women in clinical trials and in encouraging the consideration of sex differences. As it is not appropriate for all studies to be reviewed by the FDA nor do all studies have NIH funding, this results in a regulatory gap. We propose that local institutional review boards (IRBs) and institutional animal care and use committees (IACUCs) provide greater oversight by encouraging researchers to consider sex as a biological variable (SABV) during protocol review. In this perspective article, we review how FDA and NIH policies have fostered change and highlight how IRBs and IACUCs could encourage investigators to consider SABV.

Biomedical Researchers' Perceptions of the NIH's Sex as a Biological Variable Policy for Animal Research: Results from a U.S. National Survey

“…While some scholars have called for the SABV policy to extend beyond NIH-funded research to encourage more scientists to design and analyze their studies to capture potential sex differences, 13 this survey reveals there is no significant difference in the likelihood of analyzing results by sex between researchers who have and who have not recently received NIH funding. Despite likely being subject to the SABV policy, almost half of surveyed recent recipients of NIH funding are not conducting sex-based analysis of their findings for all of their studies.…”

Evaluating the National Institutes of Health's Sex as a Biological Variable Policy: Conflicting Accounts from the Front Lines of Animal Research

“…Consequently, some commentators recommend that the SABV policy be more comprehensively incorporated into the research enterprise so that all animal researchers, not just NIH-funded investigators, are encouraged to consider how sex might be important to their research questions. 23 The limitations of this study should be considered when interpreting these findings, including that we did not collect standardized information about when and if interviewees had received NIH funding or served as NIH grant reviewers. Additionally, semi-structured interviewing does not allow for quantitative reporting of findings or subgroup analyses in terms of demographic differences among interviewees.…”

“…Consequently, some commentators recommend that the SABV policy be more comprehensively incorporated into the research enterprise so that all animal researchers, not just NIH-funded investigators, are encouraged to consider how sex might be important to their research questions. 23 …”

Ensuring that biomedical AI benefits diverse populations

“…Where regulatory agencies such as the FDA, International Medical Device Regulators Forum, or European Medicines Agency have no jurisdiction, Institutional Review Boards (IRB) may provide oversight to ensure that sex, gender, race, and ethnicity analyses are appropriately integrated into research with enhanced and rigorous reviews. An important part of US IRBs' remit is to ensure that study designs are sound [49]. If study participants are limited to the institution's geographic location, however, the limits of the study should be clearly stated.…”