What Difference Does Sex Make?

Drug development needs to study the effects of drugs and biological products on women, as well as men.

By Christopher R. McCurdy, Ph.D., FAAPS, President 

In November 2017, the National Institutes of Health (NIH) amended its Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research. The amendment required that “conducting applicable NIH-defined Phase III clinical trials ensure results of valid analyses by sex/gender, race, and/or ethnicity are submitted to Clinicaltrials.gov.”¹

For some background, the NIH Revitalization Act of 1993 directed NIH to establish guidelines for including women and minorities in clinical research, and the 21st Century Cures Act requires entities conducting applicable clinical trials to submit results of valid analyses by sex/gender, race, and ethnicity in Clinicaltrials.gov. Future NIH grants would rely on compliance with this reporting requirement.

Also in 1993, the Food and Drug Administration (FDA) published the Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs. The guideline addressed concerns that the drug development process did not provide adequate information about the effects of drugs or biological products in women. It lifted the restriction on the participation of women with childbearing potential from entering phase 1 and early phase 2 trials and instructed sponsors to collect gender -related data and analyze it for gender -related effects. (Women with childbearing potential were excluded from clinical trials after the thalidomide tragedy.)

In a September 2015 NIH Outreach Toolkit, the agency reported that roughly half of NIH-funded clinical trial participants are women. However, gaps in the research existed across gender, race, and ethnicity, especially at the intersection of these three characteristics. The toolkit provides successful practices for engaging people in clinical studies, guidelines on conducting outreach, and a series of case studies.²

In October 2017, NIH held a workshop on Sex as a Biological Variable that addressed sex differences in brain function and behavior, sex effects/interactions with external influences, sex differences in animal models, and sex differences in gene expression. (A video of the workshop sessions is available on the NIH website.³) Moreover, NIH is requiring the exploration of sex differences in animal research as a key aspect of scientific rigor in grant applications.

FDA has an Office of Women’s Health (OWH), established by congressional mandate to advocate for women’s participation in clinical trials and the analyses of data by sex. The OWH supports studies tracking women’s participation in clinical trials and works with other FDA centers and others to conduct training, workshops, outreach, and research to improve clinical trial design, recruitment, and analyses.⁴

Its website includes information on FDA guidance and regulations, tools and resources for researchers (including online CE courses and webinars), OWH-funded clinical trials research, conferences and workshops, and the OWH Sex and Gender Speaker Series for FDA Reviewers.

Over the years, AAPS has addressed sex differences in offerings at its annual events. The 2016 AAPS Annual Meeting and Exposition had a session on Toward Precision Therapies: Understanding Age and Sex Differences in CNS Diseases, and the 2015 annual meeting presented the roundtable Inclusion of Women in Clinical Trials and Drug Development. Posters have addressed sex differences in clinical research, adverse outcomes for new FDA-approved drugs, and in exposure for FDA-approved new molecular entities. AAPS encourages more programming centered around sex differences in basic and clinical research. Please send in your programming ideas to VoelkelM@aaps.org, or initiate and join discussions in our community forum.  

References

1. Amendment: NIH Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research webpage. National Institutes of Health website. Accessed January 19, 2018.
2. An NIH Outreach Toolkit: How to Engage, Recruit, and Retain Women in Clinical Research webpage. National Institutes of Health website. Accessed January 19, 2018.
3. Sex as a Biological Variable Workshop webpage. National Institutes of Health website. Accessed January 19, 2018.
4. FDA Research, Policy, and Workshops on Women in Clinical Trials. FDA website. Accessed January 19, 2018.