Sex Matters: Research for All Act Seeks to Facilitate the Research, Development, and Approval of Drugs With an Eye Towards Male and Female Differences

By Kurt R. Karst –      

Interest in and efforts to address shortfalls in the inclusion of women in clinical trials and clinical research, and differences in the sexes in drug development are not new.  There’s the National Institutes of Health (“NIH”) Revitalization Act of 1993, which directed the NIH to establish guidelines for inclusion of women and minorities in clinical research, as well as FDA’s 1993 “Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs.”  Less than a decade later, the U.S. Government Accountability Office (“GAO”) issued two reports – in May 2000 (“NIH Has Increased Its Efforts to Include Women in Research”) and August 2001 (“Women Sufficiently Represented in New Drug Testing, but FDA Oversight Needs Improvement”) – addressing the issues.  But a 60 Minutes report last February highlighting how the drug AMBIEN (zolpidem) metabolizes differently in males and females reignited interest in the topic. 

Shortly after the 60 Minutes piece aired, the NIH announced that it will change its policies to ensure that female animals and cells are included in research and sex differences analyzed, and members of Congress penned letters to FDA and the GAO (here and here) seeking further information.  These moves were  promptly applauded (here and here) by the Society for Women’s Health Research, which has also held a congressional briefing on the need for sex- and gender-based research.  Other organizations have also recently pressed for sex-specific clinical research (see, e.g., here). 

Then the U.S. Senate in its Fiscal Year 2015 FDA Appropriations Bill & Report (see our previous post here) directed FDA to look closer at gender differences in clinical research:

Inclusion in Clinical Trials– Research has shown that gender differences, as well as differences based on age, race, or other factors, may contribute to differences in the safety and efficacy of drugs, biologics, and devices.  The Committee directs FDA to encourages diverse participation, including women, racial and ethnic minorities, and the elderly, to help assure that clinical trials are representative of those individuals who ultimately will use these medical products, and that the products will be safe and effective for people in these demographic subgroups.  The Committee urges the FDA to issue the Action Plan required by section 907 of the Food and Drug Administration Safety and Innovation Act [(“FDASIA”)] and provide a timeline for implementation of the actions FDA will take, in cooperation with industry stakeholders, to ensure that women, minorities, and others are appropriately represented in clinical research, that meaningful subgroup analyses of clinical trials are conducted, and that subgroup specific clinical trial results are made publically available in an accessible and timely manner.

By way of background, FDASIA 907 requires FDA to publish an action plan on the Agency’s website with recommendations on improving the completeness and quality of data analyses on demographic subgroups, including such data in labeling, and making such data available to patients and providers.  FDASIA 907 also required FDA to issue a report describing the participation of demographic subgroups (sex, age, race, and ethnicity) in clinical studies submitted to FDA in marketing applications.  FDA issued that report in August 2013 (available here).

Now, two members of Congress are ratcheting up debate on the “sex matters” issue.  Earlier this week, Representatives Jim Cooper (D-TN) and Cynthia Lummis (R-WY) announced the introduction of H.R. 4879, the “Research for All Act of 2014.”  The bill would require FDA to “review and develop policies, as appropriate, to ensure that the design and size of clinical trials for products granted expedited approval pursuant to [FDC Act § 506] are sufficient to determine the safety and effectiveness of such products for men and women using subgroup analysis.”  Indeed, the bill would amend FDC Act § 506 (“Fast Track Products”) to add a new subsection, titled “Expedited Review of Drugs and Biological Products To Provide Safer or More Effective Treatment for Males or Females,” under which a drug sponsor could request that FDA designate a product intended to avoid serious adverse events or to treat a serious or life-threatening disease or condition “as an expedited product to provide safer or more effective treatment for males or females.”  Such a designation would provide early and frequent communication with FDA, as well as so-called rolling review of marketing applications.

The Research for All Act of 2014, which was introduced on the same day that some lawmakers sent a letter to NIH requesting that it make demographic data public for all clinical trials, would also amend the PHS Act to require that basis research involving cells, tissues or animals to include both male and female cells, tissues, or animals; update guidelines for clinical and basic research to reflect the growing understanding that sex differences matter, and to ensure better enforcement of those guidelines by NIH, among other things; and require the GAO to update the May 2000 and August 2001 reports mentioned above.

The Research for All Act of 2014 is one of a growing number of FDA and drug-related bills pending in Congress (see our FDA Legislation Tracker).  Although it is unlikely that most of them will be enacted by the time the 113th Congress ends, we may see some of them crop up again as folks seek to lay the groundwork for the next iteration of UFA (User Fee Act) reauthorization.