Posted 21 August 2014 | By Alexander Gaffney, RAC,

The US Food and Drug Administration (FDA) has released new recommendations on the inclusion of women and other minorities in clinical trials, citing the need to better represent populations which have historically not been adequately included in clinical research.

Background

When the Food and Drug Administration Safety and Innovation Act (FDASIA) was signed into law in 2012, among its many provisions was Section 907. The section required FDA to publish a report "addressing the extent to which clinical trial participation and the inclusion of safety and effectiveness data by demographic subgroups-including sex, age, race and ethnicity-is included in product applications submitted to FDA."

The thinking of regulators and legislators was that if a trial does not adequately represent patients who will ultimately use a medical product, that product may be more or less effective or safe in some of those populations.

For example, if a statin drug would be used equally by both men and women, a clinical trial that included mostly men might hide some adverse events experienced exclusively by women. Similarly, if a trial does not break out patient data by subgroup, it might not discover that a drug is less effective in patients of a particular race.

Draft Section 907 Report

When FDA released a draft of its Section 907 report to the public in August 2013, it said it found that most companies were already doing a good job at reporting differences experienced between men and women, but did less well when it came to analyzing or reporting factors such as race and ethnicity.

Regulators also found that "the extent to which demographic subset data were analyzed varied across medical product types," with devices falling far short of their drug and biological counterparts, which are required to collect much of the data by law.

FDA also cautioned about the usefulness of certain data they received. While some companies did submit data on age or sex differences, the size of the trial can limit the power and usefulness of that data, especially when subgroups are underrepresented to begin with.

The report caught the attention of some legislators, who have urged FDA to do more to require the inclusion of women and minorities in clinical trials.

New Developments

Now FDA has published two documents related to the Section 907 report: An action plan and a final guidance document, both of which are intended to introduce solutions to the report's noted deficiencies.

The action plan makes 27 recommendations, split up into three main "priority" groups: quality, participation and transparency.

FDA said it wants companies to "improve the completeness and quality" of the clinical data they collect and report, to identify barriers to subgroup enrollment, and to make subgroup demographic data "more available and transparent."

Among the extensive list of action items, FDA confirmed that it will be working to revise three guidance documents:

Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs

Collection of Race and Ethnicity Data in Clinical Trials

ICH E7 Studies in Support of Special Populations: Geriatrics

Regulators will also be revising medical product applications to "enhance" information on demographic subgroups, changing the way FDA collects age-related data to be more nuanced (i.e. not just "over 65 years of age"), researching drugs with potential problems, working to make sure exclusion criteria in trials are used appropriately, and posting demographic information for FDA-approved products.

The plan also notes that FDA's device review division, the Center for Devices and Radiological Health (CDRH), plans to study how health professionals view labeling to improve understanding and use. Information obtained from the study will inform future guidance documents on the subjects, FDA said.

Final Guidance

FDA's final guidance, Evaluation of Sex-Specific Data in Medical Device Clinical Studies, though focused on medical devices, is also an early look at how FDA plans to implement the 907 report in practice.

Device companies are advised in the guidance to consider potential sex differences, including prevalence of the condition, diagnosis and treatment pattern differences, clinically meaningful differences in outcomes, and the proportion of women included in past studies.

These recommendations will apply to ongoing, completed and post-market research, FDA said, and trials should be designed to accommodate outstanding questions and in particular sex-specific differences.

FDA Action Plan (FR)

Evaluation of Sex-Specific Data in Medical Device Clinical Studies (FR)

FDA Voice Blog Posting