Collecting data from both male and female volunteers is critical for appropriate evaluation of clinical trial outcomes. FDA’s latest guidance document outlines what the FDA expects when it comes to enrolling male and female participants, analyzing results by sex, and sharing this information in clinical study reports. Although this issue has been discussed extensively for clinical trials with drugs and biologics, this is the first guidance about similar issues in medical device trials.
The FDA’s guidance lists methods to improve the enrollment, analysis, and reporting of sex-specific data in clinical studies supporting medical device approvals. Clinical trials should describe how medical devices perform in both women and men by requiring thorough sex-based data analysis and reporting. The guidance underscores the need to consider sex differences due to biological, anatomical, and physiological factors that may influence device performance. It provides several clinical examples where device outcomes varied significantly between men and women, including higher stroke rates in women using Ventricular Assist Devices, greater benefit from CRT-Ds observed in women versus men, and higher revision rates in women with metal-on-metal hip implants. These differences are attributed to sex-specific factors such as hormonal influences, body size, disease prevalence, and comorbidities, reinforcing the necessity to design and interpret studies with sex as a key variable.
Historically, women have been underrepresented in medical device clinical studies for several reasons: concerns about potential pregnancy risks, exclusion criteria that unintentionally disqualify women (e.g., upper age limits or body size thresholds), lack of awareness about disease differences, and logistical challenges like caregiving responsibilities. Investigators and sponsors may also avoid enrolling women due to perceived recruitment challenges. The guidance calls for addressing these issues by identifying barriers at every stage—from screening and consent to follow-up—and modifying study protocols accordingly. For instance, it suggests considering flexible follow-up scheduling, child care support during appointments, and targeted recruitment at women’s clinics.
To ensure balanced enrollment, the FDA recommends that sponsors prospectively set enrollment targets reflecting the sex-specific prevalence of the condition under study. Study designs should incorporate statistical plans that assess heterogeneity in outcomes by sex. This includes pre-specifying tests for treatment-by-sex interaction and adjusting for potential confounding variables like age or comorbidities. When designing diagnostic devices or assays, sex-specific cutoffs or reference intervals should be justified by evidence, and performance measures like sensitivity and specificity should be evaluated separately for each sex.
The guidance places a strong emphasis on how sex-specific data should be analyzed and reported. Sponsors are expected to include descriptive and inferential statistics by sex for all primary and key secondary endpoints, even if subgroup sizes are small. Clinically meaningful differences should be interpreted carefully and discussed with the FDA to determine if further data collection is necessary. Public-facing documents like product labeling, summaries of safety and effectiveness, and de novo summaries should transparently include sex-specific results. If clinically significant differences are observed, FDA may require updated labeling or additional confirmatory studies in one or both sexes. Overall, the guidance promotes equitable and evidence-based decision-making by ensuring sex-specific factors are fully integrated into medical device evaluation.
The main goal is to make sure studies include enough people from each sex and that their results are reviewed separately to help improve the quality of data on how devices work for both men and women. This guidance applies to all medical device clinical trials. It supplements existing device-specific guidance and should be considered across the device lifecycle.
