Evaluation of Sex-Specific Data in Medical Device Clinical Studies
This guidance outlines FDA's expectations regarding sex-specific patient enrollment, data analysis, and reporting of study information in medical device clinical studies. It applies to devices requiring clinical information for marketing submissions (510(k), PMA, de novo, HDE) and post-approval studies. The guidance does not apply to devices intended for single-sex populations or certain IVD studies using de-identified specimens.
What You Need to Know? 👇
What are the key requirements for sex-specific enrollment in medical device clinical studies?
FDA recommends enrolling proportions of women and men that reflect the underlying disease distribution in the affected population. Studies should prospectively plan enrollment strategies and investigate barriers when women are underrepresented, unless the device is intended for single-sex use.
How should sponsors analyze sex differences in completed clinical studies?
All studies must report descriptive statistics by sex for primary effectiveness and safety endpoints. Sponsors should assess heterogeneity across sex groups using pre-specified statistical analysis plans and investigate treatment-by-sex interactions in comparative studies to detect clinically meaningful differences.
When is additional data collection required for sex-specific outcomes?
FDA may require additional pre-market or post-market data when clinically meaningful sex differences are observed, when there’s insufficient data to assess sex-related outcomes, or when statistical power is inadequate to detect important differences between sexes.
What statistical considerations apply to diagnostic devices regarding sex differences?
For diagnostic devices using cutoffs, sponsors must include data from both sexes during cutoff selection and validation stages. Separate cutoffs for men and women should only be used when previous evidence supports different thresholds based on clinical utility.
How should sex-specific information be reported in FDA submissions and labeling?
Submissions must report enrollment demographics by sex, baseline characteristics, and sex-specific outcomes. Labeling should describe clinically meaningful sex differences in safety or effectiveness, clearly distinguishing between pre-specified and post-hoc analyses with appropriate statistical context.
What strategies can improve women’s enrollment in medical device studies?
Effective strategies include targeting sites where women can be easily recruited, revising exclusion criteria that may inadvertently exclude women, providing flexible scheduling with childcare services, and investigating screening logs to identify enrollment barriers.
What You Need to Do 👇
Recommended Actions
- Develop strategy to enroll representative proportions of women and men
- Include pre-specified plans for sex-specific analyses in study protocols
- Report descriptive statistics for outcomes by sex
- Analyze primary safety and effectiveness endpoints by sex
- Investigate clinically meaningful sex differences
- Include sex-specific information in labeling and marketing applications
- Consider barriers to enrollment and implement strategies to enhance participation
- Evaluate need for sex-specific claims or additional data collection
- Monitor enrollment demographics throughout the study
- Consult with FDA if significant sex differences are observed
Key Considerations
Clinical testing
- Enroll proportions of women and men consistent with disease prevalence
- Consider sex differences in disease etiology and pathophysiology
- Investigate potential sex differences in safety and effectiveness outcomes
- Power studies appropriately if sex-specific differences are anticipated
- Consider sex-specific analyses in study design and statistical analysis plan
Human Factors
- Consider barriers to enrollment of women in clinical studies
- Address family responsibilities limiting study participation
- Provide flexibility in follow-up scheduling
- Consider providing childcare during appointments
Labelling
- Report enrollment demographics by sex
- Include sex-specific outcomes analyses in labeling
- Report clinically meaningful sex differences in safety or effectiveness
- Describe sex-specific baseline characteristics and comorbidities
- Include sex-specific information in summaries of safety and effectiveness
Safety
- Analyze primary safety endpoints by sex
- Report sex-specific adverse events
- Investigate potential sex differences in safety outcomes
- Consider sex-specific safety signals for additional evaluation
Other considerations
- Consider anatomical differences between sexes
- Evaluate potential confounding factors correlated with sex
- Assess treatment by sex interactions in comparative studies
- Consider separate reference intervals/cutoffs for diagnostic devices if needed
- Control Type 1 error rates for sex-specific claims
Relevant Guidances 🔗
- Collection and Reporting of Race and Ethnicity Data in Clinical Trials
- Design Considerations for Medical Device Pivotal Clinical Studies
- Benefit-Risk Determinations for Medical Device Premarket Review
- Patient Engagement in Medical Device Clinical Studies: Roles, Benefits and Best Practices