Sex-Specific Considerations in Medical Device Clinical Studies: Patient Enrollment, Data Analysis and Reporting
This guidance outlines FDA's expectations regarding sex-specific patient enrollment, data analysis, and reporting in medical device clinical studies. It applies to devices requiring clinical information for marketing submissions (510(k), PMA, de novo, HDE) and post-approval/surveillance studies. The guidance aims to improve data quality regarding device performance in both sexes by encouraging appropriate enrollment and analysis by sex.
Recommended Actions
- Develop enrollment strategy to achieve appropriate sex representation based on disease prevalence
- Include pre-specified plan for sex-specific analyses in study protocol
- Monitor enrollment demographics and investigate reasons for under-representation
- Conduct analyses of primary endpoints stratified by sex
- Report sex-specific enrollment, baseline characteristics and outcomes in submissions
- Include sex-specific information in device labeling
- Consider post-market studies if sex-specific questions remain unresolved
- Consult with FDA if clinically meaningful sex differences are observed
- Implement retention strategies considering sex-specific barriers to participation
- For diagnostic devices, validate performance in both sexes
Key Considerations
Clinical testing
- Enroll proportions of each sex appropriate to disease prevalence
- Consider sex differences in disease etiology and pathophysiology
- Evaluate sex-specific differences in primary safety and effectiveness endpoints
- Consider powering studies to evaluate treatment effect for both sex groups if clinically meaningful differences are anticipated
Labelling
- Report enrollment demographics by sex
- Include sex-specific outcomes analyses in labeling regardless if pre-specified or post hoc
- Describe covariates that might explain outcome differences between sexes
- Report clinically meaningful sex differences in safety or effectiveness separately for women and men
Safety
- Analyze primary safety endpoints by sex
- Report sex-specific adverse events
- Evaluate potential sex differences in safety outcomes
Other considerations
- Include statistical analysis plan for assessing heterogeneity across sexes
- Consider sex as stratification variable in randomization if differences anticipated
- Investigate reasons for under-enrollment of either sex
- Consider flexibility in follow-up scheduling to improve retention
- For diagnostic devices, include data from both sexes in cutoff selection and validation
Relevant Guidances
- Evaluation of Sex and Gender Differences in Medical Device Clinical Studies (Draft)
- Collection and Reporting of Race and Ethnicity Data in Clinical Trials
- Design Considerations for Medical Device Pivotal Clinical Studies
- Statistical Guidance for Reporting Diagnostic Test Results with Qualitative Outcomes
Related references and norms
- ISO 14155: Clinical investigation of medical devices for human subjects - Good clinical practice
Original guidance
- Sex-Specific Considerations in Medical Device Clinical Studies: Patient Enrollment, Data Analysis and Reporting
- HTML / PDF
- Issue date: 2014-08-22
- Last changed date: 2020-03-02
- Status: FINAL
- Official FDA topics: Medical Devices, Premarket, Good Clinical Practice (GCP)
- ReguVirta summary file ID: 15f96662c136289fc7e549a104588aca
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