Design Considerations for Medical Device Pivotal Clinical Studies
This guidance provides recommendations for designing pivotal clinical studies intended to support pre-market submissions for medical devices. It focuses on two broad categories of devices: therapeutic/aesthetic devices and diagnostic devices. The guidance aims to help sponsors and investigators design studies that can demonstrate reasonable assurance of safety and effectiveness for device approval. While primarily focused on PMAs, the principles can also apply to 510(k) and de novo submissions with clinical data.
Recommended Actions
- Develop robust exploratory/feasibility studies before pivotal study
- Create detailed protocol including:
- Scientific rationale
- Study population definition
- Endpoints
- Statistical analysis plan
- Data management plan
- Consider pre-submission meeting with FDA to discuss study design
- Implement appropriate bias minimization strategies:
- Randomization when possible
- Blinding when possible
- Appropriate controls
- Multi-center design
- Ensure study population reflects intended use population
- Develop monitoring plan to maintain data quality
- Pre-specify handling of protocol deviations and missing data
- Document human factors considerations and training requirements
- Plan for appropriate safety monitoring
- Consider need for independent monitoring committee
Key Considerations
Clinical testing
- Studies must provide reasonable assurance of safety and effectiveness for the intended use
- Study design should minimize bias and control variability
- Pivotal studies should be preceded by exploratory/feasibility studies
- Study population should reflect intended use population demographics
- Multi-center studies preferred over single-center for pivotal studies
- Randomization and blinding recommended when possible
- Appropriate controls should be selected (active, placebo, no intervention, etc.)
Human Factors
- User skill level and training requirements must be considered
- Learning curve should be evaluated and documented
- Human factors can impact device safety and effectiveness
- Clear documentation of device-user interface needed
Safety
- Safety and effectiveness must be evaluated together
- Risk-benefit assessment required
- Safety endpoints should be pre-specified
- Adverse events must be monitored and reported
Other considerations
- Data management plan recommended
- Statistical analysis plan should be pre-specified
- Protocol deviations should be minimized and documented
- Missing data should be minimized through study design
- Changes to pivotal study should be minimized
- Independent monitoring recommended for some studies
Relevant Guidances
- Applying Human Factors Engineering and Usability Engineering to Medical Devices
- Content and Decision-Making Process for 510k Submissions: Determining Substantial Equivalence
- De Novo Classification Process for Novel Medical Devices Without Predicates
- Benefit-Risk Determinations for Medical Device Premarket Review
- Statistical Guidance for Reporting Diagnostic Test Results with Qualitative Outcomes
Related references and norms
- ISO 14155:2011: Clinical investigation of medical devices for human subjects - Good clinical practice
Original guidance
- Design Considerations for Medical Device Pivotal Clinical Studies
- HTML / PDF
- Issue date: 2013-11-07
- Last changed date: 2023-08-10
- Status: FINAL
- Official FDA topics: Medical Devices, Good Clinical Practice (GCP), Premarket, Biologics, Investigational Device Exemption (IDE)
- ReguVirta summary file ID: 676ed951eefcaca3cf592d9314fee671
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