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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.

  1. Develop robust exploratory/feasibility studies before pivotal study
  2. Create detailed protocol including:
    • Scientific rationale
    • Study population definition
    • Endpoints
    • Statistical analysis plan
    • Data management plan
  3. Consider pre-submission meeting with FDA to discuss study design
  4. Implement appropriate bias minimization strategies:
    • Randomization when possible
    • Blinding when possible
    • Appropriate controls
    • Multi-center design
  5. Ensure study population reflects intended use population
  6. Develop monitoring plan to maintain data quality
  7. Pre-specify handling of protocol deviations and missing data
  8. Document human factors considerations and training requirements
  9. Plan for appropriate safety monitoring
  10. 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

  • 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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