Adaptive Designs for Medical Device Clinical Studies
This guidance addresses adaptive designs for medical device clinical studies, applicable to premarket medical device submissions including PMA, 510(k), de novo, HDE and IDE submissions. An adaptive design allows for prospectively planned modifications based on accumulating study data without undermining the study's integrity and validity. The guidance covers both feasibility and pivotal clinical studies but does not apply to combination products or co-development of pharmaceutical products with diagnostic tests.
Recommended Actions
- Determine if adaptive design is feasible and advantageous for your specific study
- Develop detailed prospective plan for adaptations including:
- Statistical analysis plan
- Operating characteristics
- Decision rules
- Monitoring procedures
- Firewall implementation
- Establish appropriate oversight including:
- Data Monitoring Committee if using unblinded data
- IRB review procedures
- Monitoring plan specific to adaptive aspects
- Engage with FDA through pre-submission process to discuss adaptive design strategy
- Document thoroughly:
- Adaptation implementation
- Maintenance of study integrity
- Data before and after adaptations
- Any deviations from planned adaptations
- Implement robust infrastructure for:
- Data management
- Information access control
- Communication procedures
- Supply chain management
- Prepare final study documentation including:
- Description of adaptation implementation
- Complete datasets
- Pre-specified statistical analyses
- Documentation of any deviations
Key Considerations
Clinical testing
- Adaptations must be prospectively planned and described in protocol before study initiation
- Changes based on unblinded data require careful planning and statistical considerations
- Need to control Type I error rate and maintain adequate power
- Need to assess homogeneity of results before and after modifications
- DMC oversight recommended for adaptive designs using unblinded data
Safety
- Adaptive designs can be used for safety endpoints
- Early stopping rules for safety can be incorporated
- DMC should monitor safety throughout adaptive trials
Other considerations
- Need robust infrastructure to implement adaptive designs appropriately
- Must minimize operational bias through firewalls and blinding procedures
- IRB oversight and informed consent must reflect adaptive nature of study
- Detailed documentation of adaptation implementation required
- Pre-submission interaction with FDA recommended
- Need monitoring plan focused on adaptive design aspects
Relevant Guidances
- Design Controls for Medical Device Manufacturers
- Design Considerations for Medical Device Pivotal Clinical Studies
- Statistical Guidance for Reporting Diagnostic Test Results with Qualitative Outcomes
- Bayesian Statistics in Medical Device Clinical Trials: Design, Analysis and Implementation
Related references and norms
- ISO 14155: Clinical investigation of medical devices for human subjects - Good clinical practice
Original guidance
- Adaptive Designs for Medical Device Clinical Studies
- HTML / PDF
- Issue date: 2016-07-27
- Last changed date: 2020-10-20
- Status: FINAL
- Official FDA topics: Medical Devices, Good Clinical Practice (GCP), Premarket Approval (PMA), Premarket, Biologics, HUD/HDE, Investigational Device Exemption (IDE)
- ReguVirta summary file ID: a9d7a8cd59dc49fe20444b10b3191a8d
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