Benefit-Risk Assessment with Uncertainty in Medical Device Premarket Submissions
This guidance describes FDA's approach to considering uncertainty in benefit-risk determinations for medical device premarket approval applications (PMAs), De Novo requests, and humanitarian device exemption (HDE) applications. It aims to promote public health by helping patients have timely access to new medical devices while ensuring they meet applicable statutory standards for safety and effectiveness.
Recommended Actions
- Evaluate factors affecting acceptable uncertainty level for your device
- Consider if your device qualifies for greater uncertainty acceptance (breakthrough or small population)
- Design appropriate premarket clinical studies based on acceptable uncertainty level
- Develop robust postmarket data collection plan if needed
- Prepare labeling that appropriately communicates uncertainty and postmarket data collection
- Consider using real-world data sources for postmarket evidence generation
- Engage early with FDA through Q-submission process to discuss development program
- Document benefit-risk assessment considering all relevant factors
- Plan for timely postmarket data collection if required
- Prepare for potential advisory committee review of postmarket data
Key Considerations
Clinical testing
- Clinical evidence requirements are flexible and tailored to the device
- Greater uncertainty may be accepted for breakthrough devices and devices for small populations
- Postmarket data collection may be required to address uncertainty
- Sample size requirements may vary based on accepted level of uncertainty
Non-clinical testing
- Non-clinical performance data can provide essential information on safety and effectiveness
- Can inform clinical trial design and extent of premarket evidence needed
- Can include bench studies, animal studies, and computational modeling
Labelling
- May need to include information about postmarket data collection and its purpose
- Should be updated when additional postmarket data supports changes
Safety
- Must demonstrate reasonable assurance of safety
- Risk mitigation measures should be considered
- Uncertainty in safety profile must be balanced against benefits
Other considerations
- Patient perspective on uncertainty should be considered
- Public health need impacts acceptable level of uncertainty
- Feasibility of generating extensive clinical evidence
- Ability to reduce uncertainty postmarket
- Type of regulatory decision being made
- Benefits of earlier patient access
Relevant Guidances
- Benefit-Risk Determinations for Medical Device Premarket Review
- Balancing Pre-Market and Post-Market Data Collection for PMA Medical Devices
- Breakthrough Devices Program: Expedited Development and Review Process for Novel Medical Devices
- Humanitarian Device Exemption (HDE) Program: Operational Requirements and Benefit-Risk Assessment
- Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program
- Use of Real-World Data to Generate Evidence for Medical Device Regulatory Decisions
Related references and norms
- 21 CFR 860.7: Determination of Safety and Effectiveness
- 21 CFR 814.82: Postapproval Requirements
Original guidance
This post is licensed under CC BY 4.0 by the author.