Benefit-Risk Determinations for Medical Device Premarket Review
This guidance explains the principal factors that FDA considers when making benefit-risk determinations in the premarket review of medical devices subject to premarket approval (PMA) applications or De Novo classification requests. It applies to both diagnostic and therapeutic devices, and the concepts are applicable throughout the medical device development process from design to market.
What You Need to Know? 👇
What are the key factors FDA considers when making benefit-risk determinations for medical devices?
FDA evaluates the extent of probable benefits (type, magnitude, probability, duration), extent of probable risks (severity, rates, probability, duration), uncertainty levels, patient perspectives, availability of alternatives, risk mitigation strategies, and potential for postmarket data collection to ensure reasonable assurance of safety and effectiveness.
How does FDA assess the benefits of a medical device during premarket review?
FDA assesses benefits by examining the type of benefit (clinical management impact, patient health improvement), magnitude of benefit (scale of improvement), probability of patients experiencing benefits, and duration of effects. Benefits are measured through validated endpoints, surrogate measures, or clinical performance characteristics.
What types of risks does FDA evaluate for medical device approval?
FDA evaluates device-related serious and non-serious adverse events, procedure-related complications, probability and duration of harmful events, false-positive/false-negative results for diagnostics, and considers the aggregate effect when multiple harmful events occur simultaneously in patients.
How does patient preference information influence FDA’s benefit-risk decisions?
Patient preference information helps FDA understand patient willingness to accept risks for probable benefits. This includes qualitative or quantitative assessments of treatment acceptability, consideration of disease severity and chronicity, and evaluation of how patients view trade-offs between benefits and risks.
What role does uncertainty play in FDA’s medical device benefit-risk assessments?
Uncertainty affects the degree of confidence in benefits and risks. FDA considers factors like study design quality, data reliability, generalizability to intended populations, and validation of analytical approaches. Higher uncertainty may require additional risk mitigation or postmarket studies.
How can manufacturers mitigate risks to improve their device’s benefit-risk profile?
Risk mitigation strategies include appropriate labeling with warnings and precautions, restricting use to qualified healthcare providers, requiring specialized training programs, implementing device tracking, and establishing postmarket surveillance or post-approval studies to monitor long-term performance.
What You Need to Do 👇
Recommended Actions
- Document and assess the extent of probable benefits including:
- Type of benefits
- Magnitude of benefits
- Probability of experiencing benefits
- Duration of effects
- Document and assess the extent of probable risks including:
- Severity and types of harmful events
- Probability of harmful events
- Duration of harmful events
- Risks from false results for diagnostics
- Consider additional factors in benefit-risk assessment:
- Characterize uncertainty in benefits and risks
- Evaluate patient perspectives and preferences
- Assess available alternatives
- Identify risk mitigation strategies
- Consider postmarket data needs
- Use the provided worksheet to document benefit-risk determinations systematically
- Ensure transparency in benefit-risk decisions through clear documentation
- Consider early interaction with FDA review division when developing patient preference data
- For novel technologies, assess if greater uncertainty may be acceptable given unmet medical need
- Document risk management decisions according to ISO 14971 requirements
- Consider postmarket studies when appropriate to further characterize benefits and risks
- Ensure labeling clearly communicates benefits and risks to users
Key Considerations
Clinical testing
- Clinical testing methods can include randomized clinical trials, well-controlled investigations, partially controlled studies, case histories, and testing on clinical specimens
- Both clinical and non-clinical data play important roles in benefit-risk determinations
- FDA relies on valid scientific evidence in making risk and benefit determinations
Non-clinical testing
- Can include performance testing for safety/reliability/characterization, human factors testing, animal studies, computer simulations
- Tests mechanical, electrical and chemical properties including wear, strength, biocompatibility, EMC, sterility, stability, software validation
- Non-clinical data can be critical for understanding device safety and effectiveness
Safety
- FDA assesses severity, types, number and rates of harmful events
- Considers device-related serious and non-serious adverse events
- Evaluates procedure-related complications
- Assesses probability and duration of harmful events
- For diagnostics, considers risks from false positives/negatives
Other considerations
- Patient perspectives and preferences regarding benefits and risks
- Availability of alternative treatments/diagnostics
- Risk mitigation strategies
- Novel technology addressing unmet medical need
- Uncertainty in benefit-risk assessment
- Postmarket data collection when appropriate
- Disease characterization and natural history
Relevant Guidances 🔗
- Benefit-Risk Assessment with Uncertainty in Medical Device Premarket Submissions
- Patient Preference Information in Medical Device Development, Clinical Trials, and Regulatory Decision Making
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Design Controls for Medical Device Manufacturers
Related references and norms 📂
- ISO 14971: Medical devices - Application of risk management to medical devices