Benefit-Risk Factors in IDE Applications for Medical Device Clinical Investigations

What You Need to Know? 👇

What are the key factors FDA considers when evaluating IDE applications for medical devices?

FDA evaluates risks to study subjects, anticipated benefits, disease severity, available alternatives, uncertainty levels, and risk mitigation measures. The assessment considers the stage of device development and requires that risks don’t outweigh anticipated benefits and knowledge gained.

How does the benefit-risk assessment differ between early feasibility and pivotal IDE studies?

Early feasibility studies accept greater uncertainty and focus on controlling anticipated possible risks, while pivotal studies emphasize mitigating the most probable risks. Earlier stages require appropriate risk controls for novel technologies with limited clinical data.

What risk mitigation measures can sponsors implement to improve IDE approval chances?

Sponsors can implement safety by design features, protective measures (staged enrollment, specialized sites, monitoring committees), study design modifications, enhanced reporting requirements, and comprehensive communication of safety information to subjects and investigators.

When can FDA disapprove an IDE application under current regulations?

FDA may disapprove if risks outweigh anticipated benefits and knowledge gained, informed consent is inadequate, the study is scientifically unsound, there’s non-compliance with regulations, or inadequate manufacturing controls, monitoring, or prior investigation reports.

How should sponsors address uncertainty in IDE applications for novel medical devices?

Sponsors should acknowledge uncertainty levels appropriate to development stage, provide quality prior investigations, demonstrate predictive capability of evidence, implement staged approaches for high uncertainty, and apply comprehensive risk control measures throughout the study.

What constitutes adequate informed consent for IDE studies involving significant risks?

Informed consent must describe reasonably foreseeable risks, provide adequate study information including device risks and benefits, allow sufficient consideration time, minimize coercion, and enable subjects to make informed decisions about accepting potential risks.

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What You Need to Do 👇

Recommended Actions

1. Develop comprehensive risk management plan including:
   • Risk analysis
   • Risk control measures
   • Residual risk evaluation
2. Prepare detailed device description including:
   • Device identification
   • Principle of operation
   • Key specifications
   • Materials
   • Software/hardware features
3. Design appropriate study oversight mechanisms:
   • IRB review
   • Data monitoring committee
   • Adverse event reporting procedures
4. Implement robust informed consent process with:
   • Clear risk communication
   • Description of benefits
   • Study requirements
5. Establish investigator/site requirements:
   • Training requirements
   • Experience criteria
   • Resource capabilities
6. Create monitoring plan with:
   • Safety assessments
   • Data collection procedures
   • Reporting timelines
7. Document benefit-risk assessment addressing:
   • Context of investigation
   • Risk assessment
   • Benefit assessment
   • Patient preferences
   • Uncertainty evaluation
8. Ensure compliance with:
   • IDE regulations
   • Human subject protection requirements
   • Study monitoring requirements
   • Records and reporting requirements

Key Considerations

Clinical testing

• Clinical investigations must comply with informed consent requirements under 21 CFR part 50
• Study design should be scientifically sound and generate useful knowledge
• Study oversight through IRB, Clinical Events Committee, Data Monitoring Committee required
• Frequent follow-up assessments to monitor subject safety and device effectiveness
• Timely reporting of serious adverse events
• Pre-specified plan for periodic participant outcome assessments

Non-clinical testing

• Quality of prior nonclinical investigations important to reduce uncertainty
• Non-clinical testing can complement or replace need for clinical testing in some cases
• Biocompatibility and other safety testing should be completed before clinical studies
• Animal studies may be needed to evaluate procedural risks

Human Factors

• Implementation of informed consent process that adequately conveys risks and benefits
• Plan to capture human factors information during study to modify procedures/device as needed
• Identification of qualified investigators with adequate training
• Use of specialized/experienced study sites

Labelling

• Must be labeled for investigational use only
• Communication of safety information to study subjects about foreseeable risks
• Clear communication among study sites regarding safety information
• Adequate informed consent documents

Biocompatibility

• Biocompatibility testing required before clinical studies
• New materials need to be fully characterized
• Assessment of degradation products for absorbable devices

Safety

• Basic safety protection against physical hazards must be addressed
• Risk management plan required including:
  • Risk analysis
  • Risk control measures
  • Residual risk evaluation
• Safety monitoring and reporting requirements
• Pre-specified stopping rules

Other considerations

• Patient preferences should be considered when available
• Disease/condition characteristics impact benefit-risk assessment
• Alternative treatment availability affects acceptable risk levels
• Different uncertainty considerations at different stages of development
• Study design should be least burdensome while maintaining scientific validity

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Relevant Guidances 🔗

• Applying Human Factors Engineering and Usability Engineering to Medical Devices
• Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
• Design Controls for Medical Device Manufacturers
• Informed Consent in Clinical Investigations: Requirements, Documentation, and Procedures

Related references and norms 📂

• ANSI/AAMI/ISO 14971: Medical Devices - Application of risk management to medical devices

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Original guidance

• Benefit-Risk Factors in IDE Applications for Medical Device Clinical Investigations
• HTML / PDF
• Issue date: 2017-01-13
• Last changed date: 2020-10-20
• Status: FINAL
• Official FDA topics: Medical Devices, Premarket, Biologics, Investigational Device Exemption (IDE), Clinical - Medical
• ReguVirta ID: 5f40212d68ca38061e938b0bba011ef0