Clinical Trial Considerations for Neurological Devices Intended to Slow, Stop, or Reverse Disease Progression

Recommended Actions

1. Submit Pre-Submission to FDA to discuss study design and endpoints
2. Develop comprehensive investigational plan including all study phases
3. Establish both biomarker tests and clinical outcome assessments
4. Create detailed safety monitoring and reporting protocol
5. Perform thorough benefit-risk analysis
6. Prepare compliant informed consent documents
7. Develop labeling that accurately reflects study conditions and results
8. Consider early-stage disease populations for studying progression
9. Plan for long-term follow-up to evaluate treatment effects
10. Establish clear protocols for adverse event reporting and risk mitigation

Key Considerations

Clinical testing

• Studies should distinguish between symptomatic benefits and disease-altering benefits
• Need to include both biomarker tests and clinical outcome assessments
• Clinical outcome assessments should measure direct quantitative effects on disease progression
• Studies may need to be prolonged to understand disease progression
• Need to incorporate or compare to standard care regimens
• Early engagement with FDA through Pre-Submission process recommended

Labelling

• Must comply with 21 CFR 812.5
• Should identify intended patient population
• Must describe all relevant hazards, adverse effects, warnings and precautions
• Should alert users to potentially injurious outcomes
• Should be consistent with how device was studied

Safety

• Need to capture surgical complications and perioperative events
• Need long-term adverse event monitoring
• Clear protocol for reporting adverse events to DSMB, IRB and FDA
• Risk analysis required including risk mitigation steps
• Define acceptable levels for probable and serious adverse events

Other considerations

• Benefit-risk framework should be used
• Patient preferences and risk tolerance vary
• Assessment against commonly used therapies rather than most advanced alternatives
• Early interaction with FDA review division recommended
• Informed consent must comply with 21 CFR 50.25

  Relevant Guidances

• Benefit-Risk Factors in IDE Applications for Medical Device Clinical Investigations
• IDE Clinical Investigation Decision Process and Requirements
• Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program
• Informed Consent in Clinical Investigations: Requirements, Documentation, and Procedures

Related references and norms

• 21 CFR 812: Investigational Device Exemptions
• 21 CFR 50: Protection of Human Subjects
• 21 CFR 56: Institutional Review Boards

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Original guidance

• Clinical Trial Considerations for Neurological Devices Intended to Slow, Stop, or Reverse Disease Progression
• HTML / PDF
• Issue date: 2016-11-07
• Last changed date: 2019-02-14
• Status: FINAL
• Official FDA topics: Laser Notice, Medical Devices, Good Clinical Practice (GCP), Errors, and Problems, Premarket Approval (PMA), 510(k), Premarket, Labeling, HUD/HDE, Advisory Committees, Safety - Issues, Clinical - Medical, Neurological
• ReguVirta summary file ID: c169eb57b4a335e4741022abd8afd1c7