Clinical Trial Considerations for Neurological Devices Intended to Slow, Stop, or Reverse Disease Progression
This guidance applies to neurological medical devices designed to slow, stop, or reverse disease progression and achieve meaningful clinical outcomes. It provides study design considerations for clinical trials using biological markers and clinical outcome assessments.
What You Need to Know? 👇
What are the key differences between biomarkers, intermediate endpoints, and surrogate endpoints in neurological device trials?
Biomarkers objectively measure biological processes or therapeutic responses. Intermediate endpoints are clinical measures of symptoms or function that have value to patients but aren’t ultimate outcomes. Surrogate endpoints substitute for clinical endpoints and are expected to predict clinical outcomes based on scientific evidence.
How should sponsors design clinical trials to distinguish between symptomatic benefits and disease-altering effects?
Study designs should incorporate both biomarker tests and clinical outcome assessments measured at appropriate intervals. Trials should compare investigational devices to standard care regimens and use controls like delayed time-to-treatment to differentiate symptomatic improvements from actual disease progression modification.
What specific elements must be included in informed consent documents for neurological device studies?
Informed consent must describe the possibility that treatment may have little or no effect on disease progression or could worsen it, options for discontinuing study participation, and the potential need for long-term follow-up to evaluate treatment effects.
When should sponsors engage with FDA for neurological devices targeting disease progression?
FDA strongly recommends early engagement through the Pre-Submission process before conducting clinical trials. This facilitates discussion of preclinical protocols, clinical trial designs, and proposed indications for use, especially given the complex nature of neurological disease progression studies.
What safety considerations are particularly important for neurological device IDE applications?
Safety protocols must capture surgical complications, perioperative and long-term adverse events. Studies require clearly delineated protocols for reporting adverse events to Data Safety Monitoring Boards, IRBs, and FDA, plus risk analysis with mitigation steps and acceptable adverse event levels.
How does FDA evaluate benefit-risk for neurological devices in early disease stages?
FDA uses a comprehensive benefit-risk framework considering that patients may forgo approved treatments for potentially more invasive interventions. Assessment considers individual patient risk tolerance, disease nature, available treatments, and the significant potential long-term benefit of slowing disease progression.
What You Need to Do 👇
Recommended Actions
- Submit Pre-Submission to FDA to discuss study design and endpoints
- Develop comprehensive investigational plan including all study phases
- Establish both biomarker tests and clinical outcome assessments
- Create detailed safety monitoring and reporting protocol
- Perform thorough benefit-risk analysis
- Prepare compliant informed consent documents
- Develop labeling that accurately reflects study conditions and results
- Consider early-stage disease populations for studying progression
- Plan for long-term follow-up to evaluate treatment effects
- 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
- Q-Submission Program: Strategic Framework for FDA Interactions in Medical Device Development
- 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
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 ID: c169eb57b4a335e4741022abd8afd1c7