Clinical Study Design for Surgical Ablation Devices Used in Treatment of Atrial Fibrillation Under Direct Visualization
This guidance addresses clinical study design for surgical ablation devices intended for the treatment of atrial fibrillation (AF) under direct visualization. It applies to new surgical ablation devices and legally marketed devices seeking a new AF treatment indication. The guidance specifically excludes cardiac ablation devices not used under direct visualization and those delivered intravascularly.
Recommended Actions
- Design a randomized controlled trial with 12-month follow-up period
- Develop detailed protocols for:
- Patient selection criteria
- Anticoagulation management
- Follow-up visits and monitoring
- Adverse event reporting
- Establish an independent Clinical Events Committee
- Create investigator training program
- Implement standardized neurological assessments
- Define clear primary effectiveness and safety endpoints
- Develop statistical analysis plan including sample size justification
- Create detailed documentation procedures for all study aspects
- Establish quality monitoring procedures
- Plan for potential post-approval studies with extended follow-up
Key Considerations
Clinical testing
- Randomized controlled trials (RCTs) are recommended as the least burdensome means to develop valid scientific evidence
- 12-month minimum follow-up period required
- Primary effectiveness endpoint should be freedom from AF/AFL/AT for one year without Class I or III antiarrhythmic drugs
- Separate studies recommended for different types of AF (paroxysmal vs persistent)
- Standardized follow-up visits at 30 days, 3, 6, 9 and 12 months
Human Factors
- Investigator selection should be based on qualification and experience
- Training required for investigators lacking thorough knowledge of procedures
- Consider including “roll-in” subjects to avoid learning curve bias
Labelling
- Should identify factors affecting benefit/risk profile:
- Type of AF treated
- Surgical approach used
- Concomitant procedures
- Relevant patient characteristics
Safety
- Primary safety composite endpoint including:
- All-cause death
- Stroke and TIA
- Myocardial infarction
- Thromboembolic events
- Excessive bleeding
- Deep sternal wound infection
- Damage to conduction system requiring pacemaker
- Damage to peripheral structures
- Pulmonary vein stenosis
- Neurological assessment required before and after procedure
- One year safety follow-up recommended
Other considerations
- Clear anticoagulation protocols required
- Antiarrhythmic drug therapy should be discontinued prior to effectiveness evaluation
- Statistical justification needed for sample size calculations
- Independent Clinical Events Committee recommended for adverse events adjudication
Relevant Guidances
- Design Considerations for Medical Device Pivotal Clinical Studies
- Benefit-Risk Factors in IDE Applications for Medical Device Clinical Investigations
- IDE Clinical Investigation Decision Process and Requirements
- Applying Human Factors Engineering and Usability Engineering to Medical Devices
Related references and norms
- NIH Stroke Scale (NIHSS): Standardized scale for assessment of neurologic deficit
- Modified Rankin Score (MRS): Scale for assessment of stroke disability
Original guidance
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