Clinical Study Design and Benefit-Risk Considerations for Weight Loss Medical Devices (DRAFT)
This guidance provides recommendations for clinical study design and benefit-risk considerations for medical devices with indications associated with weight loss, including weight loss, weight reduction, weight management, or obesity treatment in patients who are overweight or have obesity.
This is a draft guidance. Not for implementation.
What You Need to Know? 👇
What are the key clinical study design requirements for medical devices with weight loss indications?
FDA recommends double-blinded, randomized controlled trials with sham controls when appropriate. Studies should include co-primary effectiveness endpoints: superiority margin for mean %TBWL and responder rate (≥50% achieving ≥5% TBWL). Duration should be ≥12 months for “weight loss” indications.
How does FDA classify adverse events for weight loss devices using the modified Clavien-Dindo system?
The classification grades adverse events I-V based on treatment required: Grade I (over-the-counter medications), Grade II (prescription drugs/IV fluids), Grade III (surgical/endoscopic interventions), Grade IV (life-threatening/ICU care), Grade V (death). This standardizes risk assessment across different device types.
What BMI criteria should be used for enrolling patients in weight loss device clinical studies?
For implanted/surgical devices: BMI ≥35 kg/m² or ≥30 kg/m² with weight-related comorbidities. Lower-risk devices may include BMI ≥27 kg/m² with comorbidities. Higher-risk devices may require additional BMI specifications to ensure anticipated benefits outweigh probable risks.
What are the special considerations for pediatric weight loss device studies?
Devices shouldn’t be studied in pediatrics until adult data shows ≤minimal risk. Use CDC BMI-for-age percentiles for classification. Include lead-in periods, comprehensive weight management program failure documentation, and specialist psychological assessment. Primary endpoints should consider linear growth patterns.
How does FDA evaluate benefit-risk for weight loss devices using the Evaluation Matrices?
FDA uses four matrices corresponding to weight loss categories (short-term limited, limited, short-term, and weight loss) plotted against adverse event grades. Cell shading indicates favorable (white), uncertain (light gray), or unfavorable (dark gray) profiles, with darkest cell determining overall assessment.
What foreign data limitations apply to weight loss device clinical studies?
FDA recommends ≤50% of pivotal study data from outside US due to cultural and policy impacts on weight loss outcomes. No more than 20% enrollment from single site to prevent outcome bias. Foreign data must meet 21 CFR 812.28 requirements for FDA acceptance.
What You Need to Do 👇
Recommended Actions
- Develop comprehensive clinical study protocol addressing:
- Study design and controls
- Patient selection criteria
- Duration and follow-up schedule
- Primary and secondary endpoints
- Adverse event monitoring and classification
- Statistical analysis plan
- Establish data safety monitoring board and endpoint adjudication committee
- Implement robust adverse event tracking system using modified Clavien-Dindo classification
- Create detailed plan for documenting and analyzing:
- Weight loss metrics (% TBWL, BMI changes)
- Adverse events and complications
- Device removals
- Patient-reported outcomes
- Consider submitting Q-Submission to FDA to discuss study design before implementation
- For pediatric studies, develop additional safeguards and monitoring procedures
- Use evaluation matrices to assess benefit-risk profile based on weight loss and adverse events
- Document all aspects needed for benefit-risk determination including:
- Clinical benefits (weight loss, comorbidity changes)
- Device and procedure risks
- Patient preference information
- Alternative treatment options
Key Considerations
Clinical testing
- Pivotal studies should be double-blinded, randomized, controlled trials (RCTs)
- Sham-controlled study recommended due to anticipated placebo effect
- No more than 50% of pivotal study data should be collected outside US
- Study duration and follow-up should be adequate based on indication:
- “Weight loss”: 12 months or more
- “Short term weight loss”: 6-12 months
- “Weight management”: less than 6 months
- Co-primary effectiveness endpoints recommended:
- Superiority margin of mean % total body weight loss over control
- Performance goal for responder rate based on individual subject success
Safety
- Adverse events should be classified using modified Clavien-Dindo system based on treatment required
- Data safety monitoring board (DSMB) recommended
- Independent endpoint assessment/adjudication committee recommended
- Document all adverse events and categorize as device-related, procedure-related, or not related
- Tabulate serious adverse events and unanticipated adverse device effects
- Document time to onset and duration of GI-related adverse events
- Track all unanticipated device removals and reasons
Other considerations
- For pediatric studies:
- Device should not be studied until adult data shows minimal risk
- Risk of permanent implant removal should be well defined
- Document history of failing lifestyle modification
- Include lead-in period to assess compliance
- Study duration minimum 12 months for permanent devices
- Screen for genetic causes of obesity
- Assess maturity level and psychosocial factors
Relevant Guidances đź”—
- Non-Clinical Testing Recommendations for Weight Loss and Obesity Treatment Devices (Draft)
- Design Considerations for Medical Device Pivotal Clinical Studies
- Benefit-Risk Determinations for Medical Device Premarket Review
- Patient Preference Information in Medical Device Development, Clinical Trials, and Regulatory Decision Making
Related references and norms đź“‚
- ISO 14155: Clinical investigation of medical devices for human subjects - Good clinical practice