ides in a new device space: an fda view of mitral john laschinger, md cdrh, ode, dcd, shdb...
TRANSCRIPT
IDEs in a New Device Space:
An FDA View of Mitral
John Laschinger, MD CDRH, ODE, DCD, SHDB
Predictable And SuStainable Implementation Of National Registries For Cardiovascular Devices
Key Issues to Consider
Registry Use in MV IDE Trials
• Applying Lessons learned from TAVR
• US Regulatory realities– Pre-Market– Post-Market • Sustainable model for
success utilizing Registries
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Clinical Considerations
What Currently Works Well – Lessons form TAVR
FLEXABILITY – Tailor Trials
• New Device for New Use (TMVR)Strategy trial vs. established SOC
• New Device for Established Use New Device Approval
• Iteration of Approved DeviceIterative Device Approval
• Old Device for New Use Label Expansion – Anchors, Access & populations
• Staged Pre-Clinical Testing• Standardized Outcome
Measures • 30 day Safety Composites• Time-Insensitive Effectiveness
Composites• Benchmark Outcomes –
Early PG
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What Currently Doesn’t Work Well – US Device Lag
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•Pre-Clinical Studies •Clinical Studies•FIH•Feasibility•Pivotal
•Other
EVIDENCEData Acquisition and
Analysis
•Evidence •Quality and Integrity•Quantity
UNCERTAINTY around the evidence
• Scientific Judgment
BETTERREGULATORY
DECISIONS
•Post-Market Data•Post market studies•MDR’s•Harmonized Registries
•Case for Quality Initiative•Design and Production
POST-MARKET REGISTRY
SURVEILLANCE
Changing the Pre – Post Market Balance
CDRH InitiativesPre-post Market BalanceExpedited Access PMA
Post-Market Surveillance
Short Term Goals: Optimizing Pre-Market Data
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Long Term Goals – Attracting Sponsors to the US
Enhanced Post-MarketSurveillance
Steps:• Early Entry: FIH and
EFS• Rapid Transitions
• Tailored Data Requirements
• Standardized Outcomes Measures
• “Staged” Trial Design
FIM EFS (30 d) Pivotal
JIT Pre-Clinical TestingStandardized Outcomes
Performance GoalsTailored Trials
Pre-Post Market Balance
Early Device
ApprovalU.S. EFS
(30d S & E)
Optimizing Data and Time
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Tiered Certification – Device Development
Enhancing the Value of Registries - SUSTAINABILITY
*Research Infrastructure /expertise for Pivotal Trials Full dataset capabilities: 0- 30-day to 1-5 year
Premarket uses – Essential for sustainability and industry support• Assurance of high quality reliable data• Recognition that capabilities of participants vary
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RisksHarmful eventsDevice: • Unsafe• Ineffective Benefits
Earlier Patient AccessAlternatives:• Absent• Limited use
Robust National
Medical Device Post-market Surveillance
System
Striking the Right Balance – Essential Role of Registries
Closing the Gap - Minimizing Pre-Market Data
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Robust
Accurate - real-world performance Timely
Quickly identifies• poorly performing devices • need for new or improved devices
Transparent Patients and Physicians Payors Regulators Industry
Facilitate device approval or clearance Reliable and Sustainable Registries
Requirements For an Effective Post-Market Registry
Information needed to make well-informed decisions
Closing the Gap - Minimizing Pre-Market Data
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Acute Device Safety Performance Goals - Future:• Risk population based• Individual or Composite 30 day MAE rates
for:– Mortality – Stroke– Paravalvular leak > 1+– Major Vascular Injury– Life Threatening Bleeding– AKI Grade 3– New Pacemaker/LBBB– Coronary Occlusion/MI– Urgent/Emergent OR
Safety: Timing and Performance Goals
• First Steps - We have developed Standard Outcomes for 30 day
Safety!Standardized 30 day Safety Composite:• Non-hierarchical composite • Includes:
• all-cause mortality,• disabling stroke, • life threatening bleeding,• acute kidney injury
requiring dialysis• major vascular
complications
Minimizing Pre-Market Data - Outcome Standardization
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Effectiveness: Timing and Performance Goals
Device Success:• Disabling Stroke free survival• Original/Intended device in place• No Additional valve/access related procedures• No paravalvular Complications (e.g. PPM,
Coronary occlusion, PVL > mild)• Intended performance of valve
‒ Gradient < 5mmHg, EOA > 1.5cm2
‒ MR < 2+‒ No hemolysis, fracture, migration,
endocarditis or thrombosis
• We have developed clinically meaningful composite measures of effectiveness that are time insensitive*
* Can be determined at any time point post procedure – followed post-market over time
Individual Patient Success:Device success AND
• No re-hospitalizations for HF or treated valve related causes
• NYHA class ≤ 2, or improvement in NYHA class by at least 1 level from baseline
• 6MWT >50 meter increase vs. baseline• KCCQ improvement by > 10 vs. baseline
Minimizing Pre-Market Data - Outcome Standardization
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Closing the Gap: Time to ApprovalNo Control Over Quality/Quantity of Early Data
Out of Our Control!
CE Mark
IDE Approval
FIM and EFS OUS DATA
Safety and Performance
≈Sufficient Safety to
initiate a clinical trial
Current Reality
TIME
PMA ApprovalSafety and Effectiveness
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CE Mark
IDE Approval
FIM and EFS OUS DATA
Safety and Performance
≈Sufficient Safety to
initiate a clinical trial
Current Regulatory Reality
TIMEPMA ApprovalSafety and Effectiveness
No Control Over Quality/Quantity of Early Data
Out of Our Control!
Time to Device Approval: US vs. EU
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Getting better Data Earlier
CE Mark
PMA Approval
US FIM /EFS PIVOTAL DATA
Safety and Performance
Getting Control:More Data Better Data
Earlier
Safety and Effectiveness
Closing the Gap: Time to Approval
Changing Reality
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Discussion