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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Thank You!John Laschinger, MD

Medical Officer, SHDB301.796.1210

john.laschinger@fda.hhs.gov

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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