Regulatory Science and Sustainable Implementation of National and International

Medical Device Registries

Focus-- Cardiovascular Registries

TAVR: Case Study on the Value of Collaboration

Ralph Brindis, MD, MPH, MACC, FSCAISenior Medical Officer, ACC-NCDR

March 24, 2014

Disclosure Statement of Financial Interest

Senior Medical Officer, External AffairsACC- NCDR

Salaried Position

The Goals of the TVT Registry

• Learn from patient-level data– Regulatory – device surveillance– Quality improvement

• Insights into patient selection, etc.• Feedback, benchmarking, and best practices at a site

level• Patient education and informed decision-making

– Research – important hypotheses tested to expand our understanding

• Be a driving force in improving our health care system

Does Not Include All TAVR Cases in US• Over 10K Cases from Trials• Some Commercial TAVR Cases Before NCD, VA Cases

All 14,210 Cases are Commercial TAVR288 Sites Enrolled in TVT Registry274 Sites Entering Data6 Sites > 200 Cases; 24 Sites > 100 Cases

No TAVR sites in Alaska and Wyoming

(currently patients served by Seattle

and Colorado sites)

1. As of last week 288 TAVR sites fully enrolled. Additional sites being trained by Edwards and Medtronic will be added.

2. Approximately 43 sites have started commercial MitraClip use are already TAVR-TVT sites.

Sites Participating in TVT Registry (Currently TAVR)

TVT Registry is a Major Collaborative Partnership

TVT Registry

STS

ATS AND SCAI

DCRI

PATIENT ADVOCACY

GROUPS

MEDICAL DEVICE

Companies

NHLBI

CMS

FDA

ACC

Governance

Steering Committee

Research and Publications

Subcommittee

Stakeholder Advisory Group

Data Monitoring

Group

Steering CommitteeSTS Members• Fred Edwards • Fred Grover• Michael Mack• Dave Shahian

Ex Officio Members•FDA - Danica Marinac-Dabic, John Laschinger•CMS - Jyme Schafer•NHLBI - Frank Evans•Chair TVT R&P Subcommittee - John Rumsfeld•DCRI – Eric Peterson

Registry Operations Center• NCDR

ACC Members• Ralph Brindis• John Carroll• David Holmes• Murat Tuzcu

Staff• Cynthia Shewan, Tina Kourtis• Joan Michaels, Kathleen Hewitt,

Barb Christensen

Data Analytics Center• DCRI

Research and Publications Committee

STS Members• Fred Edwards (Co-

Chair)• Vinod Thourani• Jeffrey Jacobs• Todd Dewey

Ex Officio Members•FDA – Art Sedrakyan•Biostats - Eugene Blackstone•DCRI – Eric Peterson•Steering Committee- Murat Tuzcu

Registry Operations Center• NCDR

ACC Members• John Rumsfeld

(Chair)• David Cohen• Neal Kleiman• Ajay Kirtane Staff

• Cynthia Shewan• Mary Weideman• Joan Michaels• Kathleen Hewitt

Data Analytics Center• DCRI, Eric Peterson

STAKEHOLDER ADVISORY GROUP

Society Representatives• John Carroll, MD TVT Registry

Steering Committee liaison • Larry Dean, MD SCAI• Joseph Bavaria, MD AATS • Consumer Representatives• Bray Patrick-Lake PFO Research

Foundation• John Santa, MD Consumer Reports• Fmr. Rep. Tony Coelho Public MemberHealth System and Health Plans • Tom Priselac Cedars-Sinai Hospital

System

Industry Representatives• Chuck Simonton, MD Abbott

Vascular• Larry Wood Edwards Lifesciences• Nusrath Sultana, MD St. Jude Medical• Tom Armitage, MD Medtronic • Keith Dawkins, MD Boston ScientificGovernment Representatives• Bram Zuckerman, MD FDA liaison• John Laschinger, MD FDA liaison• Danica Marinac-Dabic, MD FDA

liaison• Marissa Miller, DVM NIH liaison• Marie Casey CMS liaison

Society Staff RepresentativesCynthia Shewan STS and Joan Michaels ACC

Robert Guyton, MD Chair STS RepresentativeEric Bates, MD Vice-Chair ACC Representative

July 2011

• TVT Registry proposed at FDA Advisory Panel for Edwards Sapien Valve

Nov 2011

• FDA Approves Edwards Sapien THV

Dec 2011

• STS/ACC TVT Registry Launched Version 1.0

May 2012

• CMS issued National Coverage Decision

Feb 2013

• STS/ACC TVT Registry Launched Version 1.2

Sept 2013

• STS/ACC TVT Registry Launched Version 1.3

Oct 25, 2013

• FDA Approves Abbott MitraClip

Jan 17, 2014

• FDA Approves Medtronic CoreValve

May 18,

2014• Anticipated Decision for NCD for MitraClip

May 2014

• STS/ACC TVT Registry Launch for 2.0

STS-ACC TVT RegistryThree Modules in 2.0 Release

Transcatheter Aortic Valve Replacement

• Types• Native• Valve-in-Valve

• Technologies• SapienTM

• CoreValveTM

Transcatheter Mitral Valve Repair

• Types• Direct Leaflet

• Technologies• MitraClipTM

• Future Additions• Annular

Reduction

Transcatheter Mitral Valve Replacement

• Types• Native• Valve-in-Valve• Valve-in-Ring

• Technologies• SapienTM

Relevant Issues• Commercially approved MelodyTM valve in separate NCDR registry• Potential Areas of Expansion in TVT Arena?

• Mitral balloon commissurotomy• Para-prosthetic valve regurgitation repair with transcatheter plugs

TVT Registry Mitral Module

Workgroup CompositionSTS Members• Fred Edwards • Patrick McCarthy• Craig Miller

ACC Members• John Carroll - Chair• Samir Kapadia

STS, DCRI and ACC Staff •Cynthia Shewan and Donna McDonald – STS•Michael Booth and Paul Meehan - DCRI•Joan Michaels and Susan Fitzgerald – ACC ***

Data Analytic Center (DCRI)FDA - John Laschinger***

• FDA• CMS• Industry• ACC and STS

leadership• Analytic Centers• Users (public

comment period)

Echo Specialists• Paul Grayburn ***• Neil Weissman

Heart Failure Specialists• Maggie Redfield • JoAnn Lindenfeld

Stakeholders

Abbott InputBarathi Sethuraman

Bhagya GurusuLiz McDermott

Data Quality!!!! 1. Training and Clinical Support Team

– Orientation webinars– Online FAQs– Live customer support– Email– Monthly webinars– Annual meeting with case reviews, etc.

2. Data Entry Integrity– Software value checks– Field level range parameters– Parent:Child fields

3. Data Completeness– Sites receive completeness reports to resubmit with

missing fields completed– predetermined levels of completeness and consistency

required for data to be included in national and comparison group averages

4. Data Accuracy– Up to 650 records are audited annually.

5. Adjudication of Adverse Events

In the 2010 audits, the overall accuracy of data abstraction for the CathPCI, ICD, and

ACTION-GWTG registries were, respectively, 93.1%, 91.2%, and 90.0%.

JACC June, 2012

Data Quality ProgramPost Submission

Adjudication – Verifies and provides additional information for key

events (stroke, TIA and repeat intervention, plus CHF admission for MitraClip)

National audit program (starts in 2014) – Evaluates accuracy and reliability– Assesses proper and complete reporting of cases– Voluntary and self audits

Data Outlier Program– Provides outlier alerts to Registry participants

Adjudication Process: Additional Data and Physician Review at DCRI

“The FDA should develop a comprehensive medical device postmarket surveillance strategy to collect, analyze and act on

medical device postmarket performance information”

• UDI system incorporated into EHR

• National and international device registries

• Modernize adverse event reporting

• New methods for evidence generation, synthesis and appraisal

Why Use Clinical Registries? • Clinical registries currently offer the only data sources

that include: • Granular clinical data needed for risk-adjustment • Medical device identifying information needed to capture

specific exposure• Detailed and relevant clinical outcomes

• Where Registries Fail Today: • Limited scope – capture of only specific devices and

conditions• Limited longitudinal follow-up

International Registry Participation

• Global Registry Participation Makes Sense• Benefits U.S., Since Devices Come Here Last• Harmonized Data Elements and Definitions

So “We All Speak the Same Language”• Identify Issues on a Larger Scale• Identify Regional/National Differences in

Practice, Performance, Outcomes• Possible Role in U.S. Regulatory Process

MDEpiNet FDA initiative

Cornell/International Consortium of Cardiovascular Registries TVT initiative

(ICCR- ICTVR) grant: Germany, France, Canada, United Kingdom,

Netherlands, and Japan

THE FUTURE MODEL OF QUALITY MEASUREMENT AND POST MARKET

SURVEILLANCE IS HERE!

Defining TVT Registry Collaboration SuccessProfessional Society Goals:

– The TVT Registry should maintain the traditional goals of the professional societies:1) Patient Care 2) education, 3) research, 4) members’ interests.

– Are the professional societies governing boards still supportive of the TVT Registry? – Are other professional societies being included or do they feel excluded?

Governance Goals: – Does the present structure work? – Leaders communicating well? Steering Committee decisions made appropriately? – R & P and the Stakeholders Committees functioning well?

Cost/Benefit Goal: The TVT Registry must provide benefits by meeting all goals and at a cost that can be considered reasonable, and ideally with an overall cost reduction.

Scientific Integrity Goals: – Objective, bias-free, and scientifically based reports?– Is the TVT Registry in compliance of COI policies from the STS and ACC for members

representing these entities?

Regulatory GoalsNew infrastructure for PAS and IDE studies

• Replacement of “off-label” use without data collection and lack of pathway to expand label indications.

• Leveraging costs and maximizing “quantity” of patient data

Medical Device Surveillance Goal• All implanted devices should be monitored with periodic

assessments of expected device-related adverse events and identification of an unanticipated adverse events.

• Device Efficacy and Safety: Sharing of the responsibility by more than FDA and Industry. Public-Private Partnership- MDEpiNet

Medical Device Industry Goals:

Does the medical industry view the TVT Registry as an improvement versus the prior system?

What do they see as the benefits versus the losses/sacrifices?

Edwards Lifesciences

TBDAbbott

VascularSt. Jude Medical

Medtronic

Financial Goals Is the TVT Registry Financially Viable and Sustainable?

Are We Under or Overestimating Costs?Are Professional Societies Using TVTR as “Income stream” to

support their societies’ other missions?Is Industry Taking Advantage or Have We Created a More Cost-

Effective Infrastructure for all? Are Costs Being Shifted to Hospitals, TVTR or CMS for Expanded

Indications Studies?

TVT Registry Formula for Success:Working Collaboratively with FDA and CMS

• Realizing that we are all in the “Same Boat”• Avoidance of “Turf Wars” – STS & ACC “holding hands”

– ATS and SCAI collaboration• Promotion of true transparency and “blame free”

environment – working towards solutions• Communication, communication and communication

– Weekly scheduled steering committee calls– Extemporaneous leadership calls

• Documentation, documentation and documentation

Key Alignment of CMS, Pre-Market and Post-Market FDA and the TVT Registry

• Truthfully- a continuous work in evolution• Constant alignment of stakeholder’s aims and goals• Sensitivity and maintaining focus to hospital/clinician

burden of data collection and costs• Acknowledgement and sensitivity to Industry needs

– Issues of availability to patient level vs. aggregate data, timeliness, industry independent analytical capabilities, and their own regulatory needs

– Requirements for PMS, PAS and IDE studies• Patient’s needs and rights – informed consent and IRB

issues for both IDE and PAS studies

“The Good”

• New collaboration between many partners• Capability for robust post market surveillance• Expansion of the role of registries

“The Bad”

• Burdensome data collection for sites• Initial and annual expense for sites• Site agreements, contracts, informed consent• Communication between all stakeholders is a

constant challenge in “uncharted waters”!!

“To Be Determined”

• Different stakeholders have different goals– FDA- “safe and effective”

– CMS- “reasonable and necessary”

– Professional Societies- “appropriate use”, guidelines– Industry-post approval surveillance

Phase 1 Phase 2 Phase 3Post-

Approval

Phase 4

Pre-Market Post-Market

Post-Market Registries

Role for New Generationof Clinical Registries

The Potential Breadth of TVT Registry