Regulatory Science and Sustainable Implementation of National and International Medical Device Registries

1. 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, FSCAI Senior Medical Officer, ACC-NCDR March 24, 2014

2. Disclosure Statement of Financial Interest Senior Medical Officer, External Affairs ACC- NCDR Salaried Position

3. 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

4. All 14,210 Cases are Commercial TAVR288 Sites Enrolled in TVT Registry274 Sites Entering Data6 Sites > 200 Cases; 24 Sites > 100 Cases • Does Not Include All TAVR Cases in US • Over 10K Cases from Trials • Some Commercial TAVR Cases Before NCD, VA Cases

5. Sites Participating in TVT Registry (Currently TAVR) No TAVR sites in Alaska and Wyoming (currently patients served by Seattle and Colorado sites) • As of last week 288 TAVR sites fully enrolled. Additional sites being trained by Edwards and Medtronic will be added. • Approximately 43 sites have started commercial MitraClip use are already TAVR-TVT sites.

6. TVT Registry is a Major Collaborative Partnership

7. Governance

8. Steering Committee • ACC Members • Ralph Brindis • John Carroll • David Holmes • Murat Tuzcu Registry Operations Center NCDR Ex Officio Members FDA - DanicaMarinac-Dabic, John Laschinger CMS - Jyme Schafer NHLBI - Frank Evans Chair TVT R&P Subcommittee - John Rumsfeld DCRI – Eric Peterson STS Members • Fred Edwards • Fred Grover • Michael Mack • Dave Shahian • Data Analytics Center • DCRI • Staff • Cynthia Shewan, Tina Kourtis • Joan Michaels, Kathleen Hewitt, Barb Christensen

9. Research and Publications Committee 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 STS Members • Fred Edwards (Co-Chair) • Vinod Thourani • Jeffrey Jacobs • Todd Dewey • Data Analytics Center • DCRI, Eric Peterson • Staff • Cynthia Shewan • Mary Weideman • Joan Michaels • Kathleen Hewitt

10. STAKEHOLDER ADVISORY GROUP Robert Guyton, MD Chair STS Representative Eric Bates, MD Vice-Chair ACC Representative 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 Member Health System and Health Plans • Tom PriselacCedars-Sinai Hospital System Industry Representatives • Chuck Simonton, MD Abbott Vascular • Larry Wood Edwards Lifesciences • NusrathSultana, MD St. Jude Medical • Tom Armitage, MD Medtronic • Keith Dawkins, MD Boston Scientific Government Representatives • Bram Zuckerman, MD FDA liaison • John Laschinger, MD FDA liaison • DanicaMarinac-Dabic, MD FDA liaison • Marissa Miller, DVM NIH liaison • Marie Casey CMS liaison Society Staff Representatives Cynthia Shewan STS and Joan Michaels ACC

12. STS-ACC TVT RegistryThree Modules in 2.0 Release • Transcatheter Aortic Valve Replacement • Types • Native • Valve-in-Valve • Technologies • SapienTM • CoreValveTM • Transcatheter Mitral Valve Replacement • Types • Native • Valve-in-Valve • Valve-in-Ring • Technologies • SapienTM • Transcatheter Mitral Valve Repair • Types • Direct Leaflet • Technologies • MitraClipTM • Future Additions • Annular Reduction • 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

13. TVT Registry Mitral Module Workgroup Composition • ACC Members • John Carroll - Chair • Samir Kapadia Stakeholders STS Members • Fred Edwards • Patrick McCarthy • Craig Miller • 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 Data Analytic Center (DCRI) FDA - John Laschinger*** • STS, DCRI and ACC Staff • Cynthia Shewan and Donna McDonald – STS • Michael Booth and Paul Meehan - DCRI • Joan Michaels and Susan Fitzgerald – ACC *** Abbott Input Barathi Sethuraman Bhagya Gurusu Liz McDermott

14. Data Quality!!!! • Training and Clinical Support Team • Orientation webinars • Online FAQs • Live customer support • Email • Monthly webinars • Annual meeting with case reviews, etc. • Data Entry Integrity • Software value checks • Field level range parameters • Parent:Child fields • 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 • Data Accuracy • Up to 650 records are audited annually. • 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

15. 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

16. Adjudication Process: Additional Data and Physician Review at DCRI

17. “The FDA should develop a comprehensive medical device postmarket surveillance strategy to collect, analyze and act on medical device postmarket performance information”

18. UDI system incorporated into EHR • National and international device registries • Modernize adverse event reporting • New methods for evidence generation, synthesis and appraisal

20. 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

21. 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

22. THE FUTURE MODEL OF QUALITY MEASUREMENT AND POST MARKET SURVEILLANCE IS HERE! MDEpiNet FDA initiative Cornell/International Consortium of Cardiovascular Registries TVT initiative (ICCR- ICTVR) grant: Germany, France, Canada, United Kingdom, Netherlands, and Japan

25. Defining TVT Registry Collaboration Success Professional 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?

26. Regulatory Goals • New 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

27. 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? TBD Medtronic Abbott Vascular St. Jude Medical Edwards Lifesciences

28. 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?

29. 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

30. 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

31. “The Good” • New collaboration between many partners • Capability for robust post market surveillance • Expansion of the role of registries

32. “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”!!

33. “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

34. The Potential Breadth of TVT Registry Pre-Market Post-Market Role for New Generation of Clinical Registries Phase 4 Post-Market Post- Approval Registries Phase 1 Phase 2 Phase 3