1. REGISTRY APPROACHES in DEVICE SURVEILLANCE Fred H. Edwards, MD Director, STS Research Center Emeritus Professor, University of Florida

3. Origin of the Concept Origin of the Concept Goals Goals Organizational Structure Organizational Structure Registry Design Registry Design Participation Participation Studies Studies VisionVision

4. N Engl J Med.2012;366:873-875 Professional societies, the medical device industry, and the FDA should mobilize available resources now to improve postmarketing surveillance... Otherwise, we will no doubt be back here again.

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

6. Origin of the Concept Origin of the Concept Goals Goals Organizational Structure Organizational Structure Registry Design Registry Design Participation Participation Studies Studies VisionVision

7. GOALS Optimize Care for the TAVR Patient Optimize Care for the TAVR Patient

8. GOALS Clinical Data on all US TAVR ProceduresClinical Data on all US TAVR Procedures The Data Source for TAVR Device Studies The Data Source for TAVR Device Studies The Foundation for a Portfolio of DevicesThe Foundation for a Portfolio of Devices Controlled Rational DispersionControlled Rational Dispersion by providing

9. JAMA. 2012;308(10):962-963. doi:10.1001/2012.jama.10941JAMA. 2012;308(10):962-963. doi:10.1001/2012.jama.10941

10. HALLMARKS Patient Focus Patient Focus Cooperation Cooperation

11. Key Organizations TVT Registry FDA STS Edwards Lifesciences NHLBICMS DCRI ACC

12. Agenda Differences Different stakeholders have different goals Different stakeholders have different goals –FDA : “safe and effective” –CMS : “reasonable and necessary” –Professional Societies : “appropriate use”, guidelines –Industry : post approval surveillance, IDE studies

13. Origin of the Concept Origin of the Concept Goals Goals Organizational Structure Organizational Structure Registry Design Registry Design Participation Participation Studies Studies VisionVision

14. Organizational Structure Steering Committee Analysis & Warehousing Research & Publications Advisory Stakeholder Group

15. Steering Committee STS Members Michael Mack Fred Grover Fred Edwards Dave Shahian Ex Officio Members FDA - Danica Marinac-Dabic CMS - Jyme Schafer NHLBI - Frank Evans ACC Members David Holmes Ralph Brindis John Carroll Murat Tuzcu Staff Cynthia Shewan, Hilary Kirk Joan Michaels, Kathleen Hewitt, Barb Christensen Data Analytic Center DCRI

16. Origin of the Concept Origin of the Concept Goals Goals Organizational Structure Organizational Structure Registry Design Registry Design Participation Participation Studies Studies VisionVision

17. Key Elements of TVT Registry All TAVR procedures to be enteredAll TAVR procedures to be entered Short-term risk adjusted outcomesShort-term risk adjusted outcomes Long-term outcomesLong-term outcomes Quality of life metricsQuality of life metrics Appropriateness of use assessmentAppropriateness of use assessment Feedback for quality improvementFeedback for quality improvement Platform for device studiesPlatform for device studies

20. Data Collection Tool

21. Pop-ups provide guidance

22. Quality Check

23. (800) 257 – 4737 tvtregistry@tvtregistry.org REGISTRY SUPPORT

24. Data Quality Site training and supportSite training and support Internal data auditsInternal data audits External independent data auditsExternal independent data audits Adjudication of selected eventsAdjudication of selected events –Stroke –TIA –Aortic valve re-intervention

25. Short-term Outcomes

26. Long-term Outcomes 30-Day and 1-Year 30-Day and 1-Year –Mortality –Stroke –MI –Device performance –Quality of Life (KCCQ) CMS data link used for > 1 year outcomes

27. Steering Committee Analysis & Warehousing Research & Publications Advisory Stakeholder Group

28. Risk Model Predictive risk models tailored to this unique cohortPredictive risk models tailored to this unique cohort –Short-term risk adjusted outcomes –Long-term risk-adjusted outcomes Next-generation predictive risk modelsNext-generation predictive risk models –Predict benefit as well as risk QoL metricsQoL metrics Frailty metricsFrailty metrics Patient reported outcomesPatient reported outcomes Appropriate use assessmentAppropriate use assessment Coordination with other modelsCoordination with other models

29. Steering Committee Analysis & Warehousing Research & Publications Advisory Stakeholder Group

30. Stakeholder Advisory Group STS ACC SCAI AATS Industry Hospital System Consumer Groups Government (CMS, FDA, NIH) Public Member

31. Origin of the Concept Origin of the Concept Goals Goals Organizational Structure Organizational Structure Registry Design Registry Design Participation Participation Studies Studies VisionVision

32. November 2011

33. December 2011

34. May 2012

35. Participation 2012 2013

36. PATIENT RECORDS 2013 2012

37. TVT Registry Sites Enrolled

38. Origin of the Concept Origin of the Concept Goals Goals Organizational Structure Organizational Structure Registry Design Registry Design Participation Participation Studies Studies VisionVision

40. PAS Considerations Data Collection via TVTR Data Collection via TVTR Analytic Center Analytic Center Audit Audit Funding Funding

43. IDE STUDIES Alt Access in inoperable cohort Alt Access in inoperable cohort Alt Access in high-risk cohort Alt Access in high-risk cohort Valve-in-Valve Valve-in-Valve

44. IDE QUESTIONS Rationale for ACC/STS sponsorship Rationale for ACC/STS sponsorship Role of industry Role of industry Continued access protocol Continued access protocol Funding Funding

45. Origin of the Concept Origin of the Concept Goals Goals Organizational Structure Organizational Structure Registry Design Registry Design Participation Participation Studies Studies VisionVision

46. Milestones February 2011: Discussions between FDA, ACC and STSFebruary 2011: Discussions between FDA, ACC and STS July 2011: TVT Registry proposed at FDA Advisory PanelJuly 2011: TVT Registry proposed at FDA Advisory Panel November 2011: Edwards Sapien approved in U.S.November 2011: Edwards Sapien approved in U.S. November 2011: ACC and STS file NCD request from CMSNovember 2011: ACC and STS file NCD request from CMS Dec 2011: STS/ACC TVT Registry launchedDec 2011: STS/ACC TVT Registry launched May 2012: NCD issued by CMSMay 2012: NCD issued by CMS July 2012: TVTR web-based data entryJuly 2012: TVTR web-based data entry October 2012: 1,000 patients enrolledOctober 2012: 1,000 patients enrolled February 2013: First IDE study approvedFebruary 2013: First IDE study approved

47. A Portfolio of Device Registries Device A DeviceB Device C TVTRegistry

48. Phase 1 Phase 2 Phase 3 Post-Approval Phase 4 Pre-MarketPost-Market Post-MarketRegistries TVTR

49. Phase 1 Phase 2 Phase 3 Post-Approval Phase 4 Pre-MarketPost-Market Post-Market TVTR

55. Challenges Compliance / ParticipationCompliance / Participation Burden of Data CollectionBurden of Data Collection Auditing / Data QualityAuditing / Data Quality Research AccessResearch Access International HarmonizationInternational Harmonization SustainabilitySustainability

56. A Portfolio of Disease Registries Aortic Mitral Coronary CVDiseaseRegistry