Ralph Brindis, MD, MPH, MACC, FSCAI, FAHA Senior Medical Officer, ACC-NCDR October 15, 2014

1. Predictable And SuStainable Implementation Of National Registries For CV DevicesPlenary Session: Infrastucture Transformation & the Innovation EcosystemWhat we can and need to implement in the USA: An Academic View: Ralph Brindis, MD, MPH, MACC, FSCAI, FAHA Senior Medical Officer, ACC-NCDR October 15, 2014

2. The 2014 CV Specialist:Safety, Efficacy, Utility and Durability of CV Devices Sir Luke Fildes, 1887, The Tate Museum, London

3. Key Issues to Consider

4. Barriers for New Medical Devices at the Bedside • Barriers could be reduced through theimplementation of national registries that support prospective device trials while tracking utilizationthrough the product life cycle through: • The extension to IDE studies supporting device indication expansion & labeling • The development of predictable partnered models for seamless operational processes, cost and data access

5. 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 are lacking Today: • Limited scope – capture of only specific devices and conditions; limited breadth – Global reach and market penetration • Limited longitudinal follow-up

6. Key Issues to Consider • Infrastructure for: • Pre market IDE device submission • Post market surveillance • “Off indication” evaluation (CED) • Generic for different devices and device iterations • Develop comprehensive infrastructure for disease management • Comparative effectiveness analysis • Cost effectiveness research • Appropriateness of care analysis • Quality monitoring • Performance improvement opportunity • Observational and hypothesis-driven studies of “real world” practice

7. The Triumvirate in the Innovation Ecosystem Industry Sponsors Regulators – FDA- Payers Academia- Professional Societies

8. Key Issues • Different stakeholders have different goals • FDA- “safe and effective” • CMS- “reasonable and necessary” • Professional Societies- “appropriate use”, clinical practice guidelines • Industry-post approval studies, IDEs, required surveillance

9. Evidence Generation • PASSION Registry platform as a viable infrastructure for: CV Device Randomized Clinical Trials

10. Evidence Generation Infrastructure for PAS and IDE studies • Replacement of usual paradigm “off-label” use without ongoing data collection • Replacement of the lack of pathway to expand label indications. • Leveraging costs and maximizing “quantity” of patient data

11. Academic View of Regulatory Goals • Medical Device Surveillance • All implanted devices should be monitored with periodic if not real time assessments of expected device-related adverse events and identification of unanticipated adverse events. • Device Efficacy and Safety: Sharing of the responsibility by more than FDA and Industry. Public-Private Partnership- MDEpiNet

12. REMDES

13. Infrastructure Transformation • Data Quality • Data Access • Data Format • Data Content/Definitions • Data Security • Data Governance • Privacy • Analytical Methodologies

14. Potential Infrastructure Transformations • Insure longer period post-implementation f/u in Registries • Enhance Linkage with EMR • Linkage with CMS database for long term outcomes • Global harmonization of with OUS databases/studies based on VARC common definitions • Extension to pre-market use • Linkage with relevant databases for potential comparative effectiveness research • Example: TAVR TVT Registry with STS Surgical AVR • Software vendors

15. What Works Well Today!

16. Academia / Professional Society Roles • Provide focused expert input (with transparency regarding conflicts of interest) • Serve on DSMB / DMC / Adjudication committees • Contribute to guideline development, competency and accreditation standards, AUC, whitepapers, policy documents, writing groups and ACE • Act as a “trusted third party” for data • NCDR, post-market • Represent the patient - express opinions as to what might be acceptable safety risks.

17. Registries can be used for PAS, PMS, IDEs Pre-Market Post-Market Role for New Generation of Clinical Registries Phase 4 Post-Market Post- Approval Registries Phase 1 Phase 2 Phase 3

18. Traditional Clinical Research Studies

19. National Cardiovascular Research Infrastructure (NCRI) • Initiated in 2009 by DCRI and ACCF • Four goals to improve cardiovascular research

20. Registry PlatformClinical Research Studies • Economical • Reduces data entry burden • Real world population • Consecutive patients • Larger patient volumes • Can use central randomization mechanism • Ongoing data capture

21. Traditional Approach $$$ Longer Novel Approach $ Shorter

22. SAFE-PCI for Women

23. Current Post Market Studies

24. Health Information Technology Tipping Points for Efficient Registries • Paper based records being replaced with: • Electronic Health Records • Automatic Registry data field population • Device Telephonic Assessments • Computerized Databases • Standardized Data Definitions • Robust Professional Society National Registries – although siloed and episodic/procedure based • Development of Linked Databases for true longitudinal assessment

25. Maintaining and Improving the Quality of Data for CV Devices Registries Adjudication and Auditing Processes

26. Physician Adjudication • The TVT Registry has an adjudication worksheet that sites complete to capture more information about key events (For TAVR this includes TIA, stroke and re-intervention). • A physician team at Duke reviews each adjudicated event and may request more information from site. • The Duke clinical team has overturned 16% of the events they have adjudicated. • We are currently working on a process to report adjudicated results back to sites.

27. Formal Site Audits – Projected Timeline Release Final Audit Report to Committees Release Final Site Reports Pilot Audit Launch Release Draft Site Reports Final Audit Variables List Notify Selected Participants STS/ACC TVT workgroup formed Identified audit vendor Final Audit Report Generation Formal Audit Preparation Data Abstraction Appeal Phase July Aug. Sept. Oct. Nov. Dec. Jan. Feb. Mar. Apr. May June July Aug. Sept. 2015 2014

28. What is Missing….. Does not Work Well Today • Variable funding mechanisms & related challenges • Data Collection Burden for Sites • Major Cost: Humans extracting data from charts and finding and entering data elements not routinely gathered at site • Disconnect between EMR and Registries • Clarity on issues surrounding informed consent

29. Ethical Oversight of Research on Patient Care • Is it research? Uncertainty about whether the data collection and monitoring central to learning health care systems is actually research and if so, what kind of ethical oversight it should have. • What is needed? An analysis of the fit (or lack of) between the existing human subjects protection framework in use in the United States and the new kinds of data collection activities that are being, and increasingly will be, undertaken by learning health care systems. Mildred Z. Solomon and Ann C. Bonham, “Ethical Oversight of Research on Patient Care,” Ethical Oversight of Learning Health Care Systems, Hastings Center Report Special Report 43, no. 1 (2013): S2-S3.

30. The TVT Registry InfrastructureTypes of Studies and Level of Ethical Oversight • Observational studies using existing clinical data without the imposition of additional data collection requirements beyond what is necessary for clinical care (Oversight simplified). • Prospective observational studies, which may require some additional data collection but where clinical decisions remain with clinicians and patients (Oversight intermediate). • Interventional studies, where treatment condition is assigned (Oversight traditional). Joe V. Selby and Harlan M. Krumholz, “Ethical Oversight: Serving the Best Interests of Patients,” Ethical Oversight of Learning Health Care Systems, Hastings Center Report Special Report 43, no. 1 (2013): S34-S36.

31. Highest PriorityShort Term 1-3 Years • EMR integration • 100% data availability • Global Reach – Global Registry harmonization • Patient Consent • Governance • PAS studies and IDE labeling extensions – helps strike right balance between pre and post market evaluations

32. Sustainability is reliant on stakeholders commitment to using registries for needed purposes • Sustainability is reliant on financial support: • Participant Subscription • NCD/CED Mandates • Payer/Health Plan Support • Industry Grants • Government/Non-profit Grants

33. Highest Priority Long Term 3-5 years • National Consortium- advisory body for registry derived RCTs with all potential stakeholders • NHLBI, FDA, CMS, PCORI, AHRQ, patient groups, Industry, academia, etc. • Real-time analysis of data captured • Stable funding and sustainable registry and registry derived RCT model • Eliminate systematic redundancy • Clinical registries become the standard infrastructure for conducting pre and post market research.