1. Leveraging Operational Cardiovascular Registries: An ACC View Plenary Session: Novel Infrastructure for Clinical Trials & Innovation CSRC Transradial Thinktank Meeting FDA White Oak, Silver Spring July 29, 2013 Ralph Brindis, MD, MPH, MACC Senior Medical Officer, External Affairs, NCDR Clinical Professor of Medicine, UCSF Past President, American College of Cardiology

2. Background Overview of Issue Under Discussion Harnessing the potential power of national registries to be a seamless infrastructure for RCTs. –Leveraging 2500 hospitals and >1000 office based physicians in the NCDR –Casting a fishing rod into the Mississippi River of NCDR patient data streams Rapid RCT study recruitment Marked reduction in RCT costs Comparative Effectiveness Research and more

3. What Works Well Today!

4. 19982004200520062007200820102012 PVI 2500 hospitals > 2000 cardiologists 16 million clinical records 2500 hospitals > 2000 cardiologists 16 million clinical records

5. Science and Quality Education Advocacy Chapters

6. Data Quality

7. NCDR’s Data Quality Program 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 –Upto 650 records are audited annually. 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

8. ACC/Duke Partnership: Develop a National Cardiovascular Research Infrastructure (NCRI)

9. NCRI’s Infrastructure Opens Doors

10. Outcomes to CER to RCTs to Post Market to IDE

11. Major Advances of CV Registries as Novel Infrastructure for Clinical Trials & Innovation Efficiency –Due to vast data banks, data quality structures RCTs more efficient than ever imagined Decreased Cost –Both quicker and less expensive

12. Prospective, Observational Study: DAPT Among AMI-PCI Patients 1 Months 3 612 15 Index AMI Hospitalization Discharge FOLLOW-UP – Validated events, medications, costs ClopidogrelorPrasugrelor(Ticagrelor) Objectives: to evaluate long-term effectiveness and safety long-term effectiveness and safety adoption of novel antiplatelet meds adoption of novel antiplatelet meds short- and long-term Rx patterns short- and long-term Rx patterns antiplatelet medication switching antiplatelet medication switching patient adherence patient adherence economic cost implications economic cost implications www.translate-acs.org

13. SAFE-PCI for Women Study Pilot study for the National Cardiovascular Research Infrastructure (NCRI) grant S tudy of A ccess Site F or E nhancement of P ercutaneous C oronary I ntervention for Women

14. www.cvrn.org

15. CVRN Longitudinal Study of ICDs Circ Cardiovasc Qual Outcomes. 2012;5:e78-85.

16. CVRN ICD Study Aims Rates and determinants of adverse outcomes over 3 years Rates of appropriate and inappropriate shock in cohort and subgroups CER of single vs. dual chamber ICD

17. UDI system incorporated into EHR National & international device registriesNational & international device registries Modernize adverse event reporting New methods for evidence generation, synthesis and appraisalNew methods for evidence generation, synthesis and appraisal

18. TVT Collaborative Partnerships Clinical Registry Program Quality/Outcomes Research Device Surveillance Post-Approval Studies IDE Studies Network for RCTs Clinical Registry Program Quality/Outcomes Research Device Surveillance Post-Approval Studies IDE Studies Network for RCTs

19. What is Missing….. Does not Work Well Today “Opportunities for improvement”: –Facilitating smoothing the interface between registries, FDA, CMS and industry for streamlining RCT study designs, IRB requirements, data collection needs –Variable funding mechanisms and associated challenges

20. An Underused Opportunity for Using National Registries for RCTs and Innovation National Research Infrastructure

21. Phase 1Phase 2Phase 3 Post- Approval Phase 4 Safety is primary endpoint Highly selected population (must meet several selection criteria) Short duration Safety and efficacy are primary endpoints Highly selected population Short duration Safety and efficacy are primary endpoints Selected population Pivotal studies (randomized controlled trial, RCT) Longer duration FDA driven and negotiated Centers defined Generally a Phase 3 continuance Sample size pre-determined Study interval defined Sponsor driven Generally RCT or Claims based Direct product comparisons Costs collected Sample size pre-determined Study interval defined Pre-MarketPost-Market Product performance and safety data Effectiveness is the primary endpoint Hypothesis generating Large and usually undefined sample size Real world population Continuous duration Treatment not assigned Traditional Registries Role for New Generation of Clinical Registries Clinical registries provide a platform for phase 3 & 4 research

22. Highest Priority Short Term 1-3 Years Increased collaboration building on recent “Templates” using national registries: –FDA –CMS and private payers –Industry –Academia –Professional Societies Developing new templates

23. Sustainability is reliant on stakeholders commitment to using registries for needed purposes Sustainability is reliant on financial support: 1.Participant Subscription 2.NCD/CED Mandates 3.Payer/Health Plan Support 4.Industry Grants 5.Government/Non-profit Grants

24. Highest Priority Long Term 3-5 years National Consortium- advisory body for registry derived RCTs with all potential stakeholders –NHLBI, FDA, CMS, PCORI, patient groups, Industry, academia, etc. Transparent and full external RCT data access Stable funding and sustainable registry RCT model