1. 1 Medical Device Registries: Multiple Applications Thomas P. Gross, MD, MPH Director Division of Postmarket Surveillance Office of Surveillance & Biometrics Center for Devices & Radiological Health AHRQ Annual Conference Registries for Evaluating Patient Outcomes Bethesda, Md. September 9, 2008

2. 2 Registry as a Vehicle: Regulatory Applications Registry as a Vehicle: Regulatory Applications Pre- & Postmarket Safety &/or Effectiveness Discretionary & Mandatory Surveillance & Observational Study Descriptive & Analytic Pre- & Postmarket Safety &/or Effectiveness Discretionary & Mandatory Surveillance & Observational Study Descriptive & Analytic

3. 3 Registries: Premarket Perspective Potential Applications  Provide data to support development & design of clinical trials  Provide historical comparator data (if rigorous)  Enhance safety assessments via broader analysis of adverse events  Provide access to product (outside of IDE trial)  Expedite approval of device modifications or labeling

4. 4 Registries: Premarket Perspective Safety Assessment Registries: Premarket Perspective Safety Assessment Adhesion Barrier Device Registry  Voluntary, European experience, 4K patients  Adjunct to U.S. pivotal, randomized trial  Assess safety profile  Self-reported events, “reassuring” profile

5. 5 Registries: Premarket Perspective Product Access Registries: Premarket Perspective Product Access PFO Occluder Device Registry  Withdrawal of Humanitarian Device Exemption status  Submission of Premarket Approval Applications required (supported by clinical trials)  Access to device for those outside of clinical trials  Voluntary, U.S., 2K patients

6. 6 Registries: Premarket Perspective Device/Labeling Changes Registries: Premarket Perspective Device/Labeling Changes Intra-ocular Lens Registry  Assess performance of IOLs in adults < 60 years  Established by American Academy of Ophthalmology  Post-IOL acuity & adverse events on 7K eyes  Indications changed allowing for younger age use

7. 7 Registries: Postmarket Perspective Potential Applications  Provide surveillance for “real-world” events  Assess generalizability of new technologies  Expedite time to market with reliable postmarket data  Provide vehicle for Post-approval Studies (PAS)  Promote evidence development for CMS’ national coverage decisions (NCDs)

8. 8 INTERMACS: Enhanced Surveillance FDA Reports INTERMACS Complete information No Yes Validated data No Yes Adjudicated data No Yes Standard definitions No Yes Representative No We hope so Under-reported Yes We hope not Denominator data No Yes

9. 9 INTERMACS: Post-approval Studies  Provides the necessary infrastructure  Patient consent, IRB sign-off, data acquisition & quality  Is cost efficient & allows for enhanced oversight  Accommodates different study designs  Temporary total artificial heart: single-arm registry; 30-day & 1 year survival, time on device, transplant rates, adverse events & product problems  Left ventricular assist device: cohort design (recipients of designated device vs. concurrent recipients of other LVADs); similar outcome measures & including quality of life

10. 10 Registries: Postmarket Perspective Early “Real-World” Experience & PAS Registries: Postmarket Perspective Early “Real-World” Experience & PAS Drug-eluting Coronary Stent Registry  Assess “real-world” experience  Multiple sites (~50), 2K patients  Sites vary by private/academic, implanting volume, geographic distribution  Outcomes of interest: MACE, unanticipated events  Descriptive findings  Periodic follow-up at 1, 6, 12 months

11. 11 Registries: Postmarket Perspective FDA PAS & CMS NCD Carotid Stent Registry  Carotid Stents: Initial  Vehicle for post-approval study  Assess “real-world” experience & training (3 levels)  Multiple sites, 1K patients, 30-day follow-up  Adjudicated neurological events  Carotid Stents: Extension  Expand under CMS coverage  Explore risk factors associated with stenting  Multiple sites, 10K patients, 30-day follow-up

12. 12 Registries: Postmarket Perspective Discretionary Study Hemostasis Device Registry  Collaborative effort with American College of Cardiology (use of National Cardiovascular Data Registry)  ~60 sites, 14K patients  Assess gender differences & device-specific risk of hemorrhagic complications

13. 13 Registries: From a Disease Perspective  Toxic Anterior Segment Syndrome (TASS)  Non-infectious inflammation post-surgery (mostly cataract removal)  Results in blurred vision to glaucoma or corneal transplant  Outbreaks periodically reported  Device relatedness is an issue  viscoelastics?  surgical instruments?  Registry maintained at University of Utah & cases also accrued via ASCRS website  Augment TASS registry with spontaneous reports & assess utility for identifying suspect causative agents

14. 14 FDA Registry Initiatives  Expand existing registries  National ICD registry (ACC NCDR & HRS): add lead safety fields (lead revision, extraction, abandonment & reasons for failure)  Conduct linkage studies with Medicare data  Society of Thoracic Surgeons National Cardiac Database: study long-term morbidity & mortality of transmyocardial revascularization  ACC NCDR: study long-term cardiac morbidity & mortality of drug-eluting coronary stents

15. 15 FDA Registry Initiatives  Compare registry performance  Medicare claims vs. prospectively collected registry data from the Vascular Disease Study Group of Northern New England  Morbidity & mortality associated with endovascular vs. open surgical repair of abdominal aortic aneurysm  Nest investigational study within registry  Uses PAS to expand indications  Rigorous investigational study design

16. 16 FDA Registry Initiatives Sentinel Initiative*: an effort to develop a national, integrated infrastructure of electronic healthcare data systems for medical product safety surveillance  Identify & characterize existing U.S. orthopedic implant registries. Explore potential for establishing distributed system. * http://www.fda.gov/oc/initiatives/advance/sentinel

17. 17 Thanks for Your Attention! For further information: thomas.gross@fda.hhs.gov