A Proposal for the IMACS ( I SHLT M echanically A ssisted C irculatory S upport) Registry James K. Kirklin April 20

1. A Proposal for the IMACS (ISHLT Mechanically Assisted Circulatory Support) Registry James K. Kirklin April 2011

2. Historical Development of ISHLT MCS Registries • 2002-2006 First MCS Registry. Ill-fated attempt to stage collection of tier 1 (demographics) and tier 2 (outcomes) data. • Registry discontinued in 2006. • 2005- consortium of ISHLT stakeholders in MCS therapy asked me and colleagues at UAB to lead response to NIH RFP for US database in MCS. • Result- INTERMACS, which earlier this year was awarded a 5 year renewal.

3. Historical Development of ISHLT MCS Registries • Subsequent efforts for an international MCS database focused on the Tx Registry model (collect incompletely validated data from all possible centers) • Efforts within ISHLT unsuccessful in a landscape of polarized views about US vs European location of database. No traction from EuroMacs or EuroTransplant in establishing a viable database. • 2007 – Revised ISHLT mission statement established MCS at equal priority level as Hrt and Lung Tx

4. Historical Development of ISHLT MCS Registries • Dec, 2010 – the Board reaffirmed its interest in establishing an MCS registry to further position ISHLT as the “home” for MCS clinical science and practice. • Further, emanating from the strategic planning process, the ISHLT Board pledged to reject “international politics” as an agenda for decision-making in favor of merit/quality-based decisions regarding initiatives of global ISHLT interest. Extending this principle to the MCS registry initiative, the board invited me to provide a formal proposal at this Board meeting.

5. MCS Registry Proposal • The novel concept I presented in December with agreement of the Board was the development of an ISHLT MCS Registry that focuses on collecting accurate, complete, and verifiable data from any non-US centers willing to commit to our data quality process. (This contrasts with the previous principle of getting any possible data, regardless of quality). This data would be combined with the INTERMACS data set to provide “scientific quality” analyses to seek truths in the global application of durable MCS , all under the ISHLT brand. • It is with the spirit of this historical evolution in the current ISHLT mission that I make the following proposal.

6. UMACS • Established in 2009 at the recommendation of NHLBI, UMACS is a not-for-profit group based at UAB for the sole purpose of contracting with national and international entities for the collection and/or analysis of data about outcomes in MCS therapy. • UMACS is NOT supported by the NHLBI and is not a part of INTERMACS. • This proposal is from UMACS. • UNOS would be subcontracted by UMACS (by prior agreement) only for data collection. • Center interactions, data management, and analyses would be performed by UMACS.

7. IMACS Registry UAB’s Experience with Registries (Why you should trust us) Int’l Years Inst Pts Congenital Heart Surgeons Society Registry (CHSS) Y 1984-1987 30 2,750 Cardiac Transplant Research Database (CTRD) N 1990-2010 46 10,000 Pediatric Heart Transplant Study (PHTS) Y 1993→ 44 4,000 ISHLT MCSD Registry (participated in the analysis) Y 2002-2005 655 Inter-agency Registry for Mechanically Assisted Circulatory N 2006→ 120 4,500 Assisted Circulatory Devices (INTERMACS) BeneMACS (Benelux countries with Thoratec) Y 2009→ 5 6 MedaMACS (End stage heart disease: medical treatment) N 2011→ 12 400

8. IMACS Registry Costs of Registries • Annual • Institutions Patients Cost ($) • ISHLT Tx 202,000 • Registry mechanics 46 (35 US) 170 • Analysis • ISHLT MCSD 60 655 75,000 • INTERMACS 120 1,500 2.7 million

9. IMACS Registry • Governance • ISHLT Board of Directors • IMACS Registry Director • UMACS • UNOS

10. IMACS Registry • Hospital Enrollment • During the last five years we have been contacted by a number of non-US hospitals desiring to either join INTERMACS or join an MCSD registry that had similar definitions and major data elements as INTERMACS. • We have also been contacted by “groups” of hospitals usually at the national level. • We would create, in collaboration with ISHLT, a proactive plan for hospital enrollment.

11. IMACS Registry • Inclusion Criteria • All approved MCSDs (country by country) • Exclusion Criteria • None

12. IMACS Registry • Adverse Events Major Events • Device malfunction Death • Infection episode Transplant • Bleeding episode Recovery • Neurological event Device exchange

13. IMACS Registry • Data Structure and Elements • Pre-implant Form • Implant Form • Discharge Form • Follow-up (every 6 months) Form • Adverse Events will be captured in the discharge form and the follow-up forms. • Note: Exchange of an LVAD or TAH will terminate the first record and will start a new record.

14. IMACS Registry • Data Entry: Two Mechanisms • Direct Entry: The hospital enters data into the ISHLT VAD Registry. • Indirect Entry: The hospital enters data into another database (a national database or consortium database: known as a collective). The data from the collective is imported into the ISHLT VAD Registry according to a precise technical protocol that will be created by UNOS. The collective would generate the “export file” that meets the UNOS specifications. This would be similar to the data transfers for the Tx registry.

15. IMACS Registry • Deliverables • A registry • Quarterly progress reports to ISHLT • Statistical Reports to ISHLT, hospitals, collectives, countries • Data Quality: create and implement a plan • Disciplined definitions of Outcome Events • Science/Research • Web Site (an addendum to the current ISHLT website)

16. IMACS Registry • Collective Enrollment • During the first year of registry • Identify and contact any existing MCSD registries (e.g. JMACS, BeneMACS) • Create technical document to specify the parameters for export files (collective to the IMACS Registry) • Implement the “download”

17. IMACS Registry Cost for the Registry* First Year Year 2 Year 3 UMACS $61.500 $50,000 $50,000 UNOS $133,500 $16,000 $16,000 Total $196,000 $66,000 $66,000 *excludes collective downloads

18. IMACS Registry Cost for the Registry and Statistical Report and Analyses* First Year Year 2 Year 3 UMACS $121.500 $94,000 $94,000 UNOS $133,500 $16,000 $16,000 Total $255,000 $110,000 $110,000 *excludes collective downloads

19. IMACS Registry Cost for the Registry If Statistical Report and Analyses Begin in Year 2* First Year Year 2 Year 3 UMACS $61,500 $110,000 $94,000 UNOS $133,500 $16,000 $16,000 Total $195,000 $126,000 $110,000 *excludes collective downloads

20. IMACS Registry • Guiding Principles • High Quality Database • Create and implement the registry • Match implants at a hospital with implants from industry • Require > 90% compliance with follow-up • Respond to queries about data inconsistencies or errors • Conduct training sessions • Provide Benefits to ISHLT • Own and direct an international high quality MCSD registry • Will complement the ISHLT transplant registry as ISHLT • emphasizes it’s role in MCSD research • Provides Statistical Reports and Research Analyses to • ISHLT Researchers • Provide Benefits to the hospital • Statistical summaries of their experience • Benchmark against the international experience • Participate in device research

21. IMACS Registry • RECOMMENDATIONS • Select proposal with data analyses and hospital reports beginning in year ($195,000 - 126,000 – 110,000) • Commit to a 3 year trial period to fully explore this concept , after which the Board reassesses all aspects before going further. • I would act as IMACS registry director for years I through 3 to make sure things are running well and that UMACS is maximally effective • An MCS committee would be formed to outline initial expectations and enrollment goals as well as opportunities for collective data downloads in MCS.

22. ISHLT MACS Registry Registries for Evaluating Patient Outcomes: A User’s Guide Second Edition 347 pages Publication: September 2010 Agency for Healthcare Research and Quality Advancing Excellence in Health Care www.ahrq.gov