Seventh Annual Meeting New Data, New Thoughts, New Directions April 5-6, 2013 5:30pm to 9:00pm Crowne Plaza National

1. Seventh Annual Meeting New Data, New Thoughts, New Directions April 5-6, 2013 5:30pm to 9:00pm Crowne Plaza National Airport Arlington, VA INTERMACS Annual Meeting, April 2013

2. INTERMACS Seventh Annual Meeting April 2013 • Financial Disclosure Disclosure:Current guidelines state that INTERMACS member make aware any affiliation or financial interest that may affect that associate’s participation. Each member has been requested to complete a disclosure statement. The names of the members that have indicted a relationship which could be perceived as a potential conflict of interest (e.g. ownership of stock, significant honoraria/consulting fees, or direct research support from a commercial organization) are listed below. Additionally, all presentation speakers have been asked to disclose any financial interest or affiliations and to indicate if a product they are discussing is not labeled for the used under discussion or is still investigational. INTERMACS Annual Meeting, April 2013

3. Session 1 Friday, April 5 5:30pm – 9:00pm INTERMACS Annual Meeting, April 2013

4. Welcome James Young INTERMACS Annual Meeting, April 2013

5. INTERMACS: Accomplishments & Challenges James Kirklin INTERMACS Annual Meeting, April 2013

6. Original Contract May 31, 2005 – May 30, 2010 Contract Extension May 31, 2010 – November 30, 2010 Latest Contract December 1, 2010 – November 30, 2015 INTERMACS Annual Meeting, April 2013

7. Article C.1. Statement of Work Original Contract and Deliverables May 31, 2005 – May 30, 2010 (Highlights) INTERMACS Annual Meeting, April 2013

8. Original Contract: May 2005 – May 2010 The Contractor shall Collect information pertaining to patients, care providers, hospitals, devices and provide customized data sets. Develop protocols to collect data to answer research questions. Establish a Steering Committee to include at least 1 representative from CMS, FDA, a study chair, DCC PI, members from representative participating hospitals and the NHLBI Project Officer. Develop drafts and the final protocol, establish standard procedures and forms and provide and distribute the forms. Submit the protocol and any amendments thereto, to the DSMB for review and the NHLBI for approval. INTERMACS Annual Meeting, April 2013

9. Original Contract: May 2005 – May 2010 Work with the SC to develop criteria for certification and approval of each participating hospital as a member of the Registry. Develop methods to expeditiously implement certification and to monitor hospital performance. Work with the SC to establish policies and procedures to ensure satisfactory performance by participating hospitals. Train staff of participating hospitals in Registry methods of data, blood and tissue collection such that eligible hospitals can be certified to participate in the Registry. Eliminate hospitals failing to meet or maintain performance standards and identify and certify replacement hospitals. Work with the SC to develop a manual of operations based on the Registry protocol for the participating hospitals and obtain NHLBI approval of the MOO. The MOO shall include plans for collecting patient data in compliance with patient privacy regulations and for proper cross referencing to the source documents. (Protect proprietary information while analysis of safety and outcomes is enabled); Include policies and procedures including standard definitions of adverse events and other key definitions of endpoint of interest. Include operating policies such as publications, conflict of interest and data sharing. INTERMACS Annual Meeting, April 2013

10. Original Contract: May 2005 – May 2010 Work with the SC to develop an informed consent document (with required elements) for use by each participating hospital. Ensure that consents contain NIH elements and IRB approvals are current. Serve as the repository for the clinical data collected This will require the following: Develop procedures to inform appropriate personnel at each participating hospital of the requirements for data collection; Monitor hospitals to ensure the data are forwarded to the DCC in a timely manner; Review all clinical data transmitted by the participating hospitals to ensure completeness and quality control prior to processing; Develop a procedure for analysis of a large number of clinical measures needed to characterize patients enrolled and their outcomes including functional status, adverse events, subsequent hospitalizations, quality of lie and survival; Maintain liaison with each participating hospital to assist in the resolution of operational problems involved in collecting and reporting data; Develop computer software necessary to process and store all clinical data electronically; INTERMACS Annual Meeting, April 2013

11. Original Contract: May 2005 – May 2010 Provide statistical analysis of the data and develop the necessary software for this analysis. Prepare and distribute monthly reports to include patient recruitment in various categories and the hospitals providing the data, status of follow-up data collection, data analysis, problems encountered, if any, with the quality of data received. Develop standard reports for CMS. Develop standard reports for FDA in accordance with FDA requirements. Every 3 months provide to the NHLBI a summary of data collected and received during that period on patients receiving MCSDs. - Part of Quarterly reports. Prepare and distribute to the participating hospitals brief semi-annual summaries of the progress of the Registry. Arrange meetings of the DSMB to be held at least twice a year, provide summaries of the data analysis and specific patient data sets as requested by NHLBI and DSMB Members. Prepare and distribute minutes of the meetings. Coordinate with the NHLBI and manage meetings and conference calls of the SC; prepare and distribute minutes of the meetings. INTERMACS Annual Meeting, April 2013

12. Original Contract: May 2005 – May 2010 Plan and conduct an annual conference for Registry and other interested investigators to present and review MCSD Registry data. Prepare interim limited access data sets, consistent with NHLBI policies. Provide interim data sets to NHLBI approved investigators. Provide a final consolidate copy of patient data in hard copy and computerized tape formats, along with the supporting documents. Transcribe into Registry forms and enter into the Registry data base, information on patients that received MCSDs as destination therapy for heart failure prior to the initiation of the MCSD Registry. Perform site visits with record audits to determine the accuracy of web-based data submitted and information contained in source documents. Work with participating hospitals to prepare for publication abstracts and manuscripts resulting from the Registry. INTERMACS Annual Meeting, April 2013

13. Goals of the Registry • Facilitate the refinement of patient selection to maximize outcomeswith current and new device options. • Identify predictors of good outcomes as well as risk factors for adverse events after device implantation. • Develop consensus “best practice” guidelines to improve clinical management by reducing short and long term complications of MCSD therapy. • Guideclinical application and evolution of next generation devices. • Utilize Registry information to guide improvements in technology, particularly as next generation devices evolve. INTERMACS Annual Meeting, April 2013

14. Contract Extension Deliverables May 31, 2010 – November 31, 2010 INTERMACS Annual Meeting, April 2013

15. Latest Contract and Deliverables December 1, 2010 – November 31, 2015 (Highlights) INTERMACS Annual Meeting, April 2013

16. Latest Contract: Dec 2010 - Nov 2015 1. Implementation of a collaboration plan that integrates Industry and other non- NHLBI groups for financial support • Data quality and completeness, data access, objectives, policies and procedures • External advisory board 2. Maintaining Registry/Data Coordinating Center • Continue data collection on current and new patients • Maintain above • Develop and maintain a computer system • Website (distribution of info) • Section 508 compliance • Develop software for future government use – • Submit information system security plan – • Revise protocol and informed consent to reflect INTERMACS as the recipient, verify required elements, re-consent all current patients • Maintain procedures to inform sites of requirements for data collection per protocol and Manual of Operations • Monitor hospitals to ensure data are forwarded to DCC in a timely manner- • Maintain data quality and reporting compliance by reviewing all clinical data transmitted by sites to ensure completeness and quality control. • Maintain liaison with sites to assist in resolution of problems collecting and reporting data. INTERMACS Annual Meeting, April 2013

17. Maintain and support existing OC and SC structure and function including NIH, CMS, FDA, PIs, Sites, Sub-committees. Schedule meetings, conference lines, meeting facilities, materials, bulletin area on password protected website, meeting minutes and reports. • Arrange conference calls for OSMB, provide summaries, prepare and distribute minutes • Maintain certification of new and existing sites, monitor hospital performance, develop and train new sites/staff and provide review program, institute remedial actions for hospitals failing to meet or maintain performance standards or eliminate sites unable to maintain standards in collaboration with the Hosp. Training and Standards Committee • Maintain and support regulatory requirements for patient privacy and good clinical practices, new site IRB submission and regulatory documents for existing sites. Assure consents have NIH required elements • Expand and augment collection of functional capacity, health status (qual. of life) and neurocognitive assessments • Provide statistical analyses to Federal partners and DAAP approved investigators • Prepare and distribute quarterly reports for sites including patient recruitment, status of follow-up, data compliance, etc. • Quarterly individualized industry data reports INTERMACS Annual Meeting, April 2013

18. Latest Contract: Dec 2010 - Nov 2015 11. Semi-annual progress reports of the registry 12. Plan and conduct annual conference 13. Prepare interim limited data sets consistent with NHLBI policies 14. Six months before end of contract, provide a final copy of de-identified data in hard copy and computerized disc formats along with support documents 15. Conduct site visits to 100% of sites. Perform record audits to determine accuracy of WBDE and conduct for-cause visits/audits as needed 16. Work with sites and investigators to prepare abstracts and manuscripts 17. Extend research collaborations beyond the current INTERMACS investigators 18. Develop and execute procedures to made data collection software and associated documentation transportable for future government or non- government use. 19. Conduct Pilot registry (MedaMACS) INTERMACS Annual Meeting, April 2013

19. COST SHARING REPORT Funding Support December 1, 2010 – March 29, 2013 INTERMACS Annual Meeting, April 2013

20. COST SHARING REPORTDecember 1, 2010 – March 29, 2013 INTERMACS Annual Meeting, April 2013

21. Workshop for the Executive Committee, FDA, and Industry INTERMACS Form Revisions • May 31, 2007 Minor revisions to web-based data entry (Protocol v2.2) • March 5, 2009 Significant form revision (e.g. bleeding form) (Protocol v2.3) • May 2, 2012 INTERMACS Re-Launch (Protocol v3.0) INTERMACS Annual Meeting, April 2013

22. Additional Initiatives • Quality Assurance Reports • Medical Device Reports • Medical Event Review INTERMACS Annual Meeting, April 2013

23. Seventh Annual Meeting, April 5-6, 2013 Publication Record Number of co-authors: 154 Number of abstracts: 48 Number of published papers: 18 Number of citations: 824 Google Scholar search results for the term INTERMACS: 1,330 INTERMACS Annual Meeting, April 2013

24. Publications June 2006 - March 2013 48 18 # of abstracts/publications (Thru March) INTERMACS Annual Meeting, April 2013 Year

25. Fifth Annual Meeting, April 12, 2011 • INTERMACS for Pre and Post Market Studies • From the beginning of INTERMACS, FDA has been an active partner and has been “at the table” during all discussions of adverse event definitions, quality of life assessment, neurological assessment, functional capacity measurements, follow-up schedule, audit process, medical event review, etc. • FDA has encouraged device manufacturers to review all aspects of INTERMACS as they plan their pre-market and post market studies. INTERMACS Annual Meeting, April 2013

26. Benefits of using INTERMACS for post market studies • FDA receptive to using INTERMACS registry in order to meet PMA conditions of approval post market studies • INTERMACS study protocol already approved by the Institutions IRB • Institution personnel involved in MCS therapy already trained and familiar with INTERMACS data entry requirements • Reduces the burden for study sites because they don’t have multiple study CRFs to complete to meet the PAS requirements • INTERMACS registry data can serve as a contemporaneous control group to evaluate new MCS performance in a commercial setting • Enrollment can begin immediately after MCS device manufacturer receives FDA approval for their PAS protocol • INTERMACS provides periodic data summaries to allow MCS manufacturer to quickly summarize and prepare PMA post approval periodic reports • INTERMACS can assist enrolling centers in meeting MDR User Facility reporting requirements • INTERMACS PAS data can be used to update labeling with real world experience • Use of INTERMACS registry is the least burdensome and most cost effective means to gather required PAS data to meet PMA condition of approval study requirements INTERMACS Annual Meeting, April 2013 4

27. Workshop for the Executive Committee, FDA, and Industry Pre- and Post Market Studies Using INTERMACS Summary Post Market Studies Thoratec, HMII BTT Post Market Study complete Nov 2011 Results confirm pivotal trial Thoratec, HMII DT Post Market Study will be complete 2013 Pre-Market Studies Berlin Heart, EXCOR Pre-Market FDA Approval 12/16/2011 (INTERMACS provided statistical support) Heartware, HVAD Pre-Market FDA Approval 11/20/2012 INTERMACS Annual Meeting, April 2013

28. The ‘MACS’ Family • INTERMACS • INTERMACS: Adults • pediMACS: Pediatric • CanaMACS: Adults + Pediatric • IMACS (ISHLT Initiative) • MEDAMACS (Medically treated patients) • JMACS • BENEMACS INTERMACS Annual Meeting, April 2013

29. Seventh Annual Meeting, April 5-6, 2013 PediMACS U-MACS INTERMACS INTERMACS Annual Meeting, April 2013 MedaMACS IMACS

30. Seventh Annual Meeting, April 5-6, 2013 • Partnerships • Federal Partners – FDA, CMS, NHLBI • Industry • Member Institutions/Centers INTERMACS Annual Meeting, April 2013

31. Panel Discussion: NIH Marissa Miller INTERMACS Annual Meeting, April 2013

32. A Dialogue on Current Budget Challenges and Their Impact on INTERMACS Marissa A. Miller, DVM, MPH Chief, Advanced Technologies and Surgery Branch National Heart, Lung, and Blood Institute Financial disclosures: None INTERMACS Annual Meeting April 5, 2013 INTERMACS Annual Meeting, April 2013

33. INTERMACS Annual Meeting, April 2013

34. Budget Control Act of 2011 INTERMACS Annual Meeting, April 2013 ***Gross Public Debt stood at $14.3 trillion ***Immediate $400 billion increase in debt ceiling, additional increases of $1.7 trillion ***Initial $900 billion cut in spending over ten years, largely from discretionary spending. Capped discretionary spending going forward ***Established the Joint Select Committee on Deficit Reduction, the “Super Committee” tasked with Identifying $1.2 to $1.5 trillion in additional cuts ***Failure to do so would lead to automatic cuts starting, 50% defense/50% non-defense ***Excluded Medicaid, Social Security, and Medicare Beneficiaries. Provider cuts limited to 2%

35. The Sequester INTERMACS Annual Meeting, April 2013 “[Congress] and the administration knew that this sequester would be destructive…. [T]he sequester wasn’t meant to be implemented…. “[N]o amount of planning or reports will turn the sequester into anything other than the devastating cut in defense and domestic investments that it was meant to be.” Jeffrey Zients, acting director, Office of Management and Budget, Politico, 7/10/12 Nonetheless, it is the law

36. The Sequester INTERMACS Annual Meeting, April 2013

37. Explicit Challenges Rock Talk Helping connect you with the NIH perspective NIH Operations Under the Sequester Posted on March 4, 2013 by Sally Rockey Dear NIH Signing Official, As you are likely aware, in accordance with the Budget Control Act of 2011, a series of spending cuts, called sequestration, will cancel approximately $85 billion in budgetary resources across the Federal government for the remainder of the Federal fiscal year.  As a partner with you in accomplishing the NIH mission, we are writing to provide you with information about what this reduction means for the funds provided to your organization. At this time, the Department of Health and Human Services and NIH are taking every step to mitigate the effects of these cuts, but based on our initial analysis, it is possible that your grants or cooperative agreement awards may be affected.  Examples of this impact could include: not issuing continuation awards, or negotiating a reduction in the scope of your awards to meet the constraints imposed by sequestration.  Additionally, plans for new grants or cooperative agreements may be re-scoped, delayed, or canceled depending on the nature of the work and the availability of resources. INTERMACS Annual Meeting, April 2013 http://nexus.od.nih.gov/all/2013/03/04/nih-operations-under-the-sequester/

38. Explicit Challenges Sequestration notice sent out to all NIH Contractors Monday March 04, 2013 To All NIH Contractors: …”it is possible that your contract(s) may be affected.  Examples of this impact could include:  not exercising an option on your contract(s); or negotiating lower prices or other terms via a bilateral modification to meet the constraints imposed by sequestration.  Additionally, plans for new contract(s) may be re-scoped, delayed, or canceled depending on the nature of the work and the availability of resources.” INTERMACS Annual Meeting, April 2013 Per Diane J. Frasier: Head of the Contracting Activity, NIH

39. The Elephant INTERMACS Annual Meeting, April 2013

40. Our Failing Business Models INTERMACS Annual Meeting, April 2013

41. The New Normal INTERMACS Annual Meeting, April 2013 • What to expect in times of reduced funding • Fewer dollars especially for Institute Initiated Programs (substantial cuts to contracts) • Necessity to be creative (large simple trials/EMR) • Critical assessment of how and what is funded • INTERMACS • Strengthening the Public Private Partnership • Improving Quality Systems • Streamlining Regulatory Activities • Leveraging Resources and Partnerships • Thinking Outside the Box

42. INTERMACS Annual Meeting, April 2013

43. Explicit Challenges The U.S. system for funding research was designed to function well in times of growth. It is failing now because the system as a whole is contracting. Much of today’s proposal pressure is caused by underfunded investigators who must compete for multiple grants to survive professionally. Such scientists have little time or incentive to be innovative. What is to be done? The funding agencies must admit that it is not humanly possible to predict, with high accuracy, which research projects ultimately will have the most impact. When there are too many of these, as at present, the agencies must find other ways to decide which to support. That will be hard. INTERMACS Annual Meeting, April 2013 Langer J. Science 2012; 388:171

44. Even More Explicit With 10 to 15% paylines at some institutes (or even less), the current situation makes grant evaluation nearly impossible and is putting truly excellent laboratories out of business. In the spirit of “never waste a good crisis,” a serious evaluation of many NIH extramural policies and programs is warranted. They include centers and other large collective funding efforts as well as expensive clinical and epidemiological research. INTERMACS Annual Meeting, April 2013 Rosbash M. Science 2011; 333:136

45. In Progress: Comparisons on Percentiles Cites/$M INTERMACS Annual Meeting, April 2013 Percentile Thanks to Simhan Danthi, Colin Wu, and Peibei Shi

46. Panel Discussion: FDA AnchalKaushiva INTERMACS Annual Meeting, April 2013

47. FDA Perspective on INTERMACS Anchal Kaushiva, M.S. Division of Cardiovascular Devices Office of Device Evaluation Food and Drug Administration INTERMACS Annual Meeting April 5-6, 2013 INTERMACS Annual Meeting, April 2013 47

48. Center for Devices (CDRH) ODE (Pre-market Device Evaluation) OSB (Surveillance and Biometrics) OC (Compliance/Inspections) Division of Post-market Surveillance (MDRs) Division of Epidemiology (Post-approval studies) FDA Center for Devices INTERMACS Annual Meeting, April 2013

49. INTERMACS Utility to FDA Has been used for post-approval studies Served as the concurrent control for a pre-market study Provides MDR reports on behalf of user facilities Has allowed for detection of adverse event signals Provides quarterly reports of the data collected INTERMACS Annual Meeting, April 2013

50. INTERMACS Accomplishments Adverse Event Definitions Creation of INTERMACS patient profiles Data collection has tracked: Evolution of MCSD technology Patient risk profiles Patient outcomes Expansion to PediMACS, MedaMACS, IMACS INTERMACS Annual Meeting, April 2013