1. Liver and Intestinal Organ Transplantation Committee Update on Liver Allocation and Distribution ACOT August 28, 2012 Kim M. Olthoff, MD, Chair David C. Mulligan, MD, Vice-Chair Ann Harper, UNOS/OPTN Liaison

2.  Allocation:  Allocate: “to apportion for a specific purpose or to particular persons or things” –merriam-webster.com  Current liver allocation is based upon the “sickest first” principle  Uses MELD allocation system  Allows for standard and non-standard exceptions  Alternative allocation models  Transplant benefit  Variations on MELD (ie MELD-Na) Liver allocation and distribution

3.  Distribution:  Distribution: “the position, arrangement, or frequency of occurrence (as of the members of a group) over an area or throughout a space”  –merriam-webster.com  Current liver distribution is based mostly upon “local first” principle  Broader sharing for high status and pediatrics  Alternative distribution models  Concentric circles  Population based Liver allocation and distribution

4.  2/27/2002: MELD /PELD Implemented  01/15/2005: “Share 15 Regional”  08/15/2005: Revised Status 1 and broader sharing for pediatric donor (age 0-17)  11/18/2010: Broader sharing of pediatric LIs and LI-INs from 0-10 yr old donors  12/15/2010: Regional sharing for Status 1s MELD/PELD historical timeline

5. 1.Combined OPO and Regional LI Status 1A 2.Combined OPO and Regional LI Status 1B 3.OPO LI MELD/PELD ≥ 15 4.Regional LI MELD/PELD ≥ 15 5.OPO LI MELD/PELD < 15 6.Regional LI MELD/PELD < 15 7.National LI Status 1A 8.National LI Status 1B 9.National LI MELD/PELD >=15 National LI MELD/PELD <15 Current Algorithm* *Does not include recently-approved liver-intestine policy

6. Despite improvements in liver allocation and distribution, waitlist mortality remains high for patients with higher MELD scores Significant disparity exists between OPOs and regions with regard to mean MELD at transplant and waitlist mortality How can we start to correct this problem? Problem Statement

7. Competing Risk Liver Waiting List Outcome Probabilities at 1-Year Candidates Added 2007-2010 *Status 1A/1B, and candidates with exceptions excluded N=10319 N=15810N=2363

8. Mean Match MELD @ Transplant* Deceased Donor Liver Transplants, 2010 by DSA within Region *Adults only, Exceptions. Some DSAs may overlap

9. Death Rates* @ 365 Days, Candidates Listed for a DD Liver Transplant 1/1/2008-12/31/09 By DSA within Region *Adults only, Calculated using Competing Risks, Exceptions, Initial MELD>=15, Candidates with an Initial Status of 1A/1B Excluded, DSAs with fewer than 10 events excluded

10. Proposal for Regional Sharing (February 2009) Request for Forum (June 2009) RFI and Survey (December 2009) Forum in Atlanta (April 2010) Board directed Committee “to develop recommendations to reduce geographic disparities in waitlist mortality” (June 2010) Concept Paper/Survey (December 2010) Policy Development History I

11. Presentations at AASLD, ASTS Winter Symposium, ATC (2010 and 2011) Public Comment (September - December 2011) Public Webinar (October 2011) Review of Comments (March 2012) Final Committee Vote (May 2012) Policy Development History II

12. Full Regional Sharing – strong opposition Concentric Circles – mixed support Extension of Share 15 Regional – strong support Tiered Regional Sharing – strong support for some level (29, 32, 35, other) Net Transplant Benefit – mixed support Options Considered

13.  Further SRTR modeling and analysis of death rates and post transplant outcomes in high MELD patients  Fall 2011- Proposal for public comment for regional sharing for high MELD patients and national sharing for MELD >15 prior to local/regional MELD <15  Addressed issues from public response with further analysis  MELD exceptions  Combined LK transplants  Proposal submitted to OPTN BOD June 2012  National Share 15  Regional Share 35 LIC Plan of action

14. Results: Waitlist Mortality – Intent to treat

17. MELD/PELD 35+ Candidates 2009 – 2011: By Region Candidates Reaching M/P 35+ All NoYes N%N%N Region 231387.632612.42639 1 2569587.084913.06544 3458691.14468.95032 4602291.45668.66588 5872585.1152714.910252 6106291.21038.81165 7372685.364414.74370 8301991.82688.23287 9395490.54159.54369 10306590.43269.63391 11363293.62486.43880 All4579988.9571811.151517 The percentage of all candidates listed who entered MP35+ ranged by region from 6.4% to 14.9%. Regions 2,5 and 7 had the largest numbers.

18. MELD/PELD 35+ Candidates 2009 –2011: Categories of Exceptions and Standard Cases MP35 CategoryN% HAT Exception1212.12 HCC Exception360.63 Liver-Intestine1412.47 Other Exception2754.83 Standard MELD/CRRT (HD 2x in week) 163128.52 Standard MELD/no CRRT351461.46 Total5718100.00 About 90% of the candidates in MP35+ were assigned standard MELD/PELD scores; less than 1% were HCC exceptions.

19. MELD/PELD 35+ Candidates 2009 –2011: Rates of Death* and Transplant By Kidney Listing/Dialysis *Includes candidates removed for too sick Being either on the KI WL or on dialysis was associated with higher death rates and lower transplant rates. Candidates on KI WL and on dialysis (N=430) had highest death rates at 90 days (39.1%) and lowest transplant rate (49.8%) (data not shown).

20. Hypothesis: Greater access to organs for sicker candidates will decrease their waiting list mortality, without a demonstrable increase in mortality for other candidates, due to the small number of candidates involved. Extension of Regional Share 15 => Share 15 National Share 35 Regional - Candidates with MELD/PELD scores of 35 and higher Policy Changes Proposed at Spring 2012 UNOS/OPTN BOD meeting

21. 1.Regional Status 1A 2.Regional Status 1B 3.Local MELD/PELD>=15 4.Regional MELD/PELD>=15 5.National Status 1A 6.National Status 1B 7.National MELD/PELD>=15 8.Local MELD/PELD<15 9.Regional MELD/PELD<15 10.National MELD/PELD<15 Share 15 National* * Adult Donors Only

22. 1. Regional Status 1A 2. Regional Status 1B 3. Local and Regional M/P >=35 4. Local M/P 15-34 5. Regional M/P 15-34 6. National Status 1A 7. National Status 1B 8. National M/P ≥ 15 9. Local M/P < 15 10. Regional M/P <15 11. National M/P < 15 Share 35R, Combined with Share 15N* 3.1 Local M/P 40 3.2 Regional 40 3.3 Local M/P 39 3.4 Regional M/P 39 3.5 Local M/P 38 3.6 Regional M/P 38 3.7 Local M/P 37 3.8 Regional M/P 37 3.9 Local M/P 36 3.10 Regional M/P 36 3.11 Local M/P 35 3.12 Regional M/P 35 * Adult Donors Only Passed by the UNOS/OPTN BOD June 2012 Implementation dates depend upon Chrysalis

23. Data to be reviewed every 6 months : Waiting list mortality by MELD score Post-transplant patient and graft survival Percent shared between OPOs Percent shared nationally Percent of MELD exceptions scores transplanted at high MELDs (35+) Plan for evaluation after implementation

24.  HCC patients get transplanted sooner than non-HCC patients  HCC patients have lower dropout rate than non-HCC patients across all regions  MELD, AFP and tumor size are predictors of dropout, but non-HCC still has higher drop-out Future allocation initiatives: HCC Exceptions

25. % Dropout within 12 Months: HCC and Non- HCC Candidates by Region

26.  Transplant rates and death rates vary markedly across regions, particularly at MELD scores > 15  HRSA has asked SRTR to pursue a redistricting project focused on reducing geographic disparities in liver distribution.  Liver committee determines principles of allocation (like reducing disparities, reducing waitlist death, offering to highest MELD candidates) and limits of transport times  Mathematical redistricting to design optimal regions based on these principles (Principles-Based Optimization)  Improvements to inference: transport time estimates to understand geographic limits of broader sharing; LSAM upgrades Future Distribution Initiatives: Re-imagining distribution units

27. Transplant rates across OPOs MELD 38-39: 18% to 86% Presented to OPTN BOD June 2012 by D. Segev and S. Gentry

28. Geography and Design Engineering  Principles-Based Optimization  Important to agree on the framework up front  Keep current OPOs intact?  How many regions?  How compact should the regions be? Contiguous?  What is the metric we are trying to optimize? (Decrease pre-transplant deaths?) (Reduce variance in MELD at transplant?)  How do we balance tradeoffs? Presented to OPTN BOD June 2012 by D. Segev and S. Gentry

29. Optimized redistricting  We regroup existing DSAs into novel regions using an integer programming model.  The model assigns each DSA to exactly one region, and includes constraints to ensure that the MELD level at which any region exhausts its supply of livers is similar across regions.  The model minimizes the sum of the squared distances between all the DSAs and the location of each region. Presented to OPTN BOD June 2012 by D. Segev and S. Gentry

30. Optimized Map 1 Presented to OPTN BOD June 2012 by D. Segev and S. Gentry

31. Optimized Map 2 Presented to OPTN BOD June 2012 by D. Segev and S. Gentry

32. Optimal maps reduce variance 4.3 4.6 2.5 2.5 Presented to OPTN BOD June 2012 by D. Segev and S. Gentry

33. Transport time and cold ischemia Presented to OPTN BOD June 2012 by D. Segev and S. Gentry Cold ischemic time only weakly correlated with distance traveled Distance is not a proxy for travel time

34. Goal: Minimize disparity Improve and maximize outcome Final rule: “Neither place of residence nor place of listing shall be a major determinant of access to a transplant.”