Share 35 Liver Policy: Analysis at 1 Year OPTN Liver and Intestinal Organ Transplantation Committee Forum September 16, 2014
Background On June 18, 2013, the OPTN implemented a number of changes to adult donor liver allocation: Extend regional sharing of livers to MELD/PELD 15+ candidates on a national basis ( Share 15 ) Regional sharing of livers to MELD/PELD 35+ candidates ( Share 35 ) National sharing of livers and intestines to liver-intestine candidates Liver and Intestinal Organ Transplantation Committee charged with monitoring the impact of allocation changes
Data Data provided for 2 eras: June 18, 2012 June 17, 2013 (Pre-Era) June 18, 2013 June 17, 2014 (Post-Era) OPTN data as of August 22, 2014 Types of data National and some regional/dsa data focused on: Transplants by MELD/PELD, CIT, distance Post-transplant outcomes Waiting list mortality DSA imports/exports
Methods Counts of waiting list deaths include: OPTN member reported removals for death OPTN member reported removals for too sick SSADMF deaths (pre-removal and within 30 days of removal within the period) Overall death rate presented as deaths per patient-year Intent-to-treat analysis for MELD/PELD 35+ waiting list outcomes Time to transplant, death, other removal from first entry into MELD/PELD 35+ category Analysis accounts for competing risks Post-transplant patient survival estimated using Kaplan-Meier
Transplants Share Type Status/Score Age Import/Export
Deceased Donor Liver Transplants by Era and Region 1050 1156 1078 957 901 Overall: 6029 Pre, 6357 Post # of Transplants 850 650 450 250 223 222 757 693 579 520 188 159 525 492 467 480 296 316 538 512 655 672 50 1 2 3 4 5 6 7 8 9 10 11 Region Pre-Era Post-Era
Deceased Donor Liver Transplants by Era and Status/Allocation Score % of Transplants 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% N=6029 N=6357 6.3% 6.1% 18.7% 73.1% Pre-Era 12.6% MELD/PELD Exceptions 47.5% MELD/PELD exceptions < 15 15-34 35+ Status 1 26.3% 66.1% Post-Era 10.1% MELD/PELD Exceptions 51.6% MELD/PELD exceptions Status or MELD/PELD Score
Deceased Donor Liver Transplants by Era and Region Median Allocation Score At Transplant (Status 1s Excluded) Median Match MELD/PELD Score at Transplant 36 34 32 30 28 26 24 22 20 31 30 29 29 25 24 30 29 33 35 28 27 31 30 25 25 US Overall Pre-Era: 27 Post-Era: 28 31 30 22 25 25 1 2 3 4 5 6 7 8 9 10 11 Region 23 Pre-Era Post-Era
Median Allocation MELD/PELD at Transplant, by DSA within Region and Era Pre-Era Post-Era 40 Variance across all DSAs = 14.3 Variance across all DSAs = 17.6 40 Median Match MELD @ Transplant 35 30 25 20 35 30 25 20 15 1 2 3 4 5 6 7 8 9 10 11 Region 15 1 2 3 4 5 6 7 8 9 10 11 Region
Deceased Donor Liver Transplants by Era and Share Type % Transplants 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% N=6029 N=6357 4.9% 5.0% 20.4% 31.8% 74.7% 63.1% Pre-Era Post-Era Local Regional National
Regional Shares Pre-Era and Post-Era 600 500 487 # Transplants 400 300 200 100 0 385 310 226 202 184 195 173 160 149 124 129 114 104100 76 40 25 36 10 12 11 1 2 3 4 5 6 7 8 9 10 11 Region Pre-Era Post-Era
Multi-Organ Transplants Liver-Intestine: 34 in Pre-Era, 75 in Post-Era 0.6% of Pre-Era, 1.2% of Post-Era Transplants 22 National Shares in Pre-Era vs. 53 in Post-Era Liver-Kidney: 504 (8.4%) in Pre, 535 (8.4%) in Post 90% local, 9% Regional in Pre-Era 67% local, 32% Regional in Post-Era
Organ Travel Distance, Cold Ischemia Time, Donor Risk Index
Organ Travel Distance, Cold Ischemia Time, and Donor Risk Index Median Distance organs traveled (miles) Pre Post Overall: 59 85 Local: 22 23 Regional: 231 236 National: 687 660 Median Cold Ischemia Time (CIT) (hours) Overall: 6.1 6.1 Local: 5.9 5.8 Regional: 6.7 6.7 National: 8.1 7.7 Median Donor Risk Index (DRI) Overall: 1.4 1.4 Local: 1.3 1.3 Regional : 1.5 1.4 National: 1.6 1.7
Increase in Organ Travel Distance for Regions 4, 5, and 7 Distance in Nautical Miles 0 200 400 600 800 + 60 + 115 + 55 Pre Post Pre Post Pre Post 4 5 7
Median Distance Livers Traveled, by DSA within Region and Era Pre-Era Post-Era # Miles 450 400 350 300 250 200 150 100 50 Variance across all DSAs = 2723.6 Variance across all DSAs = 6009.3 450 400 350 300 250 200 150 100 50 0 1 2 3 4 5 6 7 8 9 10 11 Region 0 1 2 3 4 5 6 7 8 9 10 11 Region
Median CIT, by DSA within Region and Era Pre-Era Post-Era Median CIT @ Transplant 10 9 8 7 6 5 4 3 Variance across all DSAs = 1.22 Variance across all DSAs = 1.15 10 9 8 7 6 5 4 3 2 1 2 3 4 5 6 7 8 9 10 11 Region 2 1 2 3 4 5 6 7 8 9 10 11 Region
Transplant Metrics for Recipients with Match MELD/PELD at Transplant of 35+ Factor Pre-Era Post-Era Distance 51 166 CIT 6.3 6.6 DRI 1.3 1.3 Length of Stay 16 15 MELD/PELD (Lab) 37 37 Median values reported
Livers Not Used
Livers Not Used Recovered for Transplant but Not Transplanted: 669 in Pre-Era (10.3 % of recovered) 653 in Post-Era (9.5% of recovered) Livers Not Recovered: 1149 in Pre-Era (14.1% of all donors) 1099 in Post-Era (13.0 % of all donors)
Livers Recovered for Transplant But Not Transplanted, by Era and Region # of Discards 200 180 160 140 120 100 80 60 40 20 0 29 19 183 170 57 50 38 61 108 98 37 26 43 34 US Total Pre-Era: 669 Post-Era: 653 46 38 16 14 56 49 1 2 3 4 5 6 7 8 9 10 11 Region 81 69 Pre-Era Post-Era
Transplant Outcomes
Six-Month Patient Survival Deceased Donor Liver Transplants Performed 120 Days Pre- and Post-Share 35 100 98 96 94 % Survival 92 90 88 86 84 82 Pre-Era: All Post Era: All Pre Era: 35+ Post Era: 35+ 80 1 2 3 4 5 6 Months Post-Transplant
Post-Transplant Mortality Rates Massie et al., AJT (in revision)
Waiting List Dynamics
Liver Waiting List Additions, Pre-Era and Post-Era, By Status/Allocation Score Status 1 < 15 15-34 35+ Inactive Total N % N % N % N % N % N Pre- Era 461 3.9 5,080 43.4 5289 45.1 730 6.2 155 1.3 11,715 Post- Era 421 3.5 5,275 43.4 5485 45.1 814 6.7 160 1.3 12,155 Net -40 +195 +196 +84 +5 +440
Liver Candidates With MELD/PELD Allocation Scores of 35+ at Month s End 150 140 141 Number of Candidates 130 120 110 100 90 90 80 Apr-12 Jul-12 Oct-12 Jan-13 May-13 Aug-13 Nov-13 Mar-14 Jun-14 Sep-14
Candidates on the Liver Waiting List at Month End, By Status/Allocation Score 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Inactive MP < 15 MP 15-34 MP 35+ Status 1
Waiting List Death Rates
Overall Liver Waiting List Death Rates: Deaths/Too Sick Per 100 Patient-Years Deaths/100 PY 20 18 16 14 12 10 8 6 4 2 0 Pre-Era Post-Era 18.8 18.9 18.5 18.5 (2967) (2931) No significant differences (Numbers of Deaths) 8.9 8.7 (44) (43) (3011) (2974) Adults Pediatrics Overall
Relative Risk of Waiting List Mortality, Post-Era vs. Pre-Era, By Ethnicity 1.6 1.4 1.2 Crude RR 1 0.8 0.6 0.4 0.2 0 White Black Hispanic Asian Other
Relative Risk of Waiting List Mortality, Post-Era vs. Pre-Era, By Region 1.8 1.6 1.4 1.2 Crude RR 1 0.8 0.6 0.4 0.2 0 1 2 3 4 5 6 7 8 9 10 11 Region
Relative Risk of Waiting List Mortality, Post-Era vs. Pre-Era Crude RR 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 15-19 20-25 26-30 31-34 Lab MELD Category
MELD/PELD 35+ Waiting List Outcomes: Competing Risks Analysis 1 N = 1720 N = 1998 Death Transplant Other Death Transplant Other 1 0.9 0.8 Transplant 0.58 0.9 0.8 Transplant* 0.66 Prob. of Outcome 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Death 0.32 Prob. of Outcome 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Death* 0.24 0 0 15 30 45 60 75 90 Days Since Entry: Pre-Era 0 0 15 30 45 60 75 90 Days Since Entry: Post-Era *Transplant rate, Death Rate Significantly Different, p< 0.05
Imports/Exports
Net Flow of Livers, Pre-Era vs Post-Era, by DSA MSD=184.4 Net Importers, Pre Net Exporters, Post 100 80 60 40 Net Exporters Pre and Post Net Flow, Post 20 0-100 -80-60 -40-20 -20 0 20 40 60 80 100 Net Importers, Pre and Post -40-60 -80-100 Net Flow, Pre Net Exporters Pre, Net Importers Post Pre: 06/18/2012 6/17/2013 Post: 6/18/2013 06/17/2014
Net Flow of Livers, Pre-Era vs Post-Era, by DSA MSD=187.4 Net Importers, Pre Net Exporters, Post 100 80 60 40 Net Exporters Pre and Post Net Flow, Post 20 0-100 -80-60 -40-20 -20 0 20 40 60 80 100 Net Importers, Pre and Post -40-60 -80-100 Net Flow of Livers, Pre Net Exporters Pre, Net Importers Post Pre: 06/18/2010 6/17/2011 Post: 6/18/2011 06/17/2012
Summary: Post Share 35 Era Data Increased number/percent of MELD/35+ transplants Increased regional sharing No impact to overall waiting list mortality No impacts to waiting list mortality by age, ethnicity MELD/PELD 35+ waiting list candidates Increased transplant rate Decreased mortality rate Post-transplant survival (preliminary) No overall change No change to outcomes for MELD/PELD 35+ recipients No impact to overall liver discard rate Overall import/export dynamics similar to previous era
Extras
Reminder: Share 15/35/LI-IN Algorithm 1. Combined local and regional status 1A candidates 2. Combined local and regional status 1B candidates 3. Local and regional candidates with M/P Scores >=35 by descending M/P score, local candidates ranked above regional candidates at each score 4. Local candidates with MELD/PELD scores 29-34 5. National Liver-Intestine Candidates 6. Local candidates with MELD/PELD scores 15-28 7. Regional candidates with MELD/PELD scores 15-34
Algorithm (cont.) 8. National Status 1A candidates 9. National Status 1B candidates 10. National Candidates with MELD/PELD scores >=15 11. Local candidates with MELD/PELD scores < 15 12. Regional candidates with MELD/PELD scores < 15
Deceased Donor Liver Transplants by Era, Age, and Status/Allocation Score % of Transplants 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% < 15 15-34 35+ Status 1 18.8% 27.2% 39.8% 38.0% 17.4% 16.5% 76.4% 63.8% 34.2% 38.2% 8.7% 7.3% Adult, Pre (N=5557) Adult, Post (n=5878) Pediatric, Pre (n=472) Pediatric, Post (n=479)
Deceased Donor Liver Transplants with MELD/PELD 35+, by Month 180 163 160 140 # Transplants 120 100 80 60 73 40 20 0 Jun-12 Sep-12 Dec-12 Apr-13 Jul-13 Oct-13 Jan-14 May-14 *June 2012/2014 are only partial months in the cohort, so were omitted
Transplant Metrics for Regionally Shared Livers Factor Pre-Era Post-Era DRI 1.5 1.4 CIT 6.7 6.7 Distance 231 236 LOS 11 12 M/P (Lab) 23 31 M/P (Match) 27 36
Liver Waiting List Additions by Month and MELD/PELD Score at Listing, July 2012-May 2014 90 80 70 Pre-Era Post-Era # of Additions 60 50 40 30 20 10 0 Month Status 1 35+ Inactive
Deceased Donor Liver-Intestine Transplants by Month 12 10 11 9 # Transplants 8 6 4 2 0 0 Jun-12 Oct-12 Jan-13 Apr-13 Aug-13 Nov-13 Feb-14 May-14 *June 2012/2014 are only partial months in the cohort, so were omitted
Liver Waiting List Additions by Month and MELD/PELD Score at Listing, July 2012-May 2014 600 500 Pre-Era Post-Era # of Additions 400 300 200 100 0 Month < 15 15-34
Liver Candidates Waiting for an Intestine at Month s End 120 111 100 88 Number of Candidates 80 60 40 20 0 Jun-12 Sep-12 Dec-12 Apr-13 Jul-13 Oct-13 Jan-14 May-14