1. Axel Rahmel Organ Donation and Transplantation in the European Union Challenges and opportunities of international cooperation in organ allocation Technical Assistance for Alignment in Organ Donation 1 st International Symposium Istanbul – May 29-31, 2014

2. European Organ Exchange Organizations (million pop.). 7.1 7.2 10 10.3 11 21 24.2 38.2 43.2 56.9 61.5 62.9 135 Baltransplant SwissTransplant OPT Portugal Czech Transplant Hellas NTO NTA Romenia Scandiatransplant Poltransplant ONT Spain CNT Italy ABM France UKTransplant Eurotransplant

3. Organ Procurement Organization Transplant- center National Competent Authorities Transplantat Law Organ donation Allocation Transplantation Distribution of tasks in organ transplantation

4. WHO GUIDING PRINCIPLES ON HUMAN CELL, TISSUE AND ORGAN TRANSPLANTATION Guiding Principle 9 Where donation rates do not meet clinical demand, allocation criteria should be defined at national or subregional level by a committee that includes experts in the relevant medical specialties, bioethics and public health…

5. WHO GUIDING PRINCIPLES ON HUMAN CELL, TISSUE AND ORGAN TRANSPLANTATION Guiding Principle 9 The allocation of organs, cells and tissues should be guided by clinical criteria and ethical norms, not financial or other considerations. Allocation rules, defined by appropriately constituted committees, should be equitable, externally justified, and transparent.

6. Aims of organ allocation Finding a suitable donor organ for all patients on the waiting list (including special patient groups) …in time Optimizing the match between donor and recipient to improve long term outcome of transplantation Preventing organ loss

7. Requirements for an organ allocation system Objectivity ■ Allocation is independent of subjective factors (procurement and allocation organization, transplant center) Reliability ■ With same donor information and same waiting list information an identical matchlist is generated Transparency and accountability ■ Every step in the allocation process is documented and can be explained Validity of allocation criteria ■ Ethically acceptable, medically based ET office ET AC

8. Requirements for an organ allocation system Objectivity ■ Allocation is independent of subjective factors (procurement and allocation organization, transplant center) Reliability ■ With same donor information and same waiting list information an identical matchlist is generated Transparency and accountability ■ Every step in the allocation process is documented and can be explained Validity of allocation criteria ■ Ethically acceptable, medically based ET office ET AC

9. The allocation center

10. Donor dataRecipient data Match

11. Matchlist  Allocation

12. Requirements for an organ allocation system Objectivity ■ Allocation is independent of subjective factors (procurement and allocation organization, transplant center) Reliability ■ With same donor information and same waiting list information an identical matchlist is generated Transparency and accountability ■ Every step in the allocation process is documented and can be explained Validity of allocation criteria ■ Ethically acceptable, medically based ET office ET AC

13. Allocation – The key steps Step 1 - Selection: Identifying those patients that are suitable at all for a specific organ among all patients on the waiting list. Step 2 - Ranking: Determining the allocation sequence among all suitable recipients.

14. Selection of suitable recipients Selection criteria Blood group Age (specific programs) Organ specific matching factors Size, weight, total lung capacity (TLC) Recipient and center profile Donor age Donor risk factors Virology (Hep B, C (maybe in the future HIV) History of malignancy Drug abuse Sepsis Meningitis

15. Selecting: recipient and center profile

16. Determination of the Matchlist Selection and Ranking A H J E I D F G C B Waiting list Day 1 Donor A 65 yrs, 50kg X X X X X X Matchlist 1 Pat. „C“ is number 2 on the matchlist

17. A H J E I D F C B Waiting list Day 2 K G D Determination of the Matchlist Selection and Ranking

18. A H J E I D F C B Waiting list Donor B 40 yrs, 75kg K X X Matchlist 2 Pat. „C“ is number 5 on the matchlist Determination of the Matchlist Selection and Ranking

19. Urgency Outcome Balancing urgency and outcome

20. Examples of the consequences of allocation trade-offs Recipient 60 years with Diabetes 20 years without Diabetes 20 years with Diabetes Lifespan without transplant* 4 years16 years9 years Lifespan with transplant* 9 years22 years16 years Incremantal survival 5 years6 years7 years * Median survival for this specific patient group (US data)

21. Examples of the consequences of allocation trade-offs Recipient 60 years with Diabetes 20 years without Diabetes 20 years with Diabetes Lifespan without transplant* 4 years16 years9 years Lifespan with transplant* 9 years22 years16 years Incremantal survival 5 years6 years7 years * Median survival for this specific patient group (US data) Allocation to the most urgent patient (maximize waiting list survival)

22. Examples of the consequences of allocation trade-offs Recipient 60 years with Diabetes 20 years without Diabetes 20 years with Diabetes Lifespan without transplant* 4 years16 years9 years Lifespan with transplant* 9 years22 years16 years Incremantal survival 5 years6 years7 years * Median survival for this specific patient group (US data) Allocation to the patient with best outcome (maximize post transplant survival)

23. Examples of the consequences of allocation trade-offs Recipient 60 years with Diabetes 20 years without Diabetes 20 years with Diabetes Lifespan without transplant* 4 years16 years9 years Lifespan with transplant* 9 years22 years16 years Incremantal survival 5 years6 years7 years * Median survival for this specific patient group (US data) Allocation to the patient largest benefit (maximize incremental survival)

24. The benefits of international cooperation

25. Benefits of international cooperation in organ transplantation Preventing organ loss Addressing the needs of special patient groups Improving the outcome of organ transplantation International harmonization of activities in organ donation and transplantation

26. Benefits of international cooperation in organ transplantation Preventing organ loss Addressing the needs of special patient groups Improving the outcome of organ transplantation International harmonization of activities in organ donation and transplantation

27. Transplanted organs per donor in countries with less than 15 Mill inhabitants ET vs. countries without multinational collaboration ET countries < 15 Mill population EU countries < 15 Mill population not multinational Deceased donors813 (19,3 pmp)1061 (15,6 pmp) Multi-organ donors 78,7%57,3% Tx kidney p.d.1,741,67 Tx liver p.d.0,760,51 Tx heart p.d.0,270,20 Tx lung p.d.0,280,07 Tx pancreas p.d.0,130,07 Newsletter transplant, September 2010

28. Estimating the increase in donor organs with better use of available donor organs If the use of donor organs in EU countries with a population of < 15 Mill (currently without established international collaboration) would be similar to that of the small ET countries, the number of available donor organs would increase by: ■ 88 kidneys ■ 265 livers ■ 89 hearts ■ 222 lungs ■ 68 pancreata This is a total increase of 732 organs or 2 organs per day without any increase in the number of utilized donors / donation rates pmp

29. Benefits of international cooperation in organ transplantation Preventing organ loss Addressing the needs of special patient groups Improving the outcome of organ transplantation International harmonization of activities in organ donation and transplantation

30. General organ allocation sequence Eurotransplant International HU (Accepted) Combined Organs Elective Other Organ Exchange Organizations National HU Eurotransplant

31. General organ allocation sequence Eurotransplant International HU (Accepted) Combined Organs Elective Other Organ Exchange Organizations National HU Eurotransplant

32. n=201 (16%)n=1053 (84%) Waiting time HU Liver-transplant First HU Liver-Tx [n=1254] Pediatric (<16 yrs) Adult (16+ yrs) Median waiting time: 2 d (both groups)

33. Organ allocation - Kidney Highly Immunized - Acceptable Mismatch (AM) – ABO compatible ETKAS Point Score System including HU : ABO Identical ADHB/L Pediatric donor (< 16yrs) recipients with status pediatric ABO identical NLSLO 0 HLA Mismatches (“full house”) ESP/ESDP ABO identical HR

34. Organ allocation - Kidney Highly Immunized - Acceptable Mismatch (AM) – ABO compatible ETKAS Point Score System including HU : ABO Identical ADHB/L Pediatric donor (< 16yrs) recipients with status pediatric ABO identical NLSLO 0 HLA Mismatches (“full house”) ESP/ESDP ABO identical HR

35. Procedure AM Program HLA typing of every potential donor is introduced in ENIS. Recipient is selected on the basis of compatibility of the donor with the patient’s HLA-A,-B and -DR antigens in combination with acceptable mismatches.. In case of a compatible donor: mandatory shipment of the kidney to recipient center.

36. Claas et al. Transplantation, 2004

37. Benefits of international cooperation in organ transplantation Preventing organ loss Addressing the needs of special patient groups Improving the outcome of organ transplantation International harmonization of activities in organ donation and transplantation

38. Probability of dying on the liver waiting list or removal due to clinical deterioration Elective liver-tx candidates, ET Jan 2002 – Jun 2009

39. Organ allocation - Kidney Highly Immunized - Acceptable Mismatch (AM) – ABO compatible ETKAS Point Score System including HU : ABO Identical ADHB/L Pediatric donor (< 16yrs) recipients with status pediatric ABO identical NLSLO 0 HLA Mismatches (“full house”) ESP/ESDP ABO identical HR

40. Role of HLA-matching for graft survival after kidney transplantation CTS Newsletter 2004:1 6.2 yrs. difference

41. 100%10073total 0,4%446 2,4 % 2445 10,5 % 10554 30,2%30433 26,6 % 26792 8321 2176 0 Percentage No. of transplantations No. of mismatches 21,6 % 8,3 % HLA-matching in kidney transplantation Eurotransplant 2000-2004, non-ESP patients

42. Impact of kidney organ exchange on selected patient groups Eurotransplant 01.01.2002 -31.12.2006

43. Impact of kidney organ exchange on selected patient groups Belgium, 01.01.2001 - 31.12.2005

44. The challenges of international cooperation

45. Challenges of international cooperation in organ transplantation International harmonization of allocation rules Logistical challenges including limitation of ischemic time Balancing of organ exchange

46. Challenges of international cooperation in organ transplantation International harmonization of allocation rules Logistical challenges including limitation of ischemic time Balancing of organ exchange

47. Examples of the consequences of allocation trade-offs Recipient 60 years with Diabetes 20 years without Diabetes 20 years with Diabetes Lifespan without transplant* 4 years16 years9 years Lifespan with transplant* 9 years22 years16 years Incremantal survival 5 years6 years7 years * Median survival for this specific patient group (US data) Allocation to the patient largest benefit (maximize incremental survival)

48. National Competent Authorities Allocation development – role of ET ET-Board EC ISWG OPC ETKAC ELIAC EThAC EPAC FC TTC ET Council ET-Office „Recommendations“ for approval „Guidelines“ for implementaion „Policies“ Control Support Data collection and -analysis etc. Allocation Allocation- Development

49. General organ allocation sequence Eurotransplant International HU (Accepted) Combined Organs Elective Other Organ Exchange Organizations National HU Eurotransplant

50. Leiden Eurotransplant liver allocation policy Countries with central MELD-based allocation as of 16.12.2006 Patient-oriented, central MELD-based allocation Center-oriented, local allocation

51. Challenges of international cooperation in organ transplantation International harmonization of allocation rules Logistical challenges including limitation of ischemic time Balancing of organ exchange

52. Ischemic time kidney transplantation Local/regional vs. national vs. international allocation 12,4 h 15,8 h 18,1 h 19,5 h

53. Ischemic time kidney transplantation Local/regional vs national vs international allocation Germany 12,4 h 15,8 h 18,1 h 19,5 h

54. Ischemic time kidney transplantation Local/regional vs national vs international allocation

55. Challenges of international cooperation in organ transplantation International harmonization of allocation rules Logistical challenges including limitation of ischemic time Balancing of organ exchange

56. Organ donation – Eurotransplant 2012 -0,3 / -1,0% -1,9 / -13,2% +0,7 / +2,1% +1,8 / +13,5% +7,1 / +48,3%

57. The concept of self-sufficency and organ balancing Self-sufficiency in organ transplantation means the adequate provision of transplantation services and supply of human organs from within a given population, to satisfy the organ transplantation needs of that population In practice, populations pursuing self- sufficiency are likely to correspond to the citizens or residents of nation states. In the context of multinational organ exchange organizations like Eurotransplant the concept of self-sufficiency therefore typically includes a balancing system between countries

58. International organ exchange and balancing within Eurotransplant Basic principles Prevent cross-border organ exchange when medically not indicated by giving preference to national (regional/local) allocation ■ Kidney: distance points ■ Non-renal organs: National allocation except for international mandatory exchange and prevention of organ loss Ethical basis: short ischemic time leads to better transplant outcome

59. Origin of transplanted donor organs Eurotransplant 01.01.2001 – 31.12.2005

60. International organ exchange Basic principles of balancing International organ exchange imbalances (in spite of the preferentially national allocation system) are addressed by organ specific balancing systems Different mechanisms for balancing Aim of the mechanisms used is a “reasonable balance” between “import” and “export” of donor organs per country

61. Summary An organ allocation system should be transparent, objective and reliable The allocation rules should have a solid ethical foundation and should be based on evidence-based medical criteria Continuous monitoring of the allocation rules and their impact is essential International cooperation helps addressing the needs of special patient groups and is in line with the self-sufficiency principle Without access to the waiting list the best allocation cannot help