Organ Transplant Systems in the EU : A selected overview

Transcription

1 Organ Transplant Systems in the EU : A selected overview

2 This document represents the output of Work package 4 of COORENOR project (deliverable 4). This Deliverable arises from the COORENOR project (Grant agreement n ) which has received finding from the European Commission in the framework of the Health Programme. The sole responsibility lies with the author and the Executive Agency for Health and Consumers is not responsible of any use that may be made of the information contained here.

3 CONTENT TABLE Introductive words The selected overview of EU organ transplant systems under the COORENOR project P3 Transversal overview P4 Transplant systems Transplant systems and activities P4 P5 Favoured arguments regarding the choice of indicators P9 Safety management P10 European Directive 2010/53/EU : setting standards of quality and safety of human organs intended for transplantation Donor medical history and organ characterization P10 P10 Bottom line and key points P14 1

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5 The selected overview of EU organ transplant systems under the COORENOR project COORENOR was a three-year project co-funded by European Union in the framework of the Public Health Programme. COORENOR Project aimed to establish a Coordinated Network between national programmes existing in the field of organ transplantation, taking into account some major issues such as deceased donation, kidney living donation and organ exchanges. Taken altogether, these activities shall foster coordination of Eastern and Western European Countries, having all different approaches and programs to address issues related to organ donation and transplantation. This EU overview presents the analysis of organ transplant programmes and organisational systems that were developed in European countries, building on the main outcomes of ALLIANCE-O Project ( ). Such overview has proven to be very useful in deepening the knowledge of running programs and practices, but was limited to seven Member States: France, Spain, Italy, United Kingdom, Hungary, Germany and Portugal, which are additionally more than likely to have developed or modified their system since. Furthermore, in 2010, the introduction of the European Directive 2010/53/EU set standards of quality and safety of human organs intended for transplantation, that Member States had to comply with before the 27 of August Therefore, reporting on potential problems foreseen or encountered by Member States during transposition or implementation stages was of interest as well. As first step, a targeted questionnaire was distributed to Competent Authorities for organ donation and transplantation of all Member States and to official representatives (contacts provided by DG SANCO) for non EU countries (Norway, Moldova and Switzerland), candidate countries and potential candidate countries (see figure 1 for details). Figure T1 : Mapping of countries that replied to the questionnaire : i) Member States except Denmark, Ireland, Luxembourg, Germany and Malta (22 Member States out of 27), ii) candidate countries: Croatia and Macedonia, and iii) potential candidate country: Albania. This overview also included answers collected from Norway, Switzerland and Moldova. Germany is hatched since although not answering the questionnaire, country overview was reviewed by Competent Authority (Ministry of Health) and national Transplant Agency for organ transplantation from deceased donors (Deutsche Stiftung Organtransplantation). Countries were given the opportunity to review their profile. Overviews are based on common information that was available for all Member States (MS), on answers to the questionnaire, main actors' profile, existing legislation, transposition and implementation of the Directive 2010/53/EU, Eurobarometer survey on organ donation and transplantation, information provided by official website and possibly national publications. National panoramas were designed in order not to overlap with other previous or on-going EU projects or working groups (e.g. Technical working group on organ donation and transplantation indicators piloted by DG SANCO, ODEQUS). 3

6 1. TRANSVERSAL EU OVERVIEW Transplant systems In these overviews, Organ transplant programmes and organisational systems are described at supranational/national/regional and local level considering key operational steps of each donation, allocation, transplantation and follow-up sub-process; the position and profile of the main actors responsible for each key step of these sub-processes is defined as well. Moreover, key steps were considered under different aspects of quality programmes such as training, procedures (to be followed), guidelines (recommendations) and audits (evaluations, inspections). Additionally, National panorama also includes an extrapolated and simplified scheme of operational key steps designing each Transplant system (figure 2). Local Hospital/retrieval site Donor Consent approach (MD, Tx C) Regional Transplantation Centre Recipient Clinical Follow-up (MD, TxC) Identification (MD) Donor maintenance (MD) Donor Validation (MD, Tx C) Coordination of Organ proposal (Tx C) # Organ acceptance (MD) Allocation Regional Transplant Coordinators Regional Delegated body* Supranational Recipient Follow-up Registry (A) (B) Local Hospital/retrieval site Donor Local Transplantation Centre Recipient Clinical Follow-up (MD) Identification (MD) Consent approach (MD) Donor maintenance (MD) Donor Validation (MD) Organ Acceptance (S) Allocation # Regional coordination Transplantation Agency Delegated body* Regional National Supranational (C) Figure T2: Example of simplified operational scheme of four different MS (A, B, C and D) transplant system and main organisational and responsibility levels. MD: Medical Doctor; PhD: doctor in Science or a scientific expert; S: Surgeon; Tx C: Transplant Coordinator. #: The coordination of organ proposal stands for a common action of actors involved. (D) Altogether, the EU overview shows wide organisational and operational practices among Member States (22 MS) regarding practical approach from donation to follow-up sub-processes. Analysis reveals that the majority of the operational steps selected are either mainly organized at National level (scheme B and D), or mainly at regional (scheme A and C) or local level (or even sometimes at supranational level) but combined with the national level. 4

7 These simplified schemes of transplant systems were designed to facilitate understanding and to seize our differences at first sight; additionally, along with information gathered, each country overview is aiming at being useful not only for mutual understanding but also for any country starting up a given transplantation programme or about to redesign an existing one. It is noteworthy to highlight that each country developed its own system according to a specific environment, given needs and resources. As a consequence, this selected overview of organ transplant systems in EU does not aim at judging, but could rather prove useful for any country starting up a given transplantation programme or about to redesign an existing one and to inform on where to seek a specific expertise; any country/region might benefit from re-examining its own system in the light of these different models. Transplant systems and activities Acknowledging that each country developed its own system according to a specific environment, they are different in practices but also in sizes (number of hospitals performing Transplantations and transplant teams and programmes, see figure 3 and 4) and regarding transplantation activities (figure 5). Figure T3 : Number of Hospitals performing transplantation in 2010 (including those authorized for such activities but that were non-active that year). The map 1 includes countries having answered the questionnaire: i) 22 Member States out of 27, and Germany, ii) candidate countries: Croatia and Macedonia, and iii) potential candidate country: Albania. Among non EU countries are: Norway, Switzerland and Moldova. 1 Agence de la biomédecine, COORENOR, 2012, ESRI. 5

8 Figure T4 : Number of Transplant teams/programmes in 2010 (including those authorized for such activities but that were non-active that year). The map1 includes countries having answered the questionnaire: i) 22 Member States out of 27, and Germany, ii) candidate countries: Croatia and Macedonia, and iii) potential candidate country: Albania. Among non EU countries are : Norway, Switzerland and Moldova. Figure T5 : 2010 Transplantation activities (transplantation performed, including all combinations). The map includes countries having answered the questionnaire: i) 22 Member States out of 27, and Germany, ii) candidate countries: Croatia and Macedonia, and iii) potential candidate country: Albania (hatched, no data available). Among non EU countries are: Norway, Switzerland and Moldova (no transplantation activity in 2010). The different figures on the health resources allocated to the Transplantation activity (number of hospitals and transplant teams and programmes) and the reported level of activity show variations. In this regard, logistical issues were reported as a possible limitation of practices that would be likely to be increased by a greater level of resources within a single hospital (e.g. more teams available night and day for hearts transplantations) 2. Considering 2010 raw data, when comparing the five MS reporting higher transplantation activities (i.e. DE, FR, IT, ES and UK 3 ), those MS have respectively averages of 3, 1.8, 2.6, 2.3, and 1.8 transplant teams and programmes per hospital, and averages of 113.4, 71.9, 71.5, 77.2 and transplantations per hospital 2 Zaroff et al., Maximizing Use of Cardiac Donors, Circulation, 2002, DE: Germany, FR: France, IT: Italy, SP: Spain, UK: United Kingdom. 6

9 respectively. Comparing these figures suggests that the level of transplantation activities cannot simply be a direct consequence of the multiplication of teams and transplant programmes in a single hospital. To go further, FR and UK that both have an average of 1.8 transplant teams and programmes per hospital, show a different level of transplantation activity (and average of transplantation activity) per hospital. The very same year, both countries had for all organs 9 teams specifically dedicated to paediatrics transplantations, and this latter activity for kidneys accounted for 3.7% of the UK kidney transplantations and for 2.2% in FR. Furthermore, FR has roughly twice as much kidney transplant teams and programmes (adults and paediatrics) than UK but respective kidney transplantation activities reported for 2010 were of 2892 and Transplant teams and programmes specificity (organ considered) and distribution (adults and paediatrics) are to be taken into account as a partial explanation for EU discrepancies but are more than likely to not be the sole explanation. Of course, the flow of the overall system is also highly dependent on the procurement activity and so on the number of (active) hospital performing organ retrieval. Interestingly, the country (DE) showing the higher level of transplantation activity is also the one having the largest number of hospitals performing organ retrieval since in this country all hospitals can perform organ procurement (i.e in 2010 for 1296 actual deceased organ donors including 87% of multiorgan donors). However, in 2010 FR reported 160 hospitals proceeding with organ recovery and UK above 200, having the very same year reported 1538 (including 86.4% of multiorgan donors) and 1015 (including 72.3% of multiorgan donors) actual deceased donors respectively. This brief examination shows that analysing the efficiency of transplant systems is not so straightforward. Nevertheless, a hypothesis for discrepancies regarding those figures could lie in the distribution of deceased and living donors as shown for kidney transplantations in figure 6. Indeed, DE, FR, IT, ES and UK respectively reported that in 2010, 22.6%, 9.8%, 10.7%, 10.8% and 37.7% of kidney transplantations were performed thanks to a living donation, that is to say 1026 kidneys transplantations out of 2724 in UK and 283 out of 2892 for FR. FR has roughly twice as much transplant teams and programmes compared to UK, for twice as much kidney transplants from a deceased donor. But since 26% of transplantations in UK are performed thanks to a living donor for about 6 % in FR, transplant activities in UK are higher (activity per hospital authorized for transplantation) simply because transplant activities from living donors are higher. Living donations follow paths in the transplant system that are different from the one followed by deceased organ donations and shall then increase kidney (and liver to a lesser extent) transplantation activities without overloading processes. Living donations are less demanding in terms of resources and are planned activities whereas deceased donations have to be performed on a 24/24 basis. Additionally there is no EU consensus on the definition of Transplant programme and transplant team; as a consequence both terms entail different resources. Despite all above organisational and activity differences, most countries started to develop their transplant programme with kidney transplantations, which still remain nowadays the main activity of transplantation. In accordance, for 2010 activities, out of the transplantations that were performed in the EU 27, (62%) were kidney transplantations. Among those transplantations, more than half were performed thanks to a kidney given by a deceased donor in 25 MS and at least 75% of these kidney transplantations could be performed thanks to a deceased donation in 21 MS (see figure 6). 7

10 Transplantation from a living donor Transplantation fron a deceased donor 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2010 distribution of deceased and living donors in kidney transplantation AT BE BG CY CZ DK EE FI FR DE GR HU IR IT LV LT LU MT NL PL PT RO SK SI ES SE UK Figure T6: Distribution (shown as percentage) of deceased and living kidney donors for 2010 transplantation activity in the EU 27. Data collected from the 2011 Newsletter Transplant. In the line of benchmarking Transplant systems, and selecting indicators for the transplantation sub-process, displaying Transplantation activities versus patients registered on the waiting list (figure 7 for kidneys), to illustrate the number of candidates per organs (regardless to matching), could be worthwhile considering Candidates per kidney Number of candidates per kidney AT BE BG CY CZ DK EE FI FR DE GR* HU IR IT LV LT LU* MT NL PL PT RO SK SI ES* SE UK Figure T7: EU 27 overview of candidates per kidney in Histogram shows the ratio between Kidney transplantation activities (including all combinations) and total candidates for kidney transplantation (the sum of patients included for the first time on the kidney waiting list in 2010 and the patients awaiting for a kidney transplantation by the 31 rst of December 2009) 4. *: data not fully available. The ratio between kidney transplantations versus the total of candidates on the waiting list for a given year reflects the access to transplantation for patients suffering from end-stage renal disease (e.g. used in France, as an indicator of the transplant system along with patients' median time on the waiting list). This ratio reflects the gap between kidney demand and offer (transplantation). The higher this ratio is, the more limited is the access to transplantation. Indubitably, caution should be given to the interpretation of such indicator since in fact only active and transplantable patients should be considered (and not total candidates); moreover, the registration policy on the waiting list is quite heterogeneous among the medical community of professionals, and additionally, the management of the waiting list which can be conducted at the local or regional or at the best at a national level shall also be taken into account. Since most transplantation activities in EU are carried out from a deceased donor, this EU overview is not only presenting the donation and retrieval system in place, but also the level of organ donation and retrieval activities. Indeed, the retrieval rate can also be used as an indicator (providing that data are available) to estimate the efficiency and organisation of the system, especially when comparing organ recovered versus transplanted. It contributes to reflect on the performance of the system in place, together with hospitals 4 Newsletter Transplant 2010 and

11 active in organ donation and retrieval. All sub-processes upstream from transplantations can have an impact on transplantations activities. It would have been more interesting to analyse the efficiency of the donation sub-process according to potential, possible, actual and utilized donors 5, however these data were not available for all Member States. As a consequence, other indicators were chosen in order to be able to benchmark and analyse Transplant systems. Favoured arguments regarding the choice of indicators An indicator can be defined as a parameter used to specify the level of completion of a given operation. To be relevant, a chosen indicator not only requires a precise, clearly stated and commonly shared definition, but also to be actually used to monitor or compare a key process or action. Additionally, users must be aware of analysis limitations when manipulating indicators, especially in respect to the case-mix and subgroups included in the pool of data (age, gender, organ from a deceased or living donor, etc.). Results from various EU projects (ALLIANCE-O, EFRETOS, ODEQUS, COORENOR...) already showed wide practices among Member States regarding practical approach and followed criteria from donation to allocation, transplantation and follow-up sub-processes. As mentioned previously, criteria for admissions on waiting lists widely varies between Member States, as a consequence the number of patients registered on waiting lists was not considered as relevant at EU level, nor a shortage indicator such as the median time of patients on the waiting list. Concerning donation, the donor pool is quite often displayed as actual deceased donors per million inhabitants (pmp) 6. However, for the effectiveness of organ procurement systems, an evaluation from a living perspective would rather be a biased approach since it does not take into consideration mortality rates, neither organ-specific donation criteria, nor the low probability of devastating brain injury 7. Optimal indicator would have been the ratio of actual deceased donors (from whom at least one organ was recovered) to the in-hospital recorded cerebral death diagnosis and cardiac arrests. Unfortunately these latter figures are neither collected nationally nor available for all Member States. Actual Deceased organ donors deaths Actual Deceased Organ Donors per 1000 deaths in the EU AT BE BG CY CZ DK EE FI FR DE GR HU IR IT LV LT LU MT NL PL PT RO SK SI ES SE UK Figure T8: Number of Actual deceased Donors (donors from whom at least one organ was retrieved, including non-heart beating donors) per thousand national deaths (<70 years old) through the EU, for the year Potential: a person whose clinical condition is suspected to fullfil criteria for donation after circulatory or brain death; eligible: fulfill the death criteria and is medically suitable for organ donation; actual : from whom at least one organ was recovered; and utilized : from whom at least one organ has been transplanted. Definition deriving from Transplant International 2011;24: Newsletter Transplant 7 A practical approach to evaluate the potential donor pool and trends in cadaveric kidney donation. Ojo AO, Wolfe RA, Leichtman AB, Dickinson DM, Port FK, Young EW. Transplantation Feb 27;67(4): Newsletter Transplant 2011 for Actual deceased organ donors figures and Eurostat data base for 2010 national Deaths. 9

12 Therefore, for a more meaningful estimation of performances and organisation of the system, data regarding post-mortem organ donation are shown as actual deceased donors per thousand national deaths (deaths <70 years old ; figure 8). Safety management European Directive 2010/53/EU : setting standards of quality and safety of human organs intended for transplantation Directive 2010/53/EU was notably set in order to increase security and quality of organ donations and transplantation, to fight against trafficking and to harmonise practices within and between Member States. This Directive aims in particular at setting provision for an authorization system dedicated to Hospital performing organ retrieval and for transplantation establishments as well, patients and donor follow-up, data reporting, traceability and biovigilance systems. Additionally, the Directive also calls for the nomination of a Competent Authority in each Member States: "Member States shall designate one or more competent authorities" (article 17), Competent Authority being defined in article 3 (b) as : "an authority, body, organisation and/or institution responsible for implementing the requirements of this Directive". As stated in point 24 of the Directive "The competent authorities of the Member States should have a key role to play in ensuring the quality and safety of organs during the entire chain from donation to transplantation and in evaluating their quality and safety throughout patients' recovery and during the subsequent follow-up". This Directive was introduced in July 2010 and Member States had to comply with it before the 27 of August Therefore, this overview opportunity was also seized to report on potential problems that were either foreseen at that time or encountered by Member States during transposition or implementation stages. Donor medical history and organ characterization Evaluation of donor and organ characterization for suitability is based on the collection of past and recent information on the medical health status, laboratory tests results notably for transmissible diseases, and on physical examination. The aim is to ensure that the recipient would not be exposed to unacceptable/ unidentified risks. Indicators for the assessment of donor suitability among the EU22 MS having replied to the questionnaire are compiled in figures 9, 10, 11, 12, 13. Transversal EU results for the 22 MS (figure 9) show that 23 medical inquiries are common to more than half of the MS included in the survey and that 19 are common to more than 75% of the 22 MS. Importantly, 15 are common to 90% of the 22 MS. Out of the 5 medical criteria that were not systematically inquired, PSA (prostate specific antigen, item 18) dosages are usually recommended as systematic only for men older than 50 years old. 10

13 Systematic inquiries Out of 22 MS 1) Anamnestic information available 21 2) Risk factors for HIV/hepatitis 21 3) Previous Infectious Diseases 20 4) Illicit substance abuse 21 5) Neoplastic Diseases 21 6) Familiar history of malignancies 16 7) Surgical interventions 21 8) Pregnancy tests 9 9) βhcg 7 10) History of recent miscarriages 7 11) Cardiovascular diseases 21 12) Pulmonary diseases 20 13) Liver diseases 21 14) Renal disorders 21 15) Diabetes 21 16) Autoimmune disorders 19 17) Hypertension 21 18) PSA 8 19) Dyslipidemia 12 20) Alcohol consumption 20 21) Smoking status 20 22) Diseases of unknown etiology 17 23) Radiation exposure 8 24) Recent history of immunisation with live vaccines 14 25) History of blood transfusion 20 26) Congenital/inherited disorder 19 27) Risk of transmitting prion disease 14 28) Neurodegenerative diseases 18 Figure T9 : Donor medical history. Table : items systematically enquired; coloured cells: not common to less than half of the 22 MS having answered the questionnaire. Graph: illustration of table results. As a complement, in order to fully characterize the donor, morphological tests are essentials (figure 10). ECG and chest radiography are systematically performed by almost all 22MS and abdominal and pelvic ultrasonographic examination by 68% of them (15 MS out of 22). Furthermore, more than half of the EU22 carry out CT scan, echography and Coronary angiography under specific conditions (second column). CT scan allows to perform morphological and vascular assessments and to detect possible tumours. This widely informative procedure is mostly convenient when concomitant to the cerebral angiography that can be used for the diagnosis of cerebral death. As for Coronary angiography, its relevance has been demonstrated so far only for population showing a risk of coronaropathy 2. Morphological tests performed Yes Yes, under specific systematically conditions No 1) ECG ) Chest radiography ) CT scan/ body scan ) Echocardiography ) Coronary angiography ) Abdominal and pelvic ultrasonographic examination Figure T10 : table listing additional morphological tests that could be performed. Among the 4 MS reporting never performing Coronary angiography, one is not carrying out any heart transplantation activity, 2 perform echocardiography (under specific conditions, which could be for heart donation) and one systematically analyses troponin and CPK levels. 11

14 For the assessment of organ and donor suitability, some virological statuses and protein levels are also either compulsory or of importance in order to meet safety and quality criteria, some of the most key indicators are listed in figure 11. Tests systematically performed Out of 22 MS 1) Anti HIV Ab 21 2) HIV (PCR/NAT) 13 3) Anti HCV Ab 22 4) HCV (PCR/NAT) 14 5) HBs Ag 22 6) Anti HBs Ab 17 7) Anti HBc Ab 21 8) HBV (PCR/NAT) 13 9) HDV if patients HBs Ag positive 7 10) Syphilis (TPHA / VDRL) 21 11) Anti CMV (IgG and IgM) 20 12) HSV-1 (IgG) 6 13) HSV-2 (IgG) 5 14) EBV (Anti-VCA Ab and Anti-EBNA Ab) 13 15) VZV (IgG) 5 16) Toxoplasma (Antibody) 16 17) Troponin 11 18) CPK 12 19) Anti HTLV Ab 8 20) Malaria 1 21) Rabies 0 Figure T11 : Medical tests systematically performed. Table : items systematically enquired; coloured cells: not common to less than half of the 22 MS having answered the questionnaire. Graph: illustration of table results. Results show that 14 of the listed medical tests systematically performed are common to more than half of the MS included in the survey and that 7 are common to more than 75% of the 22 MS. Besides, 6 are common to 90% of the 22 MS. Out of the 7 listed medical tests that were not systematically performed (coloured cells in the table) some tests are linked to prevalence proportion within MS (e.g. malaria and HTLV), and some others can be linked to either extended criteria at case by case level, and likely to be considered in the light of contraindications applied including dedicated legislation in place (e.g. HTLV1 in France) and the balance of benefice-risk for the recipient. As a complement to the 21 benchmarks listed in figure 11, supplementary tests could be run (see table in figure 12). Do you perform tests for emerging diseases? Yes, under specific conditions Yes systematically Relative contraindication/ in specific conditions Absolute contraindication 1) West Nile fever ) Dengue fever ) Chikungunya fever Figure T12 : table listing additional medical tests that could be performed. The majority (about 3/4) of the 22 MS does not systematically test for West Nile, dengue or Chikungunya fevers. Since these emerging diseases are limited to specific areas, tests are only performed under suspicion and in countries of prevalence (second column of the table in figure 12). In this regard, the biovigilance system in place is crucial when facing increase of emergent virus which spread out through Europe. No In doubtful cases, 15 MS out of 22 (68%) have histopathologists or experts in infectious diseases to turn to for a second opinion, should they seek advices (column Yes in the table of figure 13). 12

15 If yes, are they? Yes Available 24h/day & 7/7 1) Histopathologist ) Oncologist ) Coroner 8 7 4) Expert in Infectious diseases ) Others 4 4 Figure T13 : Table listing experts which could possibly be available should a second opinion be necessary. Others being experts in rare diseases, haematologist, donor coordinator, immunologist, liver surgeon, nephrologist, lung specialist, or cardiologist. In most countries (more than half of the 22 MS), these experts are not available on 24/7 basis (last column of the table), which is not helping in the decision-making process that may be difficult in specific situations, even in rare or complex ones. Nevertheless, the risk of transmission is a critical issue in this field and should be supported on 24/7 basis by available experts. Risk levels were already defined in ALLIANCE-O as : 1. Unacceptable risk (absolute contraindication): the donor is not suitable for transplantation. 2. Increased but acceptable risk : cases where transmissible organisms or diseases are identified during the evaluation process of the donor, but organ utilization is justified by the recipient specific health situation or by the severity of his/her clinical conditions. 3. Calculated Risk (referring to protocols for expanded criteria donors) : presence of transmissible diseases, but the transplantation is allowed for a recipient with the same disease or with a protective serologic status independently from the severity of his health conditions. 4. Not assessable risk : the evaluation process does not allow an appropriate risk assessment for transmittable diseases. 5. Standard Risk : the evaluation process did not identify any transmittable disease. Experts could be consulted if any doubt arises (second opinion) 9. In this regard, although costly, 24/7 availability of experts for second opinion on doubtful cases is crucial. 9 WP4- Deliverable 4.2; and ALLIANCE-O White Paper. 13

16 27. BOTTOM LINE AND KEY POINTS Bottom line The COORENOR Project aimed to establish a Coordinated Network between national programmes existing in the field of organ transplantation and mutual understanding appears to be compulsory to foster coordination of Eastern and Western European Countries. Since each country developed its own system according to a specific environment, given needs and resources, it was of importance to describe the different approaches and programmes that have been developed to address issues related to organ donation and transplantation and to choose indicators to specify the level of completion of key process or action (with the limitation to potential case-mix and subgroups included in the pool of data). Organ shortage (inadequate supply) is regularly pointed out as the limiting factor of organ transplantation. As a partial solution, some MS have expanded donor criteria, developed strategies such as swapped/paired living kidney donations (that are handled / managed through different path). But when looking at national death rates and so to possible donor raw data although keeping in mind that the real potential of donor lies in persons dying in ICU 10 which are properly/ adequately equipped to ensure donor maintenance could it firstly be that Transplant systems have not reached their full potential yet? To optimize organ demand and supply many actions can be implemented. To start with, to increase donation : better detection of potential and possible donors, and regardless of donation policies (soft presumed consent, informed consent etc. ) : better practises regarding family approach, etc. Actually, regarding this donation sub-process, in the recent years most advanced countries in the field have developed organisational processes and strategies for a better detection of donors by appointing "key Donation Personnel" (donation coordinators). So, the fact that Transplant systems could be more efficient is not news to anybody. However, doing so, each MS could wonder if the transplantation sub-process would follow and cope with a higher level of activity? Is there enough transplant programmes (and so teams) to perform surgeries that as a consequence would be required? Obviously, limitations to the development of transplant systems are more than likely to be due to a lack of finances (which include lack of human and technical resources), since those systems are highly dependent on available resources for the health care system in place at the national (or regional) level, although a direct link between the level of health resources and transplantation outcomes has not been demonstrated so far. Concerning quality and security programmes in this domain, common transplantations outcomes or graft or patients' survival rates should after all be the keystone of any analysis of EU transplant system efficiency. Such indicator could disregard individualities and overcome discrepancies. Unfortunately, such an overview was not possible because of a data shortage at EU level. European Directive 2010/53/EU: setting standards of quality and safety of human organs intended for transplantation Regarding the transposition of the Directive set for the 27 of August 2012 : out of the 22 MS having answered the questionnaire, 5 MS were having or foreseeing problems for transposition due to: i) a lack of finances (2 MS), ii) variations from national laws (2 MS), iii) a lack of human resources (4 MS) and/or to iv) a lack of technical resources (2MS). As for the Directive implementation, 4 MS out of 22 were having or foreseeing problems due to: i) a lack of finances (2 MS), ii) time frame and would experience a delay (1 MS), and/or to iii) a lack of human resources (3 MS). 10 Data not available for all MS 14

17 In the end, contrary to all expectations, more than half of the MS demonstrated delays in transposing. Key points As a final step, when most advanced in the COORENOR project, recommendations on further EU initiatives and future work in the field were to be issued Information collected and results generated by this survey analysis showed potential for improvement. As a driver for transplant systems development and upgrading : direct transfers of expertise (e.g. twinning activities) and tools sharing appear to be an easy and more cost-effective solution for the harmonization of EU practises and implementation of Directive 2010/53/EU. More precisely, regarding sub-processes, in order to increase the efficiency of various donation systems in place : Quality assurance programmes (donor detection procedures and /or appointing donor coordinators at local level) could be worthwhile implementing. As a complement to tackle the donation sub-process, when applicable, competent authorities should foster the implementation of recommendations and guides generated at EU level like the European Resuscitation Council Guidelines for Resuscitation 2010, and by the Council of Europe Recommendation No (2005) 11 of the Committee of Ministers to Member States on the role and training of professionals responsible for organ donation (transplant donor coordinators ), or Recommendation No (2006) 16 of the Committee of Ministers to Member States on quality improvement programmes for organ donation. In addition, when dealing with deceased donors, rapid anatomopathological analysis should be possible when deemed necessary in order to lower the risk of transmitting diseases. Some other sub-processes should be addressed urgently such as the follow-up of living donors and recipients, and the evaluation of post-transplant results, in Member States not having dealt with these aspects so far. Importantly, Member States overviews also showed that audits are lacking in many subprocesses. Yet evaluation and audits are keystones to not only verify compliance but also to improve quality and safety of all activities. Taken altogether, data recording and so computerisation of all sub-process is a way to control, evaluate and ensure traceability. As a consequence EU Competent Authorities should take all the necessary actions to provide such transparency and to ensure full reporting. By promoting exhaustive data collection, it will become possible to evaluate transplantations, post-transplantation survival etc. Likewise, all Competent Authorities should endeavour the drafting of an annual activity report both for professionals and public at large. Notwithstanding that in parallel, it is of importance to communicate toward professionals, dialysis centres, patients and public at large both on organ donation and transplantation. To go further, collecting data at national level through a patient waiting list managed nationally, a national list of transplanted patients and follow-up, of transplanted organs, of living donors' follow-up, appear to be an additional step forward safety and quality. It is also of primary importance to have transparent allocation rules and procedures that are fully and duly followed, with a notification and data reporting as previously mentioned to a national organisation for allocation that can in turn verify that allocation was in accordance with national rules. So as to reach that goal, an IT tool is the only solution, a computerised and algorithm system for allocation ensures equity. In this regard, the drafting of EU recommendations concerning minimal criteria and optimal / extended criteria to be fulfilled could be advisable. In the line of action of the COORENOR project, a wider network of donor pool and of organ cross-border exchanges like the one developed shall be highly beneficiary especially for most urgent patients and patients difficult to match (i.e. hyperimmuzed, rare blood types, paediatrics); and to go further in the promotion of this network, it would be advisable to develop organ specific retrieval protocols (including technical requirements) to facilitate procedures in Member States and Centres unfamiliar with those procedures; and /or promoting 15

18 the set-up of a mobile procurement team; avoiding in the long term foreign teams accepting the organ to travel, along with organ preservation and packaging protocols. ACKNOWLEDGEMENTS This document was drafted by Candide Font-Sala, with the support of Marie Thuong, Florian Bayer (cartographer) and of colleagues from the Agence de la biomédecine including the biostatistical and evaluation department. The Agence de la Biomédecine would like to thank all participating countries for having answered the questionnaire, additional questions, and for their views on national profile. The Agence de la biomédecine would also like to thank the coordinators of the COORENOR project: the Italian national Centre for their professionalism and valuable input. Importantly, The Agence de la biomédecine would like to highlight that The European Commission, by cofinancing projects under the health programme, has already greatly contributed to the field of organ donation and transplantation (i.e. ODEQUS for audits implementation, EFRETOS regarding the set-up of follow-up registry). FOEDUS joint action, which is about to start, will develop further organ exchanges between EU countries. Thanks to financial support, the European Commission is promoting a better, safer and wider national and European landscape for organ donation and transplantation. 16

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