Cost-Benefit Analysis of Kidney Donation Systems and an Alternative System Proposal for Turkey

COST-BENEFIT ANALYSIS OF KIDNEY DONATION SYSTEMS AND AN ALTERNATIVE SYSTEM PROPOSAL FOR TURKEY

A THESIS SUBMITTED TO THE INSTITUTE OF SOCIAL SCIENCES OF YILDIRIM BEYAZIT UNIVERSITY

YAVUZ DEMİRDÖĞEN

IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN THE DEPARTMENT OF BANKING AND FINANCE

APRIL 2017

Approval of the Institute of Social Sciences

Asssociate Prof. Dr. Seyfullah Yıldırım Acting Manager of Institute

I certify that this thesis satisfies all the requirements as a thesis for the degree of

Doctor of Philosophy in Department of Banking and Finance.

Assoc. Prof. Dr. Ayhan KAPUSUZOĞLU Head of Department

This is to certify that we have read this thesis and that in our opinion it is fully adequate, in scope and quality, as a thesis for the degree of Doctor of Philosophy in Department of Banking and Finance.

Prof. Dr. Fuat OĞUZ Supervisor

Examining Committee Members Prof. Dr. Fuat OĞUZ (YBU, Economics) ______Assist. Prof. Dr. Erhan ÇANKAL (YBU, Banking and Finance) ______Assis. Prof. Dr. Fatih Cemil ÖZBUĞDAY (YBU, Economics) ______Assoc. Prof. Dr. Fetullah AKIN (Gazi Uni., Economics) ______Assist. Prof. Dr. Erkan GÜRPINAR (ASBU,Economics) ______

PLAGIARISM

I hereby declare that all information in this thesis has been obtained and presented in accordance with academic rules and ethical conduct. I also declare that, as required by these rules and conduct, I have fully cited and referenced all material and results that are not original to this work; otherwise I accept all legal responsibility.

Name, Last name: Yavuz DEMİRDÖĞEN

Signature :

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ABSTRACT

COST-BENEFIT ANALYSIS OF KIDNEY DONATION SYSTEMS AND AN ALTERNATIVE SYSTEM PROPOSAL FOR TURKEY

Yavuz DEMİRDÖĞEN

Ph.D., Department of Banking and Finance

Supervisor: Prof. Dr. Fuat OĞUZ

April 2017, 203 pages

This study analyzes the cost and benefit of the kidney donation system in Turkey through the analyses of the costs of hemodialysis and kidney transplantation. These analyses were made by using real data. Afterwards, a sensitivity analysis is made by the use of the results of the cost-benefit analysis. One other sensitivity analysis is made for the determination of the amount of the monetary incentive. Within the framework of this study, an alternative system for increasing organ donation rates is proposed which is based on the following three pillars: an opt-out system, a monetary incentive and a government monopsony.

Keywords: Cost-benefit analysis, organ donation, kidney transplantation, monetary incentive.

ÖZET

COST-BENEFIT ANALYSIS OF KIDNEY DONATION SYSTEMS AND AN ALTERNATIVE SYSTEM PROPOSAL FOR TURKEY

Yavuz DEMİRDÖĞEN

Ph.D., Department of Banking and Finance

Danışman: Prof. Dr. Fuat OĞUZ

Nisan 2017, 203 sayfa

Bu çalışmada, hemodiyaliz ve böbrek nakil maliyetleri hesapları üzerinden Türkiye’deki bağış sisteminin maliyet-fayda analizi yapılmaktadır. Bu analizlerde gerçek veriler kullanılmıştır. Yapılan maliyet-fayda analizinin sonuçlarıyla duyarlılık analizi yapılmıştır. Bir başka duyarlılık analizi de parasal teşvik miktarının tespiti için yapılmıştır. Bu çalışmanın ışığında organ bağışını artırmak amacıyla üçayak üstüne kurulan alternatif sistem önerisi yapılmıştır: zorunlu donor sistemi, parasal teşvik ve devlet monopsonisi.

Anahtar kelimeler: Maliyet-fayda analizi, organ bağışı, böbrek nakli, parasal teşvik.

DEDICATION

TO MY FAMILY

ACKNOWLEDGMENTS

I would like to extend my special thanks to;

…to my thesis advisor, Prof. Dr. Fuat OĞUZ for his guidance, support, encourager attitude and enlighten the path of every step whether it is a dead-end.

…the examining committee members, Assist. Prof. Dr. Fatih Cemil ÖZBUĞDAY, Assist. Prof. Dr. Erhan ÇANKAL, Assoc. Prof. Dr. Fethullah AKIN and Assist. Prof. Dr. Erkan GÜRPINAR for their precious contributions and criticisms.

…my friends and colleagues for their support and encouragements.

…Ayhan AYDIN for editing, proofreading and eliminating the deficiencies.

I would also like to extend my sincerest gratitude and appreciation to;

…my all family members for moral support to academic studies and for their invaluable love, support and encouragements.

…AND my beloved wife and precious daughters for their patience, encouragement and support at every time of my life.

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TABLE OF CONTENTS

PLAGIARISM ...... iii

ABSTRACT ...... iv

ÖZET ...... v

DEDICATION ...... vi

ACKNOWLEDGMENTS ...... vii

TABLE OF CONTENTS ...... viii

LIST OF TABLES ...... xii

LIST OF FIGURES ...... xiii

LIST OF ABBREVIATIONS ...... xiv

PART I: THEORY AND WORLD EXPERIENCE ...... 1

1. INTRODUCTION ...... 1

2. HISTORICAL DEVELOPMENT OF ORGAN TRANSPLANTATION ...... 6

2.1. Definition of Brain Death ...... 8

2.2. History of the Legal Status about Organ Donation ...... 10

2.3. History of Organ Transplantation in Turkey ...... 17

3. WHAT IS CHRONIC KIDNEY DISEASE (CKD)? ...... 20

3.1. Initial Symptoms of CKD ...... 22

3.2. Diagnosis of CKD ...... 23

4. SUPPLY AND DEMAND OF KIDNEY AROUND THE WORLD ...... 25

4.1. Supply of Transplantable Organs...... 32

4.1.1. Transplantable Organs...... 33

4.1.2. Approval of Next of Kin ...... 35

4.1.3. Legal Procedures ...... 36

4.1.4. Availability ...... 38

4.1.5. Organization ...... 38

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4.1.6 Time ...... 40

PART II: ECONOMICS OF KIDNEY DONATION ...... 42

5. DONATION SYSTEMS AROUND THE WORLD ...... 42

5.1. Deceased Organ Procurement Policies ...... 42

5.1.1. Presumed Consent ...... 43

5.1.2. Informed Consent ...... 44

5.1.3. Mandated Choice...... 45

5.1.4. Enforced Donor ...... 46

5.2. Monetary Incentive Mechanism Regimes ...... 46

5.2.1. Free Market System ...... 46

5.2.2. Government Monopsony ...... 48

5.2.3. Reimbursement System ...... 50

5.3. Future Delivery Market ...... 51

5.3.1. Opt-in Future Contract System ...... 51

5.3.2. Opt-out Future Contract System ...... 51

5.4. Living Organ Procurement Policies ...... 52

5.4.1. Policies Based on Monetary Incentives ...... 53

5.4.1.1. Government Monopsony ...... 53

5.4.1.2. Reimbursement of Living Donors ...... 55

5.5. Non-monetary Organ Allocation ...... 57

5.5.1. Pairwise Kidney Exchange...... 58

5.5.2. NEAD Chain and Domino Paired Donation ...... 59

6. ECONOMIC DIMENSION OF KIDNEY DONATION ...... 61

6.1. Donation In Terms of Basic Economic Theory ...... 61

6.2. Determinants of Supply ...... 63

6.2.1. Altruism ...... 63

6.2.2. Legal Regulations ...... 65

6.2.3. Effect of Healthcare System ...... 66

6.3. Determinants of Demand ...... 66

6.3.1. ESRD Patients ...... 66

6.3.2. Legal Regulations ...... 66

6.4. Effect of Monetary Incentives on Supply and Demand ...... 68

7. KIDNEY BLACK MARKET AND TRANSPLANT TOURISM ...... 71

PART III: TURKEY ...... 75

8. LEGAL REGULATIONS IN TURKEY ...... 75

8.1. Organ and Tissue Allocation Principles ...... 75

8.2. Donation and Transplantation from Living Donor ...... 76

8.3. Kidney Allocation Principles ...... 76

9. KIDNEY TRANSPLANTATION AND DONATION IN TURKEY ...... 79

9.1. Legal Status ...... 79

9.2. Change in the Last Decade ...... 83

9.3. Fundamentals of Selection Process and Urgency of Transplant Patients in General 86

10. COST ANALYSIS ...... 89

10.1. Cost of Dialysis in Turkey ...... 89

10.2. Cost of Transplantation in Turkey ...... 91

10.3. Comparison between Transplantation and Dialysis Costs ...... 93

10.4. Cost-Benefit Analysis of Kidney Transplantation in the World ...... 99

10.5. Cost Analysis of Hemodialysis ...... 100

10.6. Cost Analysis of Transplantation ...... 103

11. COST-BENEFIT ANALYSIS OF KIDNEY TRANSPLANTATION IN TURKEY ...... 107

11.1. Sensitivity Analysis ...... 109

11.2. Uncalculated Elements ...... 111

12. AMOUNT OF MONETARY INCENTIVE AND ITS EFFECTS ON KIDNEY DONATION IN TURKEY ...... 113

12.1. Kidney Transplantation and Dialysis in Turkey ...... 116

12.2. Economic Analysis of Monetary Incentive...... 117

12.3. Sensitivity Analysis ...... 121

12.4. The Benefits of Decreasing the Number of Patients on the Waiting List ...... 124

12.5. Encouraging Living Donation ...... 127

PART IV: RECOMMENDATIONS ...... 129

13. AN ALTERNATIVE PROPOSAL FOR KIDNEY DONATION SYSTEM IN TERMS OF SOCIAL WELFARE ...... 129

13.1. Governmental Regulations for Incentive Systems ...... 135

13.2. Evaluation of Applications around the World ...... 138

13.3 Discussion ...... 142

14. CONCLUSION ...... 146

15. REFERENCES ...... 149

16. APPENDICES ...... 178

Appendix 1: Details of Calculations ...... 178

Appendix 2: Briefing about Data Collection and Gathering ...... 180

Appendix 3: Calculation Data Set ...... 181

Appendix 4: Curriculum Vitae ...... 182

Appendix 5: Turkish Summary ...... 185

LIST OF TABLES

Table 1: Major legislative and regulatory landmarks and other requirements affecting organ procurement organizations (OPOs). Source: Howard et al. (2012) ...... 15 Table 2: Some articles from Turkish Law on harvesting, storage, grafting and transplantation of organs and tissue. Source: Haberal and Karaali (2005) ...... 18 Table 3: Five stages of chronic kidney disease as defined by KDOQI guidelinesa ...... 21 Table 4: Albuminuria categories of CKD...... 21 Table 5: Risk factors for chronic rejection ...... 26 Table 6: Kidney transplant from deceased donors 2014 ...... 28 Table 7: Kidney transplant from living donors 2014 ...... 29 Table 8: Worldwide actual deceased organ donors 2014 ...... 30 Table 9: Worldwide living organ donors 2014 (Source: IRODat Registry 2015)...... 31 Table 10: Transplantation quantities from living and deceased donors (2011-2015) ...... 84 Table 11: Costs of HD, PD, Tx from living and deceased donor for countries ...... 96 Table 12: Cost of a Hemodialysis Patient ...... 102 Table 13: The cost-benefit analysis of transplantation ...... 108 Table 14: Sensitivity analysis of change in donation, transplantation and waiting list figures ...... 110 Table 15: Change in number of transplantations according to VSL ...... 122 Table 16: The list of penalties imposed in countries. Source: Bilgel (2011) ...... 139 Table 17: List of donation systems around the world ...... 140

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LIST OF FIGURES

Figure 1: Distribution of organ donation from brain death and cardiac death in the U.S. .. 11 Figure 2: Major legislative and regulatory landmarks of organ donation and transplantation (U.S.) Source: Howard et al. (2012) ...... 14 Figure 3: Cardiovascular disease in CKD ...... 23 Figure 4: Elements of protocols recovering organs after cardiac death...... 34 Figure 5: WHO Guiding principles on Human Cell, Tissue and Organ Transplantation ... 39 Figure 6: Percentage of approval of different models of FI for LD in comparison to percentage of willingness to donate altruistically to a relative...... 56 Figure 7: Percentage of approval of different models of FI for LD in comparison to percentage of willingness to donate altruistically to a relative or a donation to a charity or getting priority in a waiting list in case one needs later an organ transplant...... 57 Figure 8: Historical evolution of kidney paired donation from its original proposal by Felix Rapaport to present. Source: Wallis et al. (2011, p. 2092) ...... 58 Figure 9: Schematic representation of exchange systems...... 60 Figure 10: Simplified graph of supply and demand ...... 62 Figure 11: Supply of kidney used normal conditions ...... 62 Figure 12: Number of patients and transplants between 2011 and 2015...... 63 Figure 13: The quantity of patients added to the waiting list (yearly basis) ...... 85 Figure 14: The transplantation data and the graph of Turkey ...... 86 Figure 15: Percent change in total number of transplantations ...... 124

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LIST OF ABBREVIATIONS

BMI : Body Mass Index CIBA : Chemical ındustry in Basel CKD : Chronic Kidney Disease CV : Cardiovascular Disease DBD : Donor after Brain Death DCD : Donor after Cardiac Death DHCA : Deep hypothermic circulatory arrest DNA : Deoxyribose Nucleic Acid DPD : Domino - Paired Donation EDTA-ERA : European Dialysis and Transplant Association-European Renal Assoc. ESRD : End Stage Renal Disease GDP : Gross Domestic Produce GFD : Glomerular Filtration Rate HD : Hemodialysis HLA-DR : Human Leukocyte Antigen - antigen D Related HNA (HAN) : Health Notification Application (SUT) IBPS : Incentive Based Procurement Systems ICU : Intensive Care Unit IRODat : International Registry in Organ Donation and Transplantation KDIGO : Kidney Definition Improving Global Outcomes KDOQI : Kidney Disease Outcomes Quality Initiative KPD : Kidney Paired Donation MDAT : Mobile Donor Action Team MESOT : Middle East Society of Organ Transplantation NATCO : North Ame4rican Transplant Coordinators Organization NCC : National Coordination Center NEAD Chain : Non-simultaneous Extended Altruistic Donor Chain NGOs : Non-Governmental Organizations NOTA : National Organ Transplantation Act NPV : Net Present Value OECD : Organization for Economic Co-operation and Development xiv

OPOs : Organ Procurement Organizations OPTN : Organ Procurement and Transplant Network PD : Peritoneal Dialysis PKE : Pairwise Kidney Exchange pmp : per million people PPP : Purchasing Power Parity QALY : Quality Adjusted Life Years RCC : Regional Coordination Center SCIE : Science Citation Index Expanded SEROPF : South-Eastern Regional Organ Procurement Foundation SEROPP : South-Eastern Regional Organ Procurement Program TRY : Turkish Lira TNA : Turkish Nephrology Association TNA : Turkish Notification Association TPC : Turkish Penal Code TPN : Turkish Penal Notification TSI : Turkish Statistical Institute Tx : Transplantation UCLA : University of California UNOS : United Network of Organ Sharing VSL : Value of a Statistical Life WHA : World Health Assembly WHO : World Health Organization

PART I: THEORY AND WORLD EXPERIENCE

1. INTRODUCTION

Within the last century, the world witnessed outstanding advancements in the field of surgery and organ transplantation with success ratios up to 80-90%. However there is a huge difference between the number of organs available for transplantation and those in need of transplantable organs. Rephrasing the preceding sentence within the context of economics, the fact is that there is a huge gap between the supply and demand of transplantable organs with shortage on the supply side. The only source of supply for transplantable organs is the human body. Among the transplantable organs, kidney comprises the major demand. There are systems regarding transplantation and they are based on donation around the world. For the last few decades the gap is growing drastically and the systems mentioned are insufficient to balance the supply and demand of transplantable organs and specifically within the scope of this thesis, the shortage of kidneys. There is no recent or a solid study about the costs and benefits of kidney transplantation in Turkey. This thesis primarily aims to calculate the costs of dialysis and/versus transplantation and to focus on the benefits of increasing the number in donations. This number of donations is further used in a sensitivity analysis of economic gains by increase in donations in section 11.1. Beyond ethical concerns, the economic dimension of compensated kidney donation is depicted. This compensation in concern is based on the loss (es) of the donor, not on the commodification of the kidney. A monetary incentive would be affected especially with the value of a statistical life (VSL). Another sensitivity analysis of the effect of monetary incentive by changing the VSL is given in section 12.3.

Among the many challenges during this study, data collection from related organizations and stakeholders such as hospitals, Social Security Institution and Ministry of Health

(Turkey) is a tough issue. All kind of applications for any formal and statistical data for this study were rejected and only one set of raw data was obtained from one single hospital after three and a half months of intense effort. The Social Security Institution responded seven months after the applications for data acquisition and rejected the request on the basis of privacy of personal information. These raw data must be compiled and made ready for proper calculation.

There is no methodological study about the variables of this study. There are many variables those could change the calculation, some of which are age, gender, social status and comorbidities before and after a kidney disease etc. The calculation is based on the costs of transplantation from a deceased and a living donor without any comorbidity under regular hospitalization.

The purpose of this study is to make a contribution to the health literature by calculating the costs and benefits of kidney transplantation. Although there is (a) system, there is also (a) system failure thus current system(s) is (are) insufficient in terms of reducing the prolonging waiting list(s). Therefore this thesis proposes an alternative system that would help increase kidney donations and transplantations. The proposed system would also heavily suppress the black market that abuses poor people.

Advancements and achievements in medicine and medical technology intend to prolong the life time of human beings. Following the invention of immunosuppressive drugs in late 1970s, success ratio in organ transplantation increased significantly which is considered as an ultimate realization of extending the life span. Today, availability of transplantation of various types of organs brings hope for patients. However the shortage in supply of transplantable organs, and especially of kidneys, is the principal problem and the difference mentioned at the very beginning of this Introduction keeps growing every day. The main sources for transplantable organs are donated organs: either living or deceased donations. After World Health Organization (WHO) banned selling and buying organs/organ trading (WHO: 1984), transplantable organs are only available through altruistic donation.

This thesis begins with the historical development of organ transplantation. Transplant surgery is mentioned and discussed in many historical sources (Howard et al.: 2012, Carrel: 1902) and the first successful organ transplantation was achieved by Yurii Voronoy

in 1936 (Voronoy: 1937). After the invention of immunosuppressants medical surgeons achieved to successfully transplant kidney from human to human. This success made possible the transplantation of other organs like liver, lung and tissue.

The increase in number of organ transplantations together with an emerging shortage of transplantable organs gave rise to ethical and moral concerns. Therefore, necessity and requirement brought about legal acts for allocation, grafting and donation of transplantable organs. Brief information regarding the development and history of the legal status in Turkey and in the world is given for convenience in this thesis.

Almost 70% of all transplanted organs are kidneys all around world (IRODat: 2014) therefore the study focuses specifically on kidney transplantation. Diagnosis of the kidney disease, symptoms and stages those end with transplantation are important to understand the shortage in kidneys therefore the definition of Chronic Kidney Disease (CKD) is given as the focal point.

Chapter 5 examines the donation systems in the world. These systems differ with respect to their objections so they need to be explained with their benefits. Each system has its own perspective and the governments enact these regimes according to these perspectives. These systems are classified into three main groups: opt-in system, opt-out system and monetary incentive. Each one of these systems has dimensions for living and deceased donation. Another system for allocating donated organs is pairwise kidney exchange and/or NEAD Chain. This system does not focus on increase-in-donation however makes allocation more effective.

Chapter 6 examines kidney allocation system with respect to its economic dimension(s). The determinants of supply and demand together with the effect of monetary incentive on supply and demand are examined.

Monetary incentive could be effective for increasing organ donation, especially in poor countries. Black-market for organs and transplant tourism is explained in Chapter 7. According to reports generated by WHO; almost 5 to 10 percent of kidney transplantations are performed by organ trafficking every year (Budiani-Sabeni and Delmonico: 2008). At this point it is crucial to understand the driving factors of illicit organ transplantation. These factors could be traced down to their root causes those might enable stopping the

abuse of people suffering under challenging conditions since organ traffickers take advantage of these conditions by offering these people a covenant to change their lives.

Legal regulations are the main factors for increasing (or decreasing) the donation rates and allocation of grafted organs. This thesis proposes a system for increasing the donation rates therefore the structure of legal regulations and amount of kidney transplantation and donation in Turkey should be known and hence these are discussed in the following sections.

Chapter 8 gives a brief documentation of legal regulations in Turkey and Chapter 9 compares the change in donation and transplantation in numbers from 1990’s to present. One of the primary pillars is the selection of the recipient and allocation of the grafted organ. The actual system in Turkey is examined in section 9.3 in light of the preceding discussion.

The primary objective of this thesis is to make a cost-benefit analysis of dialysis and kidney transplantation in Turkey. This requires the calculation of the costs of dialysis and transplantation. Government pays a standard amount for each dialysis session that is recalculated every year on the basis of annual inflation rate. However gathering reliable data for the costs of transplantation is almost impossible because of the restrictions of the Act about confidentiality of personal information. The data utilized in this study are obtained by special permission from Atatürk Education and Research Hospital. These data are the key component of the analysis. Having made the cost-benefit analysis of kidney transplantation, costs of kidney transplantation versus dialysis in Turkey is compared. In addition, similar analyses from different countries in academic literature are examined. A sensitivity analysis with variables of donation rates, waiting-list and number of transplantations is given in section 11.1.

One other primary pillar of alternative system proposed in this thesis is a monetary incentive. The factors affecting the amount of a monetary incentive and its (likely) effect on the number kidney donation is discussed in Chapter 12 with another sensitivity analysis. The amount payable is considered as a compensation of losses of donor but not as a price for a kidney. This could be perceived as the commodification of (a) kidney. In altruistic donation; recipient, surgeons, hospital and even the government (or insurance system) has a stake however the donor gets only moral relief which may not be enough to encourage

the potential donors to donate. At this point, the amount of a monetary incentive could be a motivator to encourage such potential donors.

Chapter 13 focuses on one pillar of this thesis which is the proposal of an alternative donation system. This proposal is divided into following three subtitles: opt-out regime, government monopsony and monetary incentive. The benefits and arguments in the academic literature of each subtitle are examined in section 13.2.

There are ongoing debates about all of the regimes and proposals. As the organ shortage increased in last few decades, the effect of monetary incentive is broadly discussed despite all its errors, transgressions and misdeeds. A unique example of where this system is applied is Iran that is (relatively) successful in terms of handling the waiting-list issue. This success draws the attention of alternative system researchers. Chapter 13 also takes into consideration the debate mentioned in the preceding paragraph. The data taken from Atatürk Education and Research Hospital are very detailed and are a bit complicated. The data set is given in Appendix 3 and can be obtained from the author.

2. HISTORICAL DEVELOPMENT OF ORGAN TRANSPLANTATION

The ancient history comprises myths and artworks giving reference to transplantation. Hindu texts dating back to 2500-3000 BC contain stories about grafting (Howard et al.: 2012, Carrel: 1902). Transplantation is also mentioned in Chinese legends. In one of these, Pien Chao transplants the heart of a man to change his spirit who he considers spiritually weak (Marino, Cirillo: 2014, p.2). The Bible also includes some stories mentioning transplantation. The story named “the miracle of the black leg” in Christianity is a valuable example for transplantation in historical and religious records together with its core argument that the leg transplanted was black conveys a universal message; religion is not restricted with races and color of the skin (Howard, Cornell: 2012). According to the story, the custodian of the church is crippled with an ulcerous leg. In his dream, two saints appear in his room holding medical instruments and they consult each other to replace his leg with that of an Ethiopian man that had died the day before1. In 1883, Theodor Kocher transplanted a thyroid tissue into a patient who suffered from radical thyroidectomy. For his study about transplantation he won the Nobel Prize in 1909. In the 18th century, John Hunter made some transplantation experiments on animals. On December 7th, 1905, Austrian physician Eduard Zirm performed transplantation to a human which was recorded as the first successful (cornea) transplantation from human to human (Armitage, Tullo and Larkin: 2006). Mathieu Jaboulay and his team including Carrel worked on an improved method of vascular suturing in Lyon (Carrel: 1902). Alexis Carrel transplanted a kidney from a dog in France (Carrel: 1905). When he moved to the U.S., aviator Charles Lindbergh and Dr. Carrel, recipient of the Nobel Prize in 1912 for Physiology and Medicine for his work in vascular surgery invented the Carrel-Lindbergh perfusion pump which led to the development of the heart-lung machine2 (Howard, Cornell: 2012). By the beginning of the 20th century successful transplantation of skin and cornea was already available. Dr. Harold Neuhof wrote his book in 1923, Transplantation of Tissues, about transplantation of skin, cornea, fascia, muscles, nerves, bones, teeth, blood vessels, ovaries, parathyroids, adrenal glands, testises and pancreases (Neuhof: 1923). In 1925, Dr. Serge Voronoff wrote the Rejuvenation by Grafting, about testicular transplantation to older men those with loss of libido or sexual dysfunction (Varonoff: 1925).

1http://www.theroot.com/miracle-of-the-black-leg-honorable-act-or-exploitation-1790874834 2 http://americanhistory.si.edu/collections/search/object/nmah_688713 6

The first kidney transplantation was performed by Russian doctor Yurii Voronoy in 1936 (Voronoy: 1937). Transplantation was performed from a deceased donor into the body of a young woman with a mismatch of blood-types (Hamilton: 1984, p. 289-294). Although the patient survived only for two days, this was the first successful transplantation recorded. The first modern kidney transplantation was performed in 1947 by David Hume from a deceased body into a young woman (Diethelm: 1990, p. 505-520). Between 1951 and 1953, Hume and his colleagues performed 9 transplants however it had not been possible to achieve a long-term survival for any of the recipients (De Vita MA: 1993, p. 113-129). In 1952, kidney transplantation was performed by a group of French doctors from a mother into his son. The recipient in this case survived only 22 days before the organ was rejected (Linden: 2009, p. 165-184). In 1954, the first successful transplantation was performed by Joseph E. Murray and his team from two identical twins after which the recipient lived 8 more years whereas the donor twin lived for 56 more years (Hakim and Papalois: 2003 p.92, Tinley: 2003). This successful surgery raised the question whether it was a must in order to perform transplantation from twins, since the use of immunosuppressives were not needed. If it had been considered that transplantation was possible only between twins most probably the need for immunosuppressives was never going to be realized.

The major problem that the physicians were facing was the fact that transplantation was not possible without the same DNA structure. Therefore, kidney transplantation had not been a treatment up until the development of immunosuppressive drugs. Experiments were made on animals based on cortical hormones; however the modest immunosuppressive effect of cortisone was achieved in early 1950s. In the late 1950s total body irradiation and allograft bone marrow rescue attempts were made in Paris, Boston and other institutes (Hamilton: 2008, p.5). In 1959, experiments about using 6-mercaptopurine on kidney transplant operations were made (Hakim and Papalois: 2003) which had success for immunosupprant use. In 1960 scientists started to use immunosuppresants on patients however the dosage presented a problem. 6-mercaptopurine was the ancestor of the main drug, azathioprine. The latter drug was more effective and useful than the other one. The combination of azathioprine and prednisone was making transplantation available. From 1958 to 1961, different variations of immunosupresives such as 6-mercaptopurine (6-MP), methotrexate and other anti-cancer drugs were used. David Hume, Roy Calne, Murray and

other surgeons tried to find and assess the proper formulation and dosage in clinics in London and Boston. Küss and colleagues succeeded on their studies regarding the survival of a non-related kidney patient (Küss et al.: 1962). This is known to be the first success of chemical immunosuppression.

12 patients were transplanted with azathioprine; except one, the others did not survive after the surgery (Murray et al.: 1960). In 1962, Dr. Murray performed the first successful kidney transplant from a deceased donor. The donor had several head injuries and transplantation was approved by the chairman (Howard et al.: 2012). This permission brought about the issue for an approval. Legal and ethical considerations begun almost at the same time with early successful operations. Moreover, Murray declared this problem as it first hashed out (Murray: 1976).

In 1963, Thomas Starzl performed the first liver transplantation and the same year James Hardy performed the first lung transplantation. The applicable combination of steroids, prednisolone and azathioprine was formulated (Starzl: 1978), survival rates had increased and an optimistic era had started by 1966 (Murray: 1976). Furthermore, the first successful pancreas transplantation was performed in 1966 by Richard Lilehei and again the first successful heart transplant was performed by Christian Barnard in 1967.

2.1. Definition of Brain Death

Until the first successful transplantation which was performed in Belgium with the approval of the chairman, asking for permission had not been something ever considered before. This successful surgery had been the precursor of the possibility of transplantation. But how was it going to be possible for surgeons to transplant other organs like lung, heart, cornea rather than liver and kidney based on the fact that if someone is dead, his/her heart wouldn’t beat and organs wouldn’t function, and thus not be available for transplantation.

The achievements between 1950s and mid-1960s faced physicians, ethicists, philosophers, government officials and religious leaders with the question on the definition of “death”

(Howard: 2012). The accepted traditional definition of “death” was the cessation of breathing and “irreversible3” circulation (Howard: 2001).

At this point, the definition of death becomes much more critical. As long as there are conflicts about the definition, some other arguments based on ethical and legal issues would eventually arise. Although there is a legal definition, there is also an argument going on. The current definition and classification regarding the distinction between dead and alive gives an opportunity to graft organs while they are functioning.

Wertheimer et al. were the first to characterize death in 1959 by defining the failure in nervous system that was treated by artificial respiration (Wertheimer: 1959). The term “beyond coma” that defined an irreversible state of coma and apnea was used by Mollaret and Goulon. This was the first attempt to define “brain death” however the issue of continuing heartbeat was still not resolved (Mollaret, Goulon: 1959). Advancements in biomedical technology gave raise to sophisticated intensive care unit (ICU) techniques and mechanical ventilators. This helped pave the way to the definition of brain death.

In 1968, Symposium on Transplantation was held in London with the attendance of physicians, lawyers and others concerned on ethical and legal issues of transplantation. An extensive description of brain death was given in this symposium for the first time (Machado: 2005). The Ad Hoc Committee gathered to define brain death in London in 1968. The very first problem was to determine the characteristics of a non-functioning brain (Beecher et al.: 1968). Accordingly, the following conditions had to be diagnosed for a brain-dead individual:

1. unreceptivity and unresponsivity 2. no movements of breathing 3. no reflexes 4. flat electroencephalogram

This was a great movement to stand the medical declaration on a legal ground. There are three major results to confirm brain death: a) coma and unresponsiveness, b) absence of

3 Irreversible means that breathing and circulation cannot be functioned again by ventilators or any other medical devices 9

brainstem reflexe,s c) apnea (Morris, Knechtle: 2014, p.:94)4. This declaration had been the pioneer of legal status.

The importance of the definition comes into prominence for the satisfaction of conditions under which organs can be grafted. After cardiac death, the majority of the transplantable organs stop functioning. On the other hand, as one individual is defined brain-dead, most of his/her non-vital organs would keep functioning; however the body depends on a life- support machine to keep those organs functioning. Increasing number of transplantation shows that there is a great demand on kidney (and other organs) and having the definition of death re-defined from “cadaveric” to “brain” resulted with a significant increase in the number of transplantable organs. Between 1997 and 2007, approximately 53,000 people on average died from traumatic brain injuries every year in the U.S. (Coronado et al.: 2011). These figures increase every year because of motorcycle and car accidents, suicides and various other reasons.

There are many examples about revival after “irreversible coma” and those who oppose this idea keep debating on these examples. Ethical arguments are based on “the right of unplugging the machine”, “human dignity”, “integrity of the human body” and other humanitarian concerns, however these issues are beyond the scope this thesis.

2.2. History of the Legal Status about Organ Donation

In 1968, the Ad Hoc Committee of Harvard Medicine School published a report to examine the Definition of Death. This was ground-breaking because this definition enabled surgeons to perform actually all types of transplantations. Sequentially various states and countries accepted this definition as a medical law. The same year, the Uniform Anatomical Gift Act stated that an 18 year-old person could donate his/her organs after his/her death. Finland was the first country that accept brain death and Kansas was the first state that legalized brain death in 1970 in the U.S.

The improvements in medical care, intensive care and immunosuppression were promising. Although the use of immunosuppressives had increased the success ratio in transplantation surgeries from deceased donors, they did not help realize the expected

4 For more information about the medical diagnosis of brain death and cardiac death see; Morris, Knechtle, Kidney Transplantation: Principles and Practice, 2014, page: 91-104 10

increase in survivals after transplantation. The problem was solved by a successful clinical application of HLA-DR (Ting, Morris: 1978).

Figure 1: Distribution of organ donation from brain death and cardiac death in the U.S. Source: Linden (2009)

Seeking for different methods for increasing the number of donations was raised intensely throughout 1970s. The United Kingdom was the first country that introduced the Kidney Donation Card in 1971. The American Bar Association established brain death as a legal and medical fact in 1975. In 1976, France initiated an opt-out policy that assumed everybody as a potential donor unless declared otherwise before death. The Uniform Determination of Death Act drafted in 1978, recognized brain death as a legal concept and was approved at the National Conference of Commissioners on Uniform State Laws.

The United States legalized brain death upon the approval of the Uniform Determination of Death Act through a landmark report issued by the Presidential Commission in 1981 (Howard: 2001). It defined death as an irreversible cessation of circulatory and respiratory functions or cessation of all functions of the entire brain, including brain stem. “Guidelines for Determination of Death” was published by this committee and now it is effective in all states. It is still being periodically revised by the American Academy of Neurology.

The act about brain death granted surgeons the required legal ease for transplantation however declaration of “legal death” was another issue. In some states, examination and

declaration of only one physician was deemed sufficient to confirm brain death whereas in some others more than one physician was required.

The clinical and medical innovations enabled better techniques for preservation. Total body hypothermia of the living kidney donor during surgery was something already achieved in the early 1960s. Initial attempts for preserving the kidney up to 48 hours5 were unsuccessful. Later on, scientists begun to apply hypothermic methods on human kidneys (Starzl: 1963). It became possible to preserve and transport the organs of a dead body in a short time and for short distances. Owing to improved techniques in time, preservation and transportation for far more distances became available. Until James Southard and Folkert Berzer in the University of Wisconsin in 1980s developed a proper formula, various flush solutions6 were tried. This and such medical and pharmaceutical achievements made far more things possible; transplantation of different organs from a dead body for more than one recipient at more than one single facility was possible, however there had raised far more responsibilities imposed on the stakeholders.

Developments in preservation techniques gave rise to the establishment of many organ banks those functioned almost in the form of organ procurement agencies. The New England Organ Bank founded in early 1970s served for more than 10 transplant programs.

At the early stages of transplantation era, an organization for organ allocation was not needed. Almost all of the transplanted organs were form living donors. Transplant centers were at a limited number and donors and patients had to be at the same center. However, two important achievements those were advancements in preservation and new advancements in tissue typing (Williams et al.: 2004), made allocation organization necessary together with the principles of the legalization of allocation. In addition, increase in the number of transplantations, demand and donations forced regulatory authorities for a system to organize procurement policies. Definition of “brain death” was the first step among the early attempts. However there were still other issues those had to be clarified:

. Grafting and preservation of organs donated, . Transportation of grafts into proper distances (if needed), . Classification of patients according to their needs and urgency,

5 Ex vivo sanginous and asangunious artificial pulsatile perfusion techniques. 6 Collins solution, Euro-Collins solution and University of Wisconsin solution were some of these flush solutions. 12

. Allocation of donations on a fair basis.

The innovations in matching the donor and preservation of the organ up to 12 hours made formal regional organ sharing programs necessary (Williams et al.: 2004). The Los Angeles Transplant Society and the Regional Organ Procurement Agency of Southern California were established in 1967 those were the first establishments recorded for kidney distribution (Howard et al.: 2012, p. 11). In 1969 an organ sharing program, South-Eastern Regional Organ Procurement Program (SEROPP), was founded under the leadership of David Hume and Bernard Amos with the participation of 8 hospitals in 4 states (Teresaki et al.: 1971). Dr. Paul Terasaki at UCLA expanded this organization to 61 West and Midwest transplant centers. SEROPP became an independent non-profit organization called South-Eastern Organ Procurement Foundation (SEOPF) incorporated with an online system for matching and sharing organs for transplantation (Ferree, Stearns: 1996). In 1977, this system gave rise to the United Network for Organ Sharing (UNOS), a computer system for registering potential patients, donors and sharing kidneys of non-SEOPF and SEOPF centers (Pierce: 1996, pp. 1-5). This kind of a distribution system enabled a larger sharing network, ease of transportation and decreased costs. This computer system was transformed into establishing a 1-year pilot Kidney Center program that was funded by American Kidney Fund. The success of this pilot program led to a country-wide organization which was funded by the Health Care Financing Administration in 1984 (SEOPF Newsletter: 1994, pp. 5-9). By contract with The Health Resources Services Administration of U.S. Department of Health and Human Services, the UNOS program started to serve as the Organ Procurement and Transplant Network (OPTN). Next year, UNOS separated from SEOPF with its computer facilities, personnel and other units (Pierce: 1996).

As computer technology became more sophisticated, the UNOS program evolved into the Organization for Transplant Professionals (NATCO) funded by Richard King Mellon Foundation that enabled a 24-hour alert system. Payment was an important issue within this process. Since transplantations were experimental, all the costs were financed by hospitals (Prottas: 1989). Kidney transplantations were expensive operations. Non-profit organizations for transplantation program were established which are considered the origins of independent Organ Procurement Organizations (OPOs). An amendment in the Social Security Act in 1971, guaranteed Medicare for recovery costs (Howard et al.: 2012).

Before the End Stage Renal Disease Act came into force, patients had to pay the costs, however most of them couldn’t afford the dialysis, transplantation and organ procurement. Besides, many insurance policies were not covering the costs (Howard: 2012). The Social Security Act which was repeatedly amended in three decades extended the coverage and enabled payment of transplantation and/or dialysis costs by the help of social security systems.

Figure 2: Major legislative and regulatory landmarks of organ donation and transplantation (U.S.) Source: Howard et al. (2012)

Table 1: Major legislative and regulatory landmarks and other requirements affecting organ procurement organizations (OPOs). Source: Howard et al. (2012)

1. 1935 Social Security Act: federal forerunner of the acceptance of public responsibility for the aged, needy, deprived and handicapped. 2. 1965 Medical/Medicare Laws, titles XVIII and XIX of the Social Security Act. 3. 1968 Uniform Anatomical Gift Act: legalizes organ and tissue donation for transplantation. Gave adults the right to donate their bodies or organs without subsequent veto by others. Passed by the Conference of Commissioners on Uniform State Laws as a suggestion for individual states. 4. 1968 Report of the Ad Hoc Committee of the Harvard Medical School to examine the definition of the brain death: defines brain death. 5. 1969 Kidney disease and its control placed under the aegis of the Public Health Services of the Department of Health, Education and Welfare (HEW) – Forerunner of the Department of Health and Human Services (DHHS). The Public Health Service launches kidney transplantation program to maintain computerized donor/recipient matching program. Contract with University of California, Los Angeles involved 7 deceased kidney procurement contracts. 6. 1970 Kansas is the first state to pass the brain death legislation. 7. 1971 Uniform Anatomic Gift Act: establishes legality to donor cards. 8. 1971 All states had adopted the Uniform Anatomic Gift Act. 9. 1972 End Stage Renal Disease Act (PL 92-603): Social Security Amendment – provides Medicare coverage for kidney failure, including dialysis and kidney transplantation, and pays for organ procurement. 10. 1973 (38 Federal Register p. 17, 210): interim regulation for the financing organ acquisition. 11. 1976 (41 Federal Register p. 22, 502): final rules for the financing of organ acquisition. 12. 1976 Centers for Disease Control and Prevention (CDC) initiated analytic effort to improve the performance of the organ procurement system—sought to apply methods of epidemiology to organ donation and acquisition. Tried pilot programs in Atlanta, Georgia, and Kansas City, Missouri. 13. 1976 Uniform Death Act: National Conference of Commissioners on Uniform State Laws. 14. 1978 President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research: expands studies of brain death and informed consent. 15. 1980 President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research drafts the United States Uniform Determination of Death Act. 16. 1981 Uniform Determination of Death Act approved. Common law basis for determining death. Defines death as irreversible cessation of circulatory and respiratory functions, irreversible cessation of all brain functions including the brain stem. 17. 1984 National Organ Transplant Act (NOTA) (Public Law 98-507). OPOs must be members of the Organ Procurement and Transplant Network to receive payment from Medicare. Established the Organ Procurement and Transplant Network, prohibited buying and selling of organs, established the Task Force on Organ Transplantation.

Table 1 continued 18. 1986 Task Force on Organ Transplantation report (task force was created by NOTA): recommended health professionals identify prospective donors and notify OPOs, hospitals adopt routine inquiry/request protocols, that the Joint Commission on Accreditation of Health Care Organizations (JCAHO) adopt a standard that required affiliation with an OPO as well as policies and procedures to identify prospective donors and give donation opportunity to the next of kin, that the Defense Department and Veterans Administration require their hospitals to adopt required request protocols, that the Health Care Financing Administration (HCFA) require hospitals to have routine request protocols as a condition of participation. It also recommended that OPOs and procurement specialists be certified and that only a single OPO be certified in “any standard metropolitan area”; “that each donated organ should be considered a national resource and be used for the public good”; and a governance structure for independent OPOs, which was incorporated into federal guidelines as a condition for receiving a supporting federal grant. 19. 1986 Omnibus Budget Reconciliation Act (Public Law 99-509, Section 9318) Required Request legislation: families of potential deceased donors had to be asked whether they wanted to donate their loved one’s organs for transplantation. Gave the HCFA the authority to certify OPOs. 20. 1987 Revision of the Uniform Anatomical Gift Act: prioritized decedent’s wishes, prohibited organ sales, required hospitals to institute a required request policy. 21. 1987 Omnibus Budget Reconciliation Act (Public Law 100-203): further defined laws governing OPOs. 22. 1987 Uniform Anatomic Gift Act prioritized descendant’s wishes for donation over family wishes, requires hospitals to inquire about organ donation. 23. 1988 DHHS, HCFA, Medicare and Medicaid programs approved regulations implementing the 1986 Omnibus Budget Reconciliation Act affecting OPOs and other organ procurement protocols, (42 CFR Parts 405, 413, 441, 482, 485, and 498 Fed Register 1 March 198; 53 (40): 6526-6551). 24. 1988 JCAHO, now renamed The Joint Commission, requires hospitals to identify potential donors and refer them for organ procurement. 25. 1988 Transplant Amendments (Title IV of Public Law 100-607): further defined OPO oversight. 26. 1990 Transplant Amendments (Public Law 101-616)–further defined OPO oversight. Further defined HCFA’s authority to certify OPOs. 27. 1993 Public Health Service Act (42 U.S.C. section 264, is the authority for the Food and Drug Administration’s Interim Rule for Human Tissue Intended for Transplantation. (Federal Register 14 December 1994; 58 (238):65514). 28. 1996 Organ Donation Insert Card Act, authorizes mailing information about organ and tissue donation with income tax refunds. 29. 1998 National Conditions of Participation (DHHS). 30. 1998 Health Omnibus Programs Extension–OPOs required to obtain 50 actual donors per year, requires OPOs to test donors to avoid spreading infection. 31. 1999 DHHS issues “Final Rule” for Organ Procurement and Transplantation.

Table 1 continued 32. 2003 Health Research and Services Administration announces the beginning of the Collaborative efforts to increase the number of organ transplants and reduce deaths on the waiting list. 33. 2003 Health Research and Services Administration announces the beginning of the Collaborative efforts to increase the number of organ transplants and reduce deaths on the waiting list. 34. 2006 Uniform Anatomical Gift Act–further revision in light of new federal regulations. 35. 2007 DHHS–CMS–Final Rule for Transplant Centers. 36. 2009 Uniform Anatomical Gift Act–addresses gift of the donor, first person consent, what to do when there is no next of kin.

2.3. History of Organ Transplantation in Turkey

The modern transplantation history dates back to early 1960s in Turkey. Despite various unsuccessful attempts, first successful transplantation was performed in 1962, after the invention of immunosuppresives. Transplantations in Turkey began very short after the first transplantation surgeries abroad. In 1969, there were two unsuccessful attempts of heart transplantation in Ankara and in İstanbul. M. Haberal and his team made experimental studies on animals in Ankara in 1972. First experimental liver transplantation surgery was performed on pigs and dogs in early 1970s (Haberal et al.: 1972). First living- related kidney transplantation was also performed by this team at Hacettepe University in 1975. Another milestone for Turkey was the deceased donor kidney transplantation which was performed in 1978 (Haberal et al.: 1988). This kind of a kidney donation was legally restricted therefore the kidney was supplied through Eurotransplant (Karakayalı and Haberal: 2005). Legal loopholes are a combination of legal, ethical, medial, social, psychological, technological, economic and religious aspects of transplantation and they need to be systemized by law. These perspectives are examined in the following chapters of this thesis.

Legalization issues were the main problem for transplantation. The supply of organ has two sources: either dead or living donors. At the beginning of experimental transplantation surgeries, supply of organs from deceased donors were “cardiac death” donors since the accepted definition of “death” was cardiac death. After the recognition of definition of brain death, a broader capability was enabled for grafting organs from deceased donors. As transplant surgeries advanced, need for regulations in organ transplantation arose. In 1979, the 2238 numbered law about “organ and tissue recovery, preservation, inoculation and

transplantation” was enacted. This law was basically about recovery, storage, grafting and transplantation of organs and tissues and had 4 main chapters; general provisions, organ recovery from a living donor, organ recovery from a deceased donor and penalties (Karakayalı and Haberal: 2005). The first local renal transplantation was performed the same year in July (Haberal, Öner et al.: 1984). Religious concerns were an important issue in order to persuade citizens to become organ donors. After 2238 numbered law was enacted, as a result of Haberal’s initiatives, the Supreme Council of the Directorate of Religious Affairs issued a fatwa in 1980 stating that there are no constraints and restrictions regarding organ donation and transplantation (Moray et al.: 2014).

Table 2: Some articles from Turkish Law on harvesting, storage, grafting and transplantation of organs and tissue. Source: Haberal and Karaali (2005)

Turkish Transplantation Law #2238, on the harvesting, storage, grafting, and transplantation of organs and tissue (June 3rd, 1979) . The buying and selling of organs and tissues for a monetary sum or other gain is forbidden. . Harvesting organs and tissues from persons under the age of 18 or those who are not of sound mind is forbidden. . In connection with enforcement of this law, the cause of medical death is established unanimously by a committee of four physicians consisting of one cardiologist, one neurologist, one neurosurgeon and one anesthesiologist by applying the rules, methods and practices that the level of science has reached in the country. . The physician who will perform the transplant surgery may not be a member of the group that pronounced the donor as dead. Turkish Transplantation Law #2594 (January 21st, 1982) . In the case of the aforesaid persons, where next of kin do not exist or can be located, and the termination of life has taken place as a result of accident or natural death, provided that the reason for the death is not in any way related to the reason for the suitable organs and tissues can be transplanted into persons whose lives depend on this procedure without permission from the next of kin.

In 1980, The Turkish Organ Transplantation and Burn Treatment Foundation was established and the first organ donation cards were printed. In 1982, new articles regarding the issue came into force with the enactment of the 2594 numbered law. In 1987 Middle East Society of Organ Transplantation (MESOT) was established with the contribution of eight Middle Eastern countries. After in 1990, Turkish Organ Transplantation Society was founded and was later associated to MESOT. In addition to organizing biennial congresses,

MESOT is publishing its official journal “Experimental and Clinical Transplantation Journal” since 2003 (Akbulut, Yılmaz: 2014).

In 1988, the first liver transplantation from a deceased person was performed by Haberal and his team (Haberal et al.: 1992). History of Turkish liver transplantation is divided into three stages by Dr. Sezai Yılmaz: initial stage (1988-1996), development stage (1997- 2001), rise and spread stage (2002-2014) (Akbulut and Yılmaz: 2014). National organ sharing program was initiated in 1989 and National Coordination Center was established in 2001 by Ministry of Health which involves 9 coordination centers on the basis of geographic location, population, allocation and transplantation demand. The “Turkish Organ and Tissue Information System” was initiated to coordinate and distribute organs properly in a fair manner among the recipients and transplantation centers. Ministry of Health initiated “the national organ and tissue transplantation coordination system in 2011 via a directive. Another milestone was the first international paired kidney transplantation that was performed in May, 2013 (Tuncer et al.: 2015).

Today, organ transplantation is an effective, professional and expanding organization in Turkey under the leadership of Ministry of Health. Coordination Centers are well- organized and almost all potential donors are carefully considered with computer based systems. Although donation rates are insufficient (donation rates will be examined in Chapter 4), Turkey is the leading country in the world in terms of living kidney donation rates.

3. WHAT IS CHRONIC KIDNEY DISEASE (CKD)?

Tissues, bones, eyes, lungs, liver and even heart are transplantable organs however all of them require deceased donors with the exception of kidney and liver. Especially kidney transplantations yield very effective results. Most of the transplantation surgeries are kidney transplantations. Besides, operations are relatively easier when compared to transplantation of other organs with a minimum damage to donor which is acceptable for any potential donor. Making a decision regarding the urgency of a recipient’s need for transplantation is a delicate issue. Patients move towards the end-stage renal disease (ESRD) in phases, thus recognition of the definition of CKD is crucial.

The functions of kidney are cleaning the blood from toxic matters, balancing liquid equilibrium and blood pressure and secreting hormones etc. An agreed upon definition of kidney disease helps physicians make diagnoses. KDIGO (Kidney Disease Improving Global Outcomes)7 is an independent charity organization which is managed by the National Kidney Foundation in the U.S. KDIGO organizes conferences all over the world with the attendance of well-known nephrologists and publishes reports and guidelines which include every aspect of CKD. Besides, KDIGO definition on CKD is accepted globally. The first of International Controversies Conference was held in Amsterdam about the “Definition and Classification of Chronic Kidney Disease” in November 2004. The goals of this conference were to 1) provide a clear understanding to both the nephrology and non-nephrology communities of the evidence base for the definition and classification recommended by Kidney Disease Outcomes Quality Initiative (KDOQI)8, (2) develop global consensus for the adoption of a simple definition and classification system, and (3) identify a collaborative research agenda and plan that would improve the evidence base and facilitate implementation of the definition and classification of CKD9.

7 www.kdigo.org KDIGO is a global organization developing and implementing evidence based clinical practice guidelines in kidney disease. 8 K/DOQI is an initiative held in the first KDIGO conference. 9 http://kdigo.org/home/conferences/definition-and-classification-of-chronic-kidney-disease-in-adults- worldwide-2004/ 20

Topics were definition and classification of CKD, Glomerular Filtration Rate (GFR) and assessment/measurement of albuminuria and proteinuria which are important to classify the level of kidney disease. (Levey, Eckardt et al.:2005).

CKD is classified either by a reduced GFR or kidney damage indicators like proteinuria, hematuria or biopsy etc. Reduced GFR must be < 60 mL/min/1.73 m2. At least three samples must be taken in a three month-period and these samples have to be positive for protein or albumin.

Table 3: Five stages of chronic kidney disease as defined by KDOQI guidelinesa Source: Brosnahan, Fraer (2010), Weiner ( 2007)

CKD Stage GFR Description Action Plan Kidney damage, Diagnosis, treat comorbidities, Stage 1 ≥ 90 mL/min/1.73 m2 Normal GFR slow progression Kidney damage, mild Stage 2 60 – 89 mL/min/1.73 m2 Assess progression decreased GFR Stage 3 30 – 59 mL/min/1.73 m2 Moderate CKD Evaluate and treat complications Prepare for kidney replacement Stage 4 15 – 29 mL/min/1.73 m2 Severe CKD therapy Stage 5 < 15 mL/min/1.73 m2 Kidney Failure Kidney replacement therapy aGFR, glomerular filtration rate; KDOQI, kidney disease outcomes quality initiative

Another criterion for diagnosing the disease is about albuminuria is as follows:

Table 4: Albuminuria categories of CKD

Albuminuria categories in CKD ACR (approximate equivalent) AER Category (mg/mmol) (mg/g) Terms (mg/24 hours) A1 < 30 < 3 < 30 Normal to mildly increased A2 30 – 300 3 – 30 30 – 300 Moderately increased* A3 >300 >30 >300 Severely increased**

Abbreviations: AER, albumin excretion rate; ACR, albumin-to-creatinine ratio *Relative to young adult level. ** Including nephrotic syndrome (albumin excretion usually > 2200 mg/24 hours [ACR > 220 mg/g; > 220 mg/mmol]). (Levin et al.: 2013)

There are some other important complications that influence the management of patients and treatments (Said et al.: 2015):

a. Volume overload b. Metabolic acidosis c. Hypertension d. Anemia e. Mineral and bone disorders f. Uremia g. Dyslipidemia h. Infection

This thesis focuses on the economic perspectives of kidney disease, therefore complications and other related issues will not be discussed further.

3.1. Initial Symptoms of CKD

The prevalence of CKD is estimated from national surveys and health statistics (Brosnahan and Fraer: 2010). The results are classified and published by some researchers and initiatives such as K/DOQI. Coresh et al., surveyed the U.S. data between 1994 and 2004 and reached that obesity, diabetes, hypertension and aging are among the responsible factors increasing the prevalence of CKD (Coresh et al.: 2007). Similar results apply for researches from various other countries. Prevalence rate of CKD in people older than 64 is 13% in Beijing (Zhang et al.: 2008), 16% in Australia (Chadban et al.: 2003) and 23% to 36% in U.S. (Zhang and Rothenbacher: 2008).

CKD can occur at any age, however the people in the following categories have a higher risk of CKD (Brosnahan, Fraer: 2010):

. Diabetes type 1 and 2 . Hypertension . Obesity . Senescence (older age) . Hyperlipidemia . Family history of ESRD . Cardiovascular disease

Progressive kidney disease has some cardiovascular (CV) co-morbidities and mortalities in which most of the death-resulted CV diseases are caused by ESRD (Astor et al.: 2008). American Heart Association states that CKD patients are ranked in the high risk categories for CV events (Sarnak et al.: 2003). Traditional risk factors are classified by the Framingham Heart Study10.

Figure 3: Cardiovascular disease in CKD

3.2. Diagnosis of CKD

The main objective for diagnostic studies of CKD is on the limits of GFR. There are some other diagnostic tests for CKD patients such as urinalysis, quantification of proteinuria, renal ultrasound. There are additional diagnostic tests on the following clinical situations:

. Serologies for autoimmune diseases . Serologies for chronic infections (Hepatitis B, C, HIV etc.) . Serum and urine protein electrophoresis and immunofixation . Blood and urine cultures . Imaging studies for malignancy . Kidney biopsy

10 The Framingham Heart Study is to identify the common factors and characteristics of Cardio Vascular Disease over a long period in a large group of observations. For more information please visit https://www.framinghamheartstudy.org/ 23

The information contained up until this paragraph aims to provide a brief history on the development of transplantation together with a comprehensive understanding of the diagnosis of kidney disease. However the core argument of this thesis is the identification of the economic dimension of transplantation, which requires a thorough understanding and recognition of the disease. The following chapters will concentrate on the core argument and examine different dimensions of transplantation.

4. SUPPLY AND DEMAND OF KIDNEY AROUND THE WORLD

The transplantation of organs has been a revolution for many incurable diseases. After the availability of transplantation, some critical diseases related to lung, liver and kidney become treatable and furthermore, curable. In the meantime, techniques of transplantation advanced and complications those occurred at the early stages were solved. One of the most serious problems, mismatch on blood and tissues, was eliminated by use of immunosuppressive. There has been a significant increase on renal graft survivals from deceased and living donors after medical and surgical inventions and improvements (Hariharan et al.: 2000).

Invention of immunosuppressive became the light of hope for patients in concern. In this context, kidney disease is of different importance. In most other diseases the patients generally don’t have much time for treatment and they need be interfered as soon as possible while CKD patients have a considerably longer time since a CKD patient could survive almost 13-21 years with this disease (Hariharan: 2001). This means that, the patient has 13-21 years of time for proper kidney transplantation. In this time period, if s/he could find an organ s/he would be cured. At this point, a very major problem comes up into the picture: kidney shortage, in other words; not every patient is having an opportunity to find a proper kidney.

Kidney transplantation could be performed either from a deceased or a living person. Physicians have enough time to prepare and make examinations on both patients and living donors but from deceased donors the case if different and time matters; that is in most cases there is not enough time for preparation and elimination of risks, especially that of chronic rejection. These risks can be immunologic or non-immunologic factors in origin and need to be eliminated.

Table 5: Risk factors for chronic rejection Source: Hariharan (2011)

Risk factors for Chronic Rejection Immunologic risk factors Non-immunologic risk factors . HLA mismatch . Race, age and sex of recipient . Suboptimal immunosuppression . Donor status . Repeat transplantation . Length of dialysis . Elevated panel reactive antibody . Hypertriglyceridemia . Acute rejection . Hypertension Multiple acuter episodes . CMV (cytomegalovirus) infection Late (>1 year) episodes More severe episodes

A kidney from a deceased donor can be transported by cold ischemia up to72 hours at most, although there are cases (like M. Haberal, who did the first renal transplantation in Turkey) over 100 hours (Karakayalı and Haberal: 2000, p. 2906). However, cold ischemia more than 24 hours is always a risk factor of acute rejection (KDIGO Report: 2009, p. 8).

Owing to the fact that there is a great shortage in transplantable kidneys, each and every kidney donation becomes such a precious gift of life which requires careful and intense follow-up. Therefore, there are some governmental and non-governmental organizations established for this purpose. Almost every country has its own tracking system for their patients and donors, which is necessary for proper allocation of donations; however shortage of transplantable organs forces some desperate patients to look for hope in the black market.

International Registry in Organ Donation and Transplantation (IRODaT) is among some very important nephrologist organizations which publish data on annual, semi-annual, and quarterly basis. IRODaT registry reports are considered the most reliable sources of information in its field because of the universal participation, official reporters, transparency and availability. The statistics published come from official reporters who are members of National Transplant Organizations and Ministries of Health11. These reports include information about transplantation that is classified with respect to:

11 IRODaT is a non-governmental organization and publishes registries every year. For member list and reports visit www.irodat.org 26

. Worldwide actual deceased donors (pmp) . Worldwide living organ donors (pmp) . Worldwide actual donors after cardiac death (pmp) . Europe actual deceased organ donors (pmp) . Europe living organ donors (pmp) . America actual deceased organ donors (pmp) . America living organ donors (pmp) . Asia-Oceania actual deceased organ donors (pmp) . Asia-Oceania living organ donors (pmp) . Africa-Middle East actual deceased donors (pmp) . Africa-Middle east living organ donors (pmp) . Worldwide kidney transplant from deceased donors (pmp) . Worldwide kidney transplant from living donors (pmp) . Worldwide liver transplant from deceased donors (pmp) . Worldwide liver transplant from living donors (pmp) . Worldwide heart transplant (pmp) . Worldwide lung transplant (pmp) . Worldwide pancreas transplant (pmp)

The last annual report was published in 2014 and includes data from 80 countries. According to this report, leading countries from deceased donors are Spain (48.2 pmp), Austria (44.1 pmp), Croatia (43.2 pmp) and Belgium (43 pmp) and the ranking is more or less the same for every year.

Table 6: Kidney transplant from deceased donors 2014 (Source: IRODat Registry 2015)

Country Donation Rates (pmp) Country Donation Rates (pmp) Spain 48.2 Kuwait 13.7 Austria 44.1 Romania 13.6 Croatia 43.2 Colombia 13.5 Belgium 43 Cuba 13 France 42.1 Chile 11.9 Czech Rep. 41.5 Israel 10 Finland 41.1 Panama 9.7 Norway 40.2 Hong Kong 8.8 Portugal 38.2 Turkey 8.3 USA 38.1 Greece 8 Uruguay 37.9 Trinidad &Tob. 7.7 Malta 35.7 Costa Rica 7.6 Hungary 34.5 Cyprus 7.5 UK 32.8 Luxembourg 7.3 Sweden 29.8 Bulgaria 6.3 Poland 28.4 Mexico 6 Netherlands 27.9 Russia 5.7 Belarus 27.9 Macedonia 5.7 Latvia 27.4 Ecuador 5.1 Australia 27.1 Saudi Arabia 4.2 Slovenia 26.7 Dom. Rep. 4.1 Italy 26 Peru 3.9 Denmark 24.2 Venezuela 3.4 Ireland 24 Moldova 2.3 Estonia 23.6 Lebanon 2.2 Switzerland 22.7 Paraguay 2 Brazil 22.3 Bosnia Her. 1.8 Argentina 22.2 Montenegro 1.7 Slovak Rep. 20 Bolivia 1.6 Lithuania 19.7 Malaysia 1.3 Germany 18.6 Guatemala 1 South Korea 16.3 Ukraine 0.3 New Zealand 14.7 Vietnam 0.1 Iran 14.3 Algeria 0.02

Except Russia and Japan which are ranked in the bottom of the list, leading countries in general are the developed countries. Countries with lowest ranking are generally those countries known to be Muslim (data from most of the Muslim countries is not available,

the list contains data from a limited number of Muslim countries) which in turn brings about the fact that religious reasons and (poor) donation systems are the major effects in these low rankings.

Another source of supply is living donors. Since only transplantable organs from living donors are kidneys and parts of livers, living donor rates comprise additional significance.

Table 7: Kidney transplant from living donors 2014 (Source: IRODat Registry 2015)

Country Donation Rates (pmp) Country Donation Rates (pmp) Costa Rica 41 Czech Rep. 5.9 Netherlands 31.7 UAE 5.5 Turkey 30.6 Portugal 4.9 Cyprus 28.5 Hungary 4.7 Iceland 26.7 Lithuania 4.3 South Korea 20.2 Italy 4.2 Kuwait 19.3 Algeria 4.2 Denmark 19.2 Dom. Rep. 3.9 Lebanon 18 Greece 3.8 USA 17.2 Sudan 3.7 UK 17.1 Bosnia and Her. 3.7 Saudi Arabia 16.5 Uruguay 3.6 Israel 16.5 Latvia 3.5 New Zealand 16 Chile 3.3 Sweden 15.6 Armenia 3 Iran 15.3 Vietnam 2.8 Mexico 15 Slovak Rep. 2.7 Switzerland 14.8 Finland 2.7 Macedonia 13.8 Ukraine 2.6 Norway 13.3 Panama 2.6 Montenegro 13.3 Cuba 2.5 Malta 12 Croatia 2.5 Australia 11.4 Colombia 2.5 Azerbaijan 10 Belarus 2.44 Argentina 8.9 Hong Kong 2.2 Austria 8.3 Romania 1.8 Syria 8 Bulgaria 1.7 France 8 Poland 1.4 Trinidad & Tob. 7.7 Russia 1.3 Germany 7.6 Ecuador 1.3 Brazil 7.3 Malaysia 1 Bolivia 7.3 Estonia 0.8

Table 7 Continued

Guatemala 6.5 Paraguay 0.7 Belgium 6.1 Moldova 0.6 Georgia 6 Peru 0.4

When it comes to living donor ranking, the picture in leading countries is different. According to reports by IRODAT, Costa Rica has the highest ratio in living organ donations with 41 pmp, followed by Netherlands (31,7 pmp) and Turkey (30,6 pmp) in 2014. Since the majority of transplantations are kidney transplantations, this ratio affects the organ donations. Organ donation ratio differs slightly from kidney donation ratios because of the variety of transplantable organs especially from deceased donors.

Table 8: Worldwide actual deceased organ donors 2014

(Source: IRODat Registry 2015)

Country Donation rates (pmp) Country Donation rates (pmp) Spain 35.9 South Korea 9 Croatia 35.1 Iran 8.4 Malta 28.6 Kuwait 8 Portugal 27.7 Israel 7.7 USA 27.7 Luxembourg 7.3 Belgium 26.8 Colombia 7.3 Austria 25.5 Panama 7.2 France 25.3 Romania 6.9 Czech Rep. 24.4 Chile 6.9 Italy 23.1 Cyprus 6.5 Slovenia 22.8 Turkey 5.4 Norway 22.6 Hong Kong 5.4 Finland 22.1 Bulgaria 5.4 Uruguay 20.7 Macedonia 4.8 UK 20.4 Greece 4.5 Hungary 20.1 Trinidad & Tob. 3.8 Belarus 17.5 Costa Rica 3.8 Sweden 17.1 Saudi Arabia 3.4 Canada 16.5 Mexico 3.4 Netherlands 16.1 Russia 3.2 Australia 16.1 Moldova 3.1 Poland 15.4 Ecuador 3.1 Latvia 15.3 Dom. Rep. 2.96 Estonia 15.2 Thailand 2.8

Table 8 Continued

Brazil 14.2 Peru 2.4 Switzerland 14.1 Lebanon 2 Denmark 13.9 Venezuela 1.7 Ireland 13.8 Paraguay 1.3 Argentina 13 China 1.2 Montenegro 11.7 Bosnia 1.1 Slovak Rep. 11.6 Bolivia 0.8 Cuba 11.1 Malaysia 0.7 Germany 10.7 Guatemala 0.5 Lithuania 10.3 India 0.3 New Zealand 10.2 Vietnam 0.2 Iceland 9.2 Algeria 0.02

Leading countries for actual deceased organs around the world are more or less the same with the leading deceased kidney donation countries in these statistics. This is an expected result because of the donation systems of the countries. The outlier in this case is Spain which applies opt-out regime for organ donation. Ranking is far beyond the expectations for living donation when it is compared with the deceased donation rates.

Table 9: Worldwide living organ donors 2014 (Source: IRODat Registry 2015)

Country Donation rates (pmp) Country Donation rates (pmp) Turkey 42.5 Georgia 6.4 Costa Rica 41 Portugal 6 South Korea 37.5 Hong Kong 5.9 Netherlands 32.1 Czech Rep. 5.9 Cyprus 28.5 UAE 5.5 Iceland 24.6 Hungary 4.6 Saudi Arabia 20.8 Lithuania 4.3 Kuwait 19.3 Italy 4.2 Denmark 19.2 Algeria 4.2 USA 18.3 Uruguay 3.9 Israel 18.2 Dom. Rep. 3.9 Lebanon 18 Greece 3.8 UK 17.6 Sudan 3.7 New Zealand 16.9 Latvia 3.7 Sweden 16.2 Bosnia 3.7 Switzerland 15.3 Chile 3.3 Iran 15.3 Venezuela 3.2 Mexico 15 Armenia 3

Table 9 Continued

Macedonia 13.8 Vietnam 2.8 Norway 13.3 Croatia 2.8 Montenegro 13.3 Slovak Rep. 2.7 Malta 12 Romania 2.7 Australia 11.5 Finland 2.7 Azerbaijan 10 Ukraine 2.6 Belgium 9.9 Panama 2.6 Argentina 9.7 Cuba 2.5 Spain 9.5 Colombia 2.5 Austria 9.1 Russia 2.2 Ireland 9 Poland 2.2 Germany 8.4 Bulgaria 1.9 Syria 8 Malaysia 1 France 8 Estonia 0.8 Brazil 8 Paraguay 0.7 Trinidad & Tob. 7.7 Moldova 0.6 Bolivia 7.3 Peru 0.4 Guatemala 6.5

In the case of leading living organ donation rates in 2014, the ranking is as follows: Turkey (42,5 pmp), Costa Rica (41 pmp) and South Korea (37,5 pmp). Change in leading countries could be explained by some reasons on annual basis however there is no considerable difference between the years listed.12 Major reasons for difference in donation rates are donation regimes, line of descent, legal regulations and black market etc. Regulations in most countries prohibit donations from non-related donors thus living donor rates are primarily affected by family relations. When countries ranked towards the bottom the list are considered, it is also possible to say that most of them are countries associated with a black market. Level of economic development and legal regulations play a decisive role on donation rates. The reasons affecting donation rates will be examined in the following sections.

4.1. Supply of Transplantable Organs

Kidney demand exceeds the supply (Leider and Roth: 2010). The number of donated kidneys for transplantation is not sufficient to cover the need (Ruth et al.: 1985, p. 515).

12These data are taken from www.irodat.org reports. Reports include other type of organ donations for over 80 countries. 32

Kidney demand for transplant far exceeds the supply and it is not met via donations from deceased people (Wallis et al.: 2011).

When a donor is found, the following problems or problems related to the following may arise:

. Transplantable organs . Approval of next of kin . Legal procedures to be handled . Availability . Organization . Time

4.1.1. Transplantable Organs

Number and variety of transplantable organs increased considerably after the declaration of the “Harvard criteria of brain death”, which is accepted in most countries. “Brain-stem death usually occurs as a result of raised intra-cranial pressure as a consequence of an intra-cerebral bleed. It is well recognized that brain death induces an autonomic storm inducing cytokine release” (O’Dair: 2007, p.6). Although there are controversies about the definition of brain death, general definition focuses on the following two subjects: (i) loss in cerebral function with the death of all central neurological tissues and (ii) the demonstration of any cerebral function precludes the diagnosis (Power and Van Heerden: 1995). One of the major source of transplantable organs is donors after brain death (DBD). The reasons of brain death, before organ removal, are important. DBD organs result in increased and more severe episodes of acute rejection after transplantation (Pratschke et al.: 1999). So, grafting an organ from DBD needs special expertise and diagnosis.

Another source for transplantable organs is donors after cardiac death (DCD). Death based on the basis of irreversible cessation of circulatory and respiratory function (cardiopulmonary criteria) is called “cardiac death”. About three of every four transplantations are recovered from deceased donors (Steinbrook: 2007). A conference, convened in Philadelphia in April 2005, concludes that pulling the plug of a brain-dead patient under morally acceptable circumstances would contribute to an increase in the number of deceased donors for transplantation (Bernat et al.: 2006). OPTN and UNOS

published the Elements of Protocols for Recovering Organs after Cardiac Death in March 2007 which became effective on July 1st, 2007.

Transplantation from DCDs is more cost-effective when compared to transplantation from

Figure 4: Elements of protocols recovering organs after cardiac death. Source: Steinbrook (2007, p. 212)

DBDs (Snyder: 2013). DCD kidney recipients were recorded ten times more likely to require temporary renal replacement therapy post-transplant than recipients of DBD kidneys (Snoeijs et al.: 2010). There is no direct relation about the increase in DCD results with the decrease in DBD (Evenson: 2011). Ledinh et al., and Koffman found that establishment of a DCD program enlarged the donor pool and did not have any negative effect on DBD program (Ledinh et al.: 2010, Koffman: 2003, Akoh: 2012, p. 86)

4.1.2. Approval of Next of Kin

In general, there are two types systems applied in the world: opt-in system and opt-out system. With some exceptions13, these systems require the approval of a relative. There are ongoing debates about the ethical issues of cardiac death and brain death. For the declaration of cardiac death, sufficient time (generally it is about 5 minutes, but not less than two minutes) and the absence of cardiac activity which generates a pulse or blood flow are required (Bernat et al.: 2006, De Vita: 2001). However, there are many examples on return-to-life after declaration of cardiac or brain death. Especially in the coma involved cases, patients could “come back” after bedded in intense care units (ICU) for years. Thus, some physicians and nurses continue to have concerns about the ethical aspects of making the decision of declaring cardiac or brain death of a patient which they consider is related to their mission as medical professionals (DuBois and DeVita: 2006).

“Dead donor rule” declares that donation should not cause death (Childress and Liverman: 2006, p. 82). However concerns are raised because of some counter examples (Steinbrook: 2007, p. 211) in which surgeons may have “forced” potential donors to recover the organs immediately (Chawkins: 2008).

“The perception of some physicians and families is that the end-of-life experience is changed because organ procurement begins immediately after death occurs. However, many families find great solace in donating organs under such special circumstances” says Sue Mcdiarmid in an interview, a surgeon at the University of California (Steinbrook: 2007, p. 211).

13 Especially in opt-out system, doctors cannot be sued for not searching family approval if there is no spouse or next of kin before the surgery. 35

It is not an easy decision for next of kin while they are grieving. They are apt to believe that by donating the organs of their beloved, they do something noble (Barber: 2007, p. 36). Deceased donation in Turkey is almost 20% of all donations, which indicates that Turkish people are not eager to donate the organs of their beloved ones. It is likely that if the diagnostic criteria and brain death procedure declare clearly, the availability of transplantable organs would increase (Sert et al.: 2013).

The reasons of less donation rates are explained by Sert and his colleagues. According to their study, the first reason is that there is no real attempt to address the issue of refusal of the family. The second reason is the absence of an adequate public discourse. Finally the third reason is addressed to be the influence of cultural and religious perspectives on perceptions of the concept of brain death (Sert et al.: 2013).

4.1.3. Legal Procedures

Physicians perform a three-stage brain death test. At the first stage, some basic reflexes are tested. If the patient does not respond, they skip to the next test. At this second stage the patient is connected to a ventilator and an “apnoea test” is started. The patient is disconnected from the ventilator and observed up to ten minutes. At the last stage, physicians try to see whether the patient is ready for the recovery of organs. Physicians wait 6-24 hours (it depends on the country and the age of the patient) to observe the patient (Margarida et al.: 2009, p. 25).

In Turkey, precondition for diagnosis of brain death is defined in the regulation as follows in the Official Gazette issue: 28191, on February 1st, 2012:

a) Reason of coma must be determined, b) Brain damage must be determined as widespread and irreversible, c) Central body heat must be ≥ 32 °C, d) Hypotensive shock table must exist, e) Provided reversibility from coma with drug effects and intoxication must be excluded, f) Metabolic, electrolyte and acid-base disorders must not be detected those explain clinic table independent from brain damage.

If all these conditions are satisfied, the following shall be examined for the diagnosis of brain death:

a) The absence of deep coma (full state of unresponsiveness; not responding to central painful stimuli) b) The removal of brain stem reflexes;

i. Pupillary are unresponsive, midline and duality to bright light (4-9 mm), ii. Absence of oculocephalic and vestibulo-ocular reflex, iii. The absence of corneal reflex, iv. The absence of pharyngeal and tracheal reflexes,

c) The absence of spontaneous breathing effort and positive apnea test.

For the case of a deceased donor of cardiac death, death report requires at least two physicians which is a key issue. The individual should be observed for 5-minutes (Sherar: 2012, p. 17). “The purpose of the 5-minutes observation is to confirm the irreversibility of cardio circulatory arrest before organ procurement; blood pressure is defined as an arterial pressure that generates anterograde circulation. The preferred method to confirm the absence of blood pressure is by arterial line monitoring.” (Shemie et al.: 2006).

5-minutes observation is legally vague. Downie et al., states that there is no reason to believe in this 5-minutes standard procedure. Institute of Medicine Report recommends a 5 minute waiting period while Pittsburgh Protocol requires 2 minute and Swedish law mandates 20 minutes of asystole elapse before death is legally declared (Downie et al.: 2008).

In Turkey, the declaration of brain death is determined by the law published on May 29th, 1979 in the Official Gazette with Law no: 2238 Article No.11 required full consensus of 4 doctors including neurologist, neurosurgeon, anesthesiologist and intensive care unit specialist. Today, declaration of medical death is possible in the presence of two doctors, one of which must be a neurologist or neurosurgeons and the other has to be an anesthesiology and reanimation or intensive care unit specialists which will judge with medical-based rules in full consensus. “With the exception of two countries, declaration of brain death requires 2 doctors instead of 4 throughout the world. In every developed country this figure is 2” says İrfan Şencan, the manager of the General Directorate of

Health Services in Ministry of Health14. According to Şencan this regulation eliminates time loss and expedites the process.

4.1.4. Availability

Availability is a problem with both parties: availability problem of the patient and availability problem of the donor. No matter the patient is in the waiting list, s/he could not be medically available for operation. Waiting lists comprise two subcategories those are active and inactive. Active patients, who are in temporarily acute condition and thus are suitable for transplants are not eligible to receive kidney from deceased donors until they become available. As of 2011 more than 30% of the waiting list candidates were inactive in the U.S. (Grams et al.: 2013).

Availability of the donor is another issue. Although the patients are asked whether a living kidney donor or a deceased; usually from their family owing to medical rules are available. They have to wait for a proper deceased kidney donor unless their potential living candidates could donate and be medically available (Howard: 2007, p.26). According to the UNOS Bulletin in 1997, inadequacy of supply on cadaveric organs results with 4,000 deaths per year as patients are unable to obtain needed organs on time (Adams and Kaserman: 1999).

The governments try to increase the donation rates, especially from deceased donors because there are two or more transplantable organs involved. But increase in life expectancy, diabetes, obesity and alcohol related liver disease contribute both to increase in demand and decrease in the number of available organs (Levitt: 2015).

4.1.5. Organization

Transplantation of an organ must be well-organized and requires special expertise. Donation and transplantation are attempted to be standardized globally by the WHO Guiding Principles of Human Cell, Tissue and Organ Transplantation (WHO: 2010) that was endorsed in the 63rd World Health Assembly (WHA) Resolution (Mondaile: 2010). In addition to many other items not mentioned here, 63rd WHA Resolution urges member

14 http://www.hurriyet.com.tr/beyin-olumune-artik-4-yerine-2-hekim-karar-verecek-25499459 38

states and thus governments “to promote a system of transparent, equitable allocation of organs, cells and tissues, guided by clinical criteria and ethical norms, as well as equitable access to transplantation services in accordance with national capacities, which provides the foundation for public support of voluntary donation”, and “to strengthen national and multinational authorities and/or capacities to provide oversight, organization and coordination of donation and transplantation activities, with special attention to maximizing donation from deceased donors and to protecting the health and welfare of living donors with appropriate health-care services and long-term follow up” (Delmonico et al.: 2011, Sixty-Third World Health Assembly: 2010).

Figure 5: WHO Guiding principles on Human Cell, Tissue and Organ Transplantation Source: Delmonico et al. (2011) 39

Human Development Index is directly related with deceased donation activities and establishing and maintaining a deceased donor indicates a level of development (Caplan et al.: 2009). Medina-Pestana gives a brief description of the organization of the Brazilian system. He states that the country is divided into 27 states (Medina-Pestana: 2006) where Ministry of Health organizes and controls each state and links them up with university hospitals. Each state establishes regional lists of transplant candidates. Allocation is centralized by the State Health Secretariat and supervised by the General Office. Almost all transplantation operations are performed in public hospitals (Medina-Pestana: 2004).

Allocation of the limited supply of transplantable organs is handled through non- governmental organizations like OPOs that are based on OPTN policies. These procurement organizations try to make the clinical match, perform antibodies and manage waiting time. In the U.S. the organ procurement and distribution system is operated by 58 private OPOs all of which have a contract with the federal government. Each OPO is unique in its territory and works with transplant hospitals and makes arrangements to allocate organs across regions for waiting lists in that area. Regional variations exist and this difference influences waiting time for a kidney (Hirth: 2007).

In Turkey, Ministry of Health is the authority responsible for the procurement of organs. The country is divided into 9 regions and there are National Coordination Centers in every region. The regulations of allocation will be discussed in Chapter 6.

4.1.6 Time

Classical donation types are living, deceased heart-beating and donation after brain death. Transplant programs are increasing the donation after circulatory death (O’Callaghan et al.: 2014, p. 130). Grafting and transplanting a kidney takes time and this interval is precious before the organ starts to deteriorate. Deep hypothermic circulatory arrest (DHCA) leads to metabolic problems within renal cells because of the absence of oxygen and nutrients. Calne et al., showed that simple ice cooling could preserve renal functioning for 12 hours (Calne et al.: 1963).

The developments in preservation solutions enabled longer storage times (McAnullty et al.: 2002). However, hypothermic preservation may lead to the following:

. Cell swelling . Acidosis . Altered enzyme activity . Formation of reactive oxygen species

There are some important solutions in international clinical practices such as:

. Eurocollins solutions . University of Wisconsin solutions . Histidine-Tryptophan-Ketoglutorate solution . Hyperosmolar Citrate Solution . Celsior Solution . Institute Georges Lopez-1 Solution

These are the footsteps for the final solution of cold ischemia15 (O’Callaghan et al.: 2014, p. 132).

15 This thesis focuses on the economic aspects of kidney transplantation. For further information, please refer to the References. 41

PART II: ECONOMICS OF KIDNEY DONATION

5. DONATION SYSTEMS AROUND THE WORLD

After the transplantation became an applicable treatment, The Transplantation Society generalized an altruism model in 1985 (WHO: 1994, p.463). Definition of this altruism received broad consensus in the transplant society and was codified as the “default method” of organ supply around the world (Delmonico: 2008). According to Hagai Boas, who used data of 30 countries between 1995 and 2007, the supply of human organs is undergoing a dramatic transformation from generalized altruism towards one-to-one altruism and organ supply is more dependent on direct donations (Boas: 2011).

Almost every government is trying to develop policies for increasing this supply. Kidney diseases take down a huge part of health budgets. Transplantation is the unique treatment/cure for ESRD and every successful operation will decrease the health expenditures of governments. Dialysis sessions of kidney patients are not effective enough to recovery therefore governments have to focus on increasing donation rates. There are different kinds of regimes for donation. Some of them concentrate on deceased donors and some others target both deceased and living donors.

5.1. Deceased Organ Procurement Policies

Deceased donation is the main source of kidney availability where there are several factors affecting cadaveric donations. These are classified as legislative regulations, GDP, health expenditures, wealth level, religious concerns and social norms, educational infrastructure and medical infrastructure (Abadie, Gay: 2006).

Every transplantation policy is based on the following three conditions: equity, efficiency and cost-effectiveness. Although it requires a sharper definition in the literature, equity

basically means that the people are not classified as per their features and every individual is treated in the same manner regardless of race, religion or any other difference.

Efficient relates to the allocation of donated kidneys. The distribution of kidneys is another problem and this distribution requires efficiency. Cost-effectiveness involves comparison among available or applicable policies. A policy could be more effective than another one with respect to costs or number of transplants. Hence evaluation of policies requires the consideration of cost-effectiveness.

5.1.1. Presumed Consent

In presumed consent (opt-out) system, the deceased donor is legally assumed as a donor unless stated otherwise before death (Abadie, Gay: 2006). The person is obliged to sign a statement that s/he is not donating his/her organs. Default policy assumes that if a brain- dead person is available for recovery of organs, they will be removed without permission.

Abadie and Gay (2006) found out that presumed consent gave rise to an increase in donation rates between 25-30% in 22 different countries. This is considered as a significant role for increasing donation rates (Johnson, Goldstein: 2003, Neto et al.: 2007). Bilgel (2011) found that countries employing presumed consent regime have 5.3% higher donation rates on average in comparison to countries those do not. This system was first employed in Spain and is called as the Spanish Model. Besides, countries enact other legislations coming into force during the application of the Spanish Model (Healy: 2005). They ask for family approval and thus the system is not considered as full presumed consent. Bilgel discusses the fact that objections of families affect donation rates. Bilgel states that in cases family approval is asked, donation rates would increase by 8%. Rithalia et al. examined the outcomes of a regime change in donation from informed (discussed under the following heading, Section 5.1.2) to presumed consent in three countries (Spain, Belgium and Austria) and concluded that the donation rates in these countries increase between 2.7 and 6.14 pmp (Rithalia et al.: 2009). Bilgel also proposes that hospital crew is a key component in increasing donation rates through affecting the decision process of a family regarding donation (Bilgel: 2011).

Rosenblum et al. analyzed the aspects of the approval of next of kin for deceased organ donation. They found out that, among the analyzed countries 25 countries were employing

a presumed consent system. Their research also revealed that, except for Belgium, Finland, Singapore and Sweden where the authority has the right to veto the rejection of next of kin, all countries ask for the approval of next of kin (Rosenblum et al.: 2012).

Presumed reciprocity is another kind of system which is based on presumed consent however there is a small difference. Declaration of being a non-donor is accompanied by the loss of priority in receiving an organ in case the declarant needs an organ for transplantation in the future. The probability of being available for donation after death is much higher than probability of having kidney disease (Kolber: 2003).

5.1.2. Informed Consent

According to the informed consent regime, a person indicates his/her wish to become an organ donor after death upon registration by family members (Horvat et al.: 2010). There are three basic components of informed consent which are given to be prerequisites, information and decision (Beauchamp et al.: 2001, p. 80). Prerequisites encompass two main conditions about: competence (i.e. donors have the ability to understand and decision-making ability) and voluntariness (i.e. lack of constraint and undue pressure). Information is essential and healthcare professionals must inform the donor properly and explicitly. If the information is ensured and donor has accepted to donate his/her organs, the final step becomes applicable (Petrini: 2010).

Another form of informed consent system is informed reciprocity. It suggests that if one accepts to be a donor, s/he will be registered to the system and if s/he needs transplantation, s/he will have priority. If any need for transplantation does not arise, organs will be transferred to a pool for the sake of other beneficiaries. Robertson proposes that an informed reciprocity system would respect autonomy, eliminate injustice and minimize shortage (Robertson: 2007).

However, there are some concerns about this system. Someone who already has a renal disease may attempt to enter the system which could be deemed as a deception. In order to avoid such, people already with a disease must not be allowed to register. Thus managers of the system have to carefully examine the medical history of the potential donor.

Another matter regarding the system is the family veto. The system does not give the family the right to reject. Therefore, the family’s judgment is ignored. Donation pool is also a critical issue for this system. At this point it becomes clear that over/undersized pools would not serve the purpose. In case of a large pool, the patient who needs an organ (and also who is a donor) will stay for a long time in the waiting-list while donation will be meaningless for the patient in a small pool. Finding a transplantable kidney takes time and therefore donation pools require effective arrangement for an effective system.

Organization of the allocation and listing is another issue. As a matter of course governments are the authorities in charge, however this can be (and is) handled by government supported special purpose organizations and/or NGOs. (Kobler: 2003).

5.1.3. Mandated Choice

In the mandated choice regime, every available citizen makes a decision either to become or not to become a donor. Citizens under 18 years are not included they make their decision when the time for having a driving license or any other legal task comes.

Mandated choice system dictates a choice. The preference of deceased person is already known there is no need for family permission and the issue of time losing through looking for a family approval is thus eliminated (Hansmann: 1989, p.15). However a mandated choice poses the risk of lower the donations since donation is a systemic constraint and people who do not choose to become a donor naturally choose not to become a donor, which translates into lower rates of donation. Alternatively, individuals can refuse to make a choice either. Thus, in Texas; 80% of citizens registered as non-donor in 1995 and in Virginia 24% of citizens refused to become a donor in 1999 (Siminoff and Mercer: 2001, Klassen and Klassen: 1996). Therefore, mandated choice may not be as effective as expected.

On the other hand, this kind of a regime can be considered as a cost-effective regime. There is no need to organize campaigns or activities for awareness. Under this regime, allocation could be handled in the same manner as it is handled today16 (Bilgel: 2011, p.29).

16 See “Kidney Allocation Principles”, Section 8.3. 45

5.1.4. Enforced Donor

In this regime, every citizen is naturally a donor. In the case of death of a citizen with suitable organs for removal, no denial of any kind neither from the family or any other kin is regarded. This regime involves enforcement therefore its employment could also be coercive.

In spite of the above mentioned, the main benefit of this system is the high possibility of increasing the donation ratio. Currently, almost half of the organs suitable for removable cannot be recovered because of the disapproval of the family (Sheehy et al.: 2003). Another benefit is that, as in the case of mandated choice mentioned before, there is no need for campaigns and this concludes that the employment system is almost costless. Not taking the approval of the family makes it a time-saving system. Besides no donation cards or special training for doctors in order to persuade families are required. The pressure on families in terms of making a decision about donation is also released.

5.2. Monetary Incentive Mechanism Regimes

Paying for an organ or selling an organ seems unethical for the vast majority. Since an organ is the part of body, selling an organ most commonly is considered as selling the body. Yet there are some mechanisms those pay for an organ and these mechanisms function under the term “incentive”. However, it is still altruism because it is non-coercive and donation is on voluntary basis. The following sections discuss the details of systems based on incentives.

5.2.1. Free Market System

In the economic theory, closing the gap between supply and demand is possible in the market itself. Whenever there is an opportunity to make profit in the market, players try to make use of this situation. However in the case of organ shortage, this gap cannot be closed owing to the current market mechanisms, since organs are not tradable and therefore the gap keeps growing in time.

In the altruistic system, donors do not have any economic benefit but only have the moral satisfaction of granting life. On the other hand patient has a longer and healthier life (which

can be counted as a gain), hospital and surgeons receive their payments. If a patient is transplanted a functional kidney (i.e. transplanted kidney does its function efficiently and properly) the government will no longer make payments for dialysis so the government will decrease its expenditures (which is a gain for government and/or insurance companies). Pharmaceutical companies and pharmacies those sell drugs, which are subject- based products and are only available for transplant patients and donors (such as immunosuppressants), as well as medical device companies also have their gains before, during and after transplantation. .

In the altruistic model, the officer in charge could act reluctantly for inviting a grieving family for donation. On the other hand, in the case of an established and legally recognized free market, the family could volunteer to donate. It is actually a donation because whereas the organ is sold, it is voluntarily given for the sake of another person by the free decision of next of kin. Therefore, a free market system would increase social welfare and efficiency (Bilgel: 2011).

Initial supporters about market-based solutions were Schwindt and Vining (1986), Hansmann (1989), Kaserman and Barnett (1991), Peters (1991). Altınanahtar et al., aimed to estimate a supply response to monetary incentives to donate organs by replicating the survey of Adams, Barnett and Kaserman (Altınanahtar et al.: 2008). They tried to reach to a usability rate for market-clearance. Kaserman, Barnett and Adams argued that freely adjusted market fluctuations would ensure equilibrium in supply and demand. Accordingly, they argued that all consent regimes are socially inferior but incentives to deceased donor family would increase donation rates. Fluctuation on incentives will stand on an average price according to supply and demand (Barnett and Kaserman: 1999).

A survey conducted at Auburn University by Kaserman and Barnett concludes that the equilibrium price is less than $1,000 (Kaserman and Barnett: 2002). On the contrary, the same survey conducted by Wellington and Whitmire with a wider range revealed a very high equilibrium price which is approximately $144,000 (Wellington and Whitmire: 2007). One other survey from Uludağ University of Turkey ended up TRY 5,000 (USD 2980)17 as the equilibrium price (Bilgel: 2011).

17 http://www.x-rates.com/average/?from=TRYandto=USDandamount=1andyear=2011 47

The free-market system offers the option to choose a proper and a healthier organ. Price of an organ may increase as demand increases therefore adjustment mechanism for the clearing price is required.

Another argument against the free-market system is about the sellers. It is claimed that those who accept to sell their kidneys will mostly be poor and desperate people. Cohen examined people selling their organs in 6 countries; three countries in South Asia, Egypt, Iran and Philippines. He concludes that Pakistan is one of the largest hosts for transplantation centers in the world and selling body parts in Bangladesh is a growing sector because of the low rate of income where 78% of citizens earn less than $2 per day (Moniruzzaman: 2012). In India, there is a significant trade already going on in terms of selling kidneys (Cohen: 2013).

Transplant tourism and organ trafficking focus on poor people. It is easier for middle men to find a seller in rural areas. This situation is justifiable because although selling part of one’s body is the last thing to consider, desperate and hopeless people may have to reach to this end. The decision is irreversible and the seller cannot replace the recovered organ. Therefore, transplant tourism and organ trafficking researchers basically target people in poor countries, so do the researchers. Mendoza studied Philippines (Mendoza: 2009), Cohen examined India, Bangladesh and Philippines (Cohen: 2013), Scheper–Hughes analyzed India and China (Scheper-Hughes: 2000) and Yea also studied Philippines (Yea: 2010). In light of numerous articles about organ trafficking, Chapter 7 covers a brief discussion regarding this issue.

In the free market regime, buyers will be able to access the kidney they need and which they can afford. The buyer would be making the payment or it may be covered by their insurance system (as it is the case in Israel). This results with a gain for all the shareholders. Patients will get healthier kidneys, insurance companies will not be paying for dialysis, governments will not face a loss of labor and the donors will have got some money in return.

5.2.2. Government Monopsony

The government monopsony is the regime that price of an organ is valorized by the government or a single entity authorized by the government. This system was first

proposed by Becker (Becker: 1997). Details of the system may be outlined by governmental authorities; for instance part of the incentive, fixed at a certain amount by governmental regulations, might be payable to next of kin or direct payment at all could be made.

The phrase “selling an organ” sounds grave, thus some authors use different expressions like “rewarded gifting” (Daar et al.: 1990), “ethical incentive” (Delmonico: 2002) or “compensation for personal suffering” (Gutmann: 2002), however each statement declares the main idea that the payment is not for the organ and it is a reward to the donor. Clarification of this expression is important because governments do not buy or sell the organs, they organize the parties and regulate the system. Gaston et al., proposed limitation of rule based financial disincentives (Gaston: 2006). In March 2002, more than 100 transplant society members gathered in Philadelphia and proposed a system to be designed by government. Final declaration of the conference was published as The Report of a National Conference on the Waiting List for Kidney Transplantation (Gaston et al.: 2003).

The main advantage of this system is a fixed price together with steady and solid allocation. Besides, the black market can be suppressed through the employment of the system. The system is easy to adopt as in the form of either an opt-in or an opt-out regime. Since it is flexible in terms of adoption and application flexibly, updates and transition would not take time. If the system is publicly announced comprehensively covering all aspects there would be no perception as if the system is of disrespect to the memory of a deceased.

Capron et al., emphasized that regulated markets bring other problems beyond the damage to sellers. The system would be very expensive and complex to administer. Accordingly, a regulated payment system would not increase the supply of organs (Capron et al.: 2014).

Government monopsony is less efficient than a free market system. It wouldn not let price fluctuations and thus will repress supply. In cases the next of kin is aware that the organ(s) of deceased is compatible with anybody, they would most likely demand more money for the organ (Bilgel: 2011).

5.2.3. Reimbursement System

The reimbursement system proposes an indirect incentive to the donor’s family such as tax deduction or payment for hospital and funeral expenses. Tax deduction system aims tax refund for the deceased and relatively less tax refund for the family. Oswald proposes a small incentive for becoming an organ donor at the phase of obtaining driving licenses. He suggests that almost $15 of a tax deduction will cause a huge tax-loss however available transplantable organs of deceased people will save more than the tax-loss (Oswald: 2008). Actually some Acts regarding this matter such as the Help Organ Procurement Expand Act (2001) and the Gift of Life Tax Credit Act (2001) are in force in the U.S. According to these acts, there is a $10,000 tax refund for deceased donation and $2,500 for living donation (Bilgel: 2011). Nevertheless, there are some opponents to tax deduction. Delmonico (2002) and Calandrillo (2004) argue that tax deduction may cause an inequality between tax-payers. Delmonico et al., opposes tax credits since regulatory authority tries to assign an arbitrary value for a donated organ (Delmonico et al.: 2002). Caladrillo explains that tax deductions could lead to inequality because they are regressive (Calandrillo: 2004).

Hospital and funeral expenses are huge cost items especially for lower income citizens. Some of the researchers propose a support for these costs in return of organ donation (Hansmann: 1989, Howard: 2007, Abouna: 2008). This is considered to be much more acceptable since there is no direct payment or an advantage for spouses. Delmonico et al., argues that the funeral expenses are not as much to talk about therefore it cannot be considered as an incentive and this kind of a reimbursement could be made voluntarily as an act of social state (Delmonico et al.: 2002).

Moorlock et al., argue the cause and effect relation of payment for funeral expenses and its impact on donation rates in consideration of Nuffield Report (NCON Bioethics: 2011, Ch. 5) also offer an extra payment in addition to funeral expenses (Moorlock et al.: 2012).

Since the consent/approval of next of kin must be taken after brain death as the donor is still connected to the ventilator, another argument at this point is raised regarding the timing of the donation on the basis that donation under these circumstances may causes early death. Any little possibility of recovery is eliminated in doing so which would in some sense be a premature termination. Such enforcement could affect doctors to make an early brain-death declaration (Barber: 2007, pp. 27-30).

5.3. Future Delivery Market

5.3.1. Opt-in Future Contract System

This system proposes that people sell their organs to an entity for delivery after death. It is a future-contract that is agreed upon payment to family after death occurs. Mode of payment is an issue of negotiation, either in installments or in cash all at once. Family right is restricted with this contract. The contract would be renewable as long as the donor agrees. Hansmann and Cohen propose a free market constructed by insurance companies offering different amounts payments (Hansmann: 1989, Cohen: 1989).

According to Bilgel, the effectiveness of an opt-in future contract depends on the amount of altruists existing in the market and the structure (Bilgel: 2011). Byrne and Thompson argue that insufficient supply could be solved by the exclusion of the next of kin approval in addition to making an irreversible contract with the individual or making post-donation payments to the next of kin (Byrne and Thomson: 2001).

None of the propositions guarantee an effective distribution of organs. It is obvious that insurance companies will look to obtain these organs primarily for their clients. For a proper application of this contract, the next of kin should be removed from the decision- making process.

5.3.2. Opt-out Future Contract System

Opt-out system requires registration and a yearly basis fixed payment to an authorized agency/company to become a non-donor. It is considered that in order to become a non- donor or an opponent, one must have strong reason to not to donate and to pay a premium. Such a reason would either be cultural or religious or personal but apparently it will be against the system. It is evident that in case the premium is high, people will tend to deceive the system as not being suitable for donation, in order not to pay the premium. As a final matter; people are indifferent in each system therefore the donor pool will enlarge in the opt-out system. Becoming a non-donor is a matter of having the ability to pay. Thus, a citizen who wants to be a non-donor or does not want to be a donor, has to have financial strength otherwise s/he is presumed a donor.

In contrast to opt-in regime, opt-out regime should involve the decision of the family. A donor registered as a donor, either with his/her will or not, is presumed suitable for donation. In case there is a family objection for removing organs, then the family has to make the insurance payment to the system. This regime does not deal with the allocation problem. Allocation system can be organized as it is today. Therefore, it is ineffective in terms of distribution (Bilgel: 2011).

5.4. Living Organ Procurement Policies

In the case of living organ donation, organs those can be donated are very limited. Most of the body parts – such as liver, lung, cornea, tissues, arms, face etc. – are transplantable organs only from deceased donors while living donors, in general, are capable of donating one kidney, part of liver and some types of tissues. Kidney transplantation comprises the majority among all organ transplantations. Living organ donation is a critical issue in terms of the number of transplantable organs where the number of donated organs from deceased donors varies

There are two transplantable kidneys from a deceased donor but preservation, transportation, transplantation and time are very important issues. However in the case of a living donor these problems can be eliminated or minimized. Survival rates indicate to a great advantage in transplantation from living donation. Notwithstanding surgery risks, the survival rates are incredibly high. Death during transplantation is approximately 0.1% in the world and in Turkey it is even much less (0.03%-0.04%).

Another advantage of living donation is about compatibility. Vast majority of living donations are from spouses, family members or next of kin; so the probability of organ rejection is very small. Besides, finding a compatible organ from the family is much easier than finding a proper deceased organ.

Ease in technical preparation is one other advantage offered by living organ donation. Organs of a deceased donor must be transplanted within 72 hours under cold ischemia. Moreover, some tests and preparations those have to be made are included in this very limited 72 hours. However, in living donation, these tests and preparations take almost 3 weeks. Cold ischemia is not needed for living donors. Such a time-period would increase the success ratio of the surgery and compatibility of the transplanted organ.

Living donors may face some health problems and some after-surgery complications however long-term risks are extremely low. Recent surgical techniques such as robotic donor nephrectomy and laparoendoscopic single-site donor nephrectomy lower the risks to a minimum (MacConmara and Newell: 2013, p. 115). Some reports reveal that living kidney donation is not affected by risk of death, renal disease or renal failure possibilities (Segev et al.: 2010; Ibrahim et al.: 2009).

In the case of an organ procurement from a deceased donor, confirmation of donor is not clear and verified (whether s/he was a donor or not; final decision is made by next of kin) while in living donation cases, the donor expresses his/her preference to donate (Bilgel: 2011, p. 93). Also, s/he has the right to withdraw from the system and refuse the operation until the beginning of the surgery.

5.4.1. Policies Based on Monetary Incentives

Results obtained by some authors, which are given in the Free Market System section (5.2.1) of this thesis reveal that different amounts of incentives could be effective to increase living donations The Working Group on Incentives for Living Donation recently declared that incentives have to be at an adequate amount (Matas et al.: 2015). From existing markets, the Working Group aligns that some individuals in all societies may be willing to sell a kidney depending on: (a) preferences regarding kidney selling or other available income-generating options (b) the amount of incentive offered (c) economic status and immediate financial needs of individuals and their dependents (Martin and White: 2015).

5.4.1.1. Government Monopsony

In the government monopsony system, government determines a fixed price for buying and selling organs. All rights are reserved by the government or an institution that is authorized by the government. The system offers a fixed price for related and unrelated donors. The main problem with the system is the allocation problem however the same allocation method in non-monetary systems is fully applicable.

Commercialization of an organ is a debated and disputed issue because of ethical concerns and therefore policies employed by governments are vulnerable in this sense. Iran is the 53

only country where buying and selling kidneys are legal in a system called The Iranian Model. In early 1980s, the Iranian government recognized the heavy burden imposed by dialysis expenses and started paying for living related transplants abroad, especially in the U.K. (Watts: 2007). As a consequence of the increase in costs, a small network of renal transplant was established from 1985 to 1987. Transplant needs had reached up 25,000 people by that time and most of these were from rural areas without medical care (Ghods and Savaj: 2006). In 1988 Iran legalized living unrelated kidney donation (LURD) and an associated transplantation system (Major: 2008). All transplant patients and donors are matched and managed in this organization that is called The Kidney Foundation of Iran (KFI). This program is monitored by the Iranian Society of Organ Transplantation. Among many restrictions, one important restriction is that the system does not allow foreigners to become donors or recipients (Ghods: 2002; Ghods and Ossareh: 2001; Al-Khader: 2002; Malakoutian et al.: 2007). Other major restrictions are given as follows: (i) the donated kidney must be transplanted to an Iranian citizen (ii) the payment to the donor is made by the government (iii) in general the donor and the patient are not allowed to come together (iv) transplant centers, hospitals or doctors do not have a right to interfere in the organ matching period (v) the donor is granted a health insurance after the transplantation (vi) payment to the donor can be made from a charitable organization (Hippen: 2008). Upon the development of this model, the waiting list was eliminated in 1999. In order to prevent organ trafficking, middlemen are not allowed in the system.

Malakoutian et al., examined the socioeconomic status of 478 Iranian living unrelated kidney donors between October 2005 and March 2006. They reached to the following results; 82% of the donors were married, 79% were breadwinners, 6.5% were university graduates, 62% were living below poverty line and KFI involvement of the donors was 96% (Malakoutian et al.: 2007). Similar research was conducted by Mousavi et al. in 2013 on 167 donors and they found out that that 55.7% of the donors were married, 2.9% were university graduates, 60.5% were motivated by financial disabilities (Mousavi et al.: 2013). The results of these two analyses show that demographic and socioeconomic structure of the donors underwent through a changed in this 6-years period.

5.4.1.2. Reimbursement of Living Donors

There is a significant distinction between deceased organ donation and living organ donation. Deceased donor is a cadaver and the body will be useless if buried or cremated whereas living donor will continue living after surgery. So, living donors require utmost attention and preparation before and after surgery. First of all, after transplantation (kidney donors are of concern in this thesis) the living donors lose their kidneys which may be associated with health problems such as fatigue or loss of strength. As a second matter, after-surgery medications and medical examinations are needed and they have to use some drugs and immunosuppresives to recover. There are other losses such as earnings, time, and disruption of insurance policy. The reimbursement of living donors can be considered as payment for these losses. This compensation could include earning-losses, travel costs, lodging, health insurance and even university tuitions as well.

Gill et al., states that the Canadian Government is partially responsible for funding healthcare, oversight and administration of health services including organ donation in some provinces (Gill et al.: 2014). Barnieh et al. reported that nearly 70% of Canadian citizens accept financial incentives for deceased donors and almost 40% accepted becoming living donors (Barnieh et al.: 2012). In order to assess a value of reimbursement Becker and Elias (2007) focused on the losses of donors and concluded on an optimal incentive value of $37,600 (Becker and Elias: 2007). Gaston et al., (2006) proposed $23,525 of an incentive at all with additional tax-deduction including the pain and anxiety of the donor. Matas and Schnitzler (2004) analyzed the cost-effectiveness of kidney transplantation and concluded with a break-even point of $78,816 and cost-effective payment of $224,432. The authors focused on the components of transplantation with respect to donor and recipient.

Hoeyer et al., made a detailed literature analysis about public attitudes toward financial incentive models for organs (Hoeyer et al.: 2013). Further, they classified the articles according to financial incentives (FIs) in living and deceased donation. Their research reveals that governmental FIs vary considerably between 25% and 60% and there exists a similar discrepancy regarding the idea that recipients should compensate the expenses which are below 10% to over 55%. Bosisio et al. (2011), Danguilan et al. (2012), Decker et al. (2008) and Haddow (2006) published articles those conclude with relatively low support for the idea that donor should receive cash or lump sum payments. According to

Boulware et al. (2006), Mazaris et al. (2011) and Neuberger et al. (2003) and Leider and Roth (2010), basically there is consensus on the compensation of medical expenses with a ratio between 60% and 91%. Their analyses reveal that other studies propose agreement on higher figures for altruistic living donation at a ratio between 51% and 89%. Following figures show the difference between willingness to donate altruistically to a relative or to a charity and/or a priority wait-listed patient.

Figure 6: Percentage of approval of different models of FI for LD in comparison to percentage of willingness to donate altruistically to a relative. Source: Hoeyer et al. (2013, p. 353)

Figure 7: Percentage of approval of different models of FI for LD in comparison to percentage of willingness to donate altruistically to a relative or a donation to a charity or getting priority in a waiting list in case one needs later an organ transplant. Source: Hoeyer et al. (2013, p. 353)

Hoeyer et al. concludes that “all version of cash payment (general or different sums) gains much less agreement” and “there is no considerable difference in whether the sum is below €1,000 or above €12,000” (Hoeyer et al.: 2013, p. 354).

5.5. Non-monetary Organ Allocation

There has been a steady increase in number of kidney transplantation but the shortage of available organs and growth in number of patients leads to long waiting lists (Larijani et al.: 2004). The limited kidney supply requires superior allocation and non-monetary allocation systems do not focus on increasing donation rates where the main concern is about the allocation of the donors who are already willing to donate (Roth: 2007). Blood- type and tissue-type incompatibility are the main types of mismatches in consideration of donors and recipients. Between a random donor and a patient, blood-type incompatibility in the U.S is about 35% (Sönmez and Ünver: 2014) and about 11% for tissue-type incompatibility (Zenios et al.: 2001). Every kidney is priceless, thus beyond any price, there must be a proper allocation system not to waste these precious organs.

5.5.1. Pairwise Kidney Exchange

Pairwise Kidney Exchange (PKE) provides a solution to incompatibility between donors and recipients by pairing two incompatible pairs to facilitate an exchange between kidneys of two willing donors (Wallis et al.: 2011). In PKE, an exchange is arranged between an incompatible patient-donor and another pair. In this system the donor from each pair donate their kidneys to the recipient in the other pair (Roth et al.: 2005).

PKE was first suggested by Felix Rapaport in 1986 (Rapaport: 1986) and was applied first in South Korea (Kwak et al.: 1999). The following figure shows the historical evolution of PKE.

Figure 8: Historical evolution of kidney paired donation from its original proposal by Felix Rapaport to present. Source: Wallis et al. (2011, p. 2092)

There are two main factors affecting PKE innovations: the number of servable incompatible pairs and finding best match between participants (Wallis et al.: 2011). Articles of Roth, Sönmez and Ünver, involving mathematics on the principles of allocation algorithm was epoch-making (Roth et al.: 2003). They enhanced the study with principles based on game theory and enlarged their findings (Roth et al.: 2003; Roth et al.:2005; Roth et al.: 2007; Sönmez and Ünver: 2009; Roth et al.: 2006, Ünver: 2007; Ünver: 2010; Kojima and Ünver: 2008).

However this system is vulnerable and there are clear deficiencies. The system mostly comprises related-kidney donors and – since the donation system is based on altruism – any donor has the right to withdraw from the register and refuse transplantation at any time. Owing to this right, the operations must be performed simultaneously and (if possible) in the same center, if not; the centers must be close to each other.

5.5.2. NEAD Chain and Domino Paired Donation

Non-simultaneous Extended Altruistic Donor (NEAD) Chain and Domino-Paired Donation (DPD) – which is a version of NEAD Chain limited to 2 donors and 2 recipients – are other types of non-monetary allocation mechanisms. These systems are developed by Abraham et al. (2007) and Rees et al. (2009) respectively.

NEAD Chain involves “bridge donors” where incompatible recipients receive kidneys before the bridge donor actually undergoes a transplantation operation but allows many incompatible pairs to be transplanted (Aslagi et al.: 2011). Gentry et al., showed that when the chain is limited to three transplants DPD or NEAD Chains would produce more transplants as well (Gentry et al.: 2005). According to Aslagi’s simulation when chain segments include 4-6 transplants NEAD chains produce more transplants than DPD. Initiating chains with an altruistic donor provides higher quality matches to participants and allows more pairs to benefit (Rees et al.: 2009).

The longest NEAD Chain operation was performed in July 2007 which involved six centers and took 8 months. This operation shows that NEAD Chain inherently can extend over an arbitrary period of time and this fact raises concerns about the risk of any donor to exercise his/her right of withdrawal from the register and refuse transplantation. Simulations of Gentry et al., and Asgali et al. show the effective number of the ring of chain. Besides there are other ethical concerns including privacy, confidentiality, exploitation and commercialization (Woodle et al.: 2010).

The schematic representation of exchange systems can be seen in the following figure

Figure 9: Schematic representation of exchange systems. Source: Wallis et al. (2011, p. 2093)

6. ECONOMIC DIMENSION OF KIDNEY DONATION

6.1. Donation In Terms of Basic Economic Theory

ESRD patients may die before a suitable organ is found for transplantation even though the number of transplantable organs are far lower than the needed (Deck and Kimbrough: 2010, p.1). According to Dr. Luc Noel, coordinator of clinical procedures team of WHO, every year almost one million people are stricken with ESRD but very few of them receive renal replacement therapy and kidney transplant (Garwood: 2007).

Governments introduce acts for increasing organ/kidney donation rates. These acts may have a limited effect on donation rates however transplant waiting lists keep extending (Coppen et al.: 2010). The gap between supply and demand for kidneys is growing. When there is a gap between supply and demand, economists usually look for reasons those change the equilibrium of the market (Becker and Elias: 2007). The determinants of supply are limited to the main factor for supply that is altruism. In this context satisfying the demand for kidneys seems impossible.

Some researchers such as Adams et al. (1999), Kessler and Roth (2012), Li et al. (2013), Deck and Kimbrough (2013), Israni et al. (2005), Li (2016), Bilgel (2011) made experimental analysis and empirical observations about organ donation (Hawley et al.: 2010, p.6). Under normal market conditions, there would be supply when there is a demand. On the other hand supply would increase in case demand decreases. This balance is possible under market equilibrium conditions.

Figure 10: Simplified graph of supply and demand

The amount of transplantable kidneys is based on altruism. General form of supply and demand graph depends on quantity and price however altruism does not have a monetary effect. Therefore the y-axis will move in the graph, depending on the change in the time component. Supply of kidney cannot change depending on the price; the graph would be drawn as follows (Becker and Elias: 2007, p. 8):

Figure 11: Supply of kidney used normal conditions

The graph showing the change in supply and demand in Turkey between 2011 and 2015 is as follows.

Number of patients and transplants in years between 2011-2015 8000 7000 6000 5000 4000 3000 2000 1000 0 2011 2012 2013 2014 2015

Number of transplants number of patients added to the waiting list

Figure 12: Number of patients and transplants between 2011 and 2015

The graph shows that the gap between supply (the number of transplantations) and the demand (the number of patients in the waiting list) is growing every year. There are patients already assigned in the waiting list. This graph shows that the demand of patients cannot be satisfied at any time by the current supply of the donors. This fact is almost the same all over the world except for Iran. In order to close the gap, governments apply different methods that are examined under Chapter 5, “Donation Systems around the World” of this thesis.

6.2. Determinants of Supply

6.2.1. Altruism

The first and main determinant of supply of kidney is altruism. The commercialization of an organ is prohibited by WHO in 1985 (WHO: 1994). Although this was a suggestion for WHO members, almost all of the countries take it into consideration and apply altruistic models. Altruism can be named as an ultimate gift: the “gift of life” (Satel: 2008, p. 4). Altruism results with donation when the organ is transplanted to the recipient. Two types

of donation exist; either from a deceased or a living person. Donation systems are already discussed in Chapter 5.

In most of the countries, either applying an opt-in system or a soft opt-out system, the decision to donate organs from a deceased is made by the next of kin. Living donors can be classified into two parts: Living related donors (LRD) and living unrelated donors (LURD). Selection of the recipient is up to preference of the donor. LRDs choose their affinity or spouse; in fact all systems oppose donations to unrelated patients. Most of the donations in Turkey are type LRD because of the legal regulations (IRODat: 2015). Nations who comprise a high living donor-ratio, as in the case of Turkey, have tight relationships of affinity. This type of a selection has another impact on the waiting list. Number of patients in the waiting-list decrease and this causes a social surplus. This kind of altruism results with the benefit of all recipients, either in the waiting-list or the related donee (Epstein: 2008).

Nevertheless, every altruism is not considered an exact “altruism”. Some of them can be deemed as a “solicited” donation. Donations from a deceased could be considered in this sense. Solicited donation can be classified into two parts: (i) the choice of the next of kin of the deceased and (ii) a registered donor (Epstein: 2008, p. 465). If the organs of the deceased are suitable for transplantation, the doctors or physicians would try to convince the next of kin. The spouses could not be eager to donate the organs of the deceased and may not be fully persuaded but in the time of grieving. The pleasure of doing a favor would be considered as a means of charity for the deceased one.

Registering as a donor could be considered as solicited donation. An individual might not be willing to donate his/her organs however s/he might become convinced in time to become donor with the effect of advertisements or any other related factors. Some researches and data show that advertisements and donation campaigns are effective in increasing donation rates. Registered donors comprise the rest of solicited donors.

There is skepticism about solicited donation (Epstein: 2008) which has two negative effects. First, it gives rise to a crowding out effect. The general idea is that; organ of each registered donor would be transplanted, thus one might think no more donations would be needed in case the number of donors is high enough. In fact, organs of all registered donors are not transplantable. The way and the place of death are the two main determinants in

organ transplantation. On the other hand, it is another fact that donations are not at a sufficient level. Actually, it would not be sufficient enough to satisfy the need of kidney shortage even if the available kidneys of all deceased donors were suitably recovered.

This skepticism causes prejudice on unrelated donation. Since unrelated donations are restricted by legal regulations -except Iran- authorities are suspicious about unrelated donations and this type of transplantation demands are thoroughly investigated by a committee. If the underground organ market is out of the equation, transplant centers have to ask and the committee has to be convinced about unrelated donation.

Another important way of increasing the supply of organ is the exchange mechanism. Roth et al. (2005), Ünver (2010), Sönmez and Ünver (2014) and Dominguez et al. (2011) studied on the effectiveness of exchange mechanism and concluded that the system increases the success of the allocation of donated kidneys and hence increases the supply of kidney. This mechanism does not directly affect the organ supply. It is about increasing the efficiency of allocation of limited supplies. Mismatch between a recipient and a donor is normal, however this would not be a problem of allocation. The strategy is simple; matching the proper recipient with the convinced donor. The common way is the pairwise kidney exchange which is already explained in section 5.5.1. Besides, academicians are still working on other allocation methods such as the NEAD Chain which was also discussed in the section5.5.2 of this thesis.

6.2.2. Legal Regulations

The quantity of supply can be affected by legal regulations. These regulations have different objectives such as protecting the right of the donors, supporting the supply of donated organs by encouraging donation and efficient allocation of organs. Another object is to prevent organ trafficking and to guarantee a fair and transparent allocation of organs with legal certainty (Coppen et al.: 2010). Authorities employing the system can increase donation rates. As previously discussed (in chapter 5) in most cases donation rates of opt- out regimes are higher than those of opt-in regimes, with few exceptions, like Greece (Shepherd et al.: 2014, p. 4; IRODat: 2015), however countries like Spain which do strictly employ an opt-out system (IRODat: 2015) are very successful in terms of increasing donations. Transplant and Donation Acts are regulatory and obligatory for the countries.

Unplanned and uncontrolled acts result in organ trafficking and the organ traffickers establish their system in these countries like Bangladesh, Pakistan and India (Cohen: 2013, pp. 270-271). Therefore the effective these acts are, the lower the crime rates.

6.2.3. Effect of Healthcare System

The operational functioning healthcare system could affect the supply of transplantable organs. If the system works properly, donor candidates will have confidence about before and after-surgery medical treatment. They will trust the professionalism of the surgery team and this would eliminate the concerns and hesitations.

A regular working healthcare system can monitor the recipients before they are stricken by a kidney disease. Controlling and monitoring patients (or potential patients) could be classified within preventive healthcare practices which would indirectly affect donation rates. That is, it would not increase the donation rates however would decrease the demand for donation.

6.3. Determinants of Demand

6.3.1. ESRD Patients

Major determinant of kidney demand are the ESRD patients. The disease has 5 stages. Stage 1 and Stage 2 are the early levels and the need for dialysis begins at Stage 3. The patient can survive with dialysis throughout Stage 3 and Stage 4. The last stage of renal failure is called ESRD and at this stage the patient must have transplantation. Waiting lists are the solid evidence of the urgent demand for kidneys. In fact all the dialysis patients are potential ESRD patients. Total demand for kidneys could be translated as the total amount of dialysis patients.

6.3.2. Legal Regulations

Legal regulation is an effective determinant for supply and demand. Tight regulations could have a negative effect and decrease demand. The Organ Transplant Law of Japan was revised in 2010, and the revisions increased the number of brain-dead donors eight times in comparison to the pre-revision. The revision does also include switching the

system from opt-in to opt-out. The revised law permits children below 15 years of age to become donors. Previous law had banned brain-dead donors under an age of 15, thus many children had to look for suitable transplantable organs in the U.S. which was too extravagant beyond being very costly (more than JPY 200 million (USD 2.5 million18) for a transplantable heart from a deceased child (Fukue: 2011).

When China introduced new penalties for doctors and hospitals those generate an income through sales of livers, kidneys, hearts and other transplantable organs recovered from executed prisoners, global trade in organs diminished. This legislation decreased the global demand on China (Watts: 2007).

In Turkey, legal regulations made progress in time. The first legal regulation was made in 1979 (Section 2.2). Until the legislation that was enacted on February 13th 2012, Turkey was one of the crossroads for donors and recipients from all over the world (Cohen: 2013; Scheper-Hughes: 2000, p. 194). After the strict implementation of the legislation and penalties, global demand on kidneys headed towards other countries where they could gain place.

Allocation system is another component of the regulations. The allocation system must be trustworthy so that people can sign into the waiting list. If the recipients do not have faith in the justice of allocation, they could try to find suitable donors in the black market. After organ transplantation became available, the U.S. and European countries implemented the right and proper allocation systems with legislations.

It is obvious that some patients are not wait-listed recipients. For example, the Turkish government pays minimum wage to the retired patients. When a public servant is stricken by a kidney failure and is given a fully-signed report, s/he gets “retired”. Also, social insurance covers all disease related payments such as HD, hospital expenses and even transportation. If the recipient is a patient in-need of nursing, the system pays the nursing expenses as well. If the patient is not registered to the social security system but s/he needs such care, government would also pay nursing expenses.

On the other hand, when the patient is cured by transplantation, s/he is not considered as a nursing-needed patient. The “nurse” generally has an affinity with the patient and the

18 http://www.x-rates.com/average/?from=JPYandto=USDandamount=1andyear=2011

payment would no longer be available, in other words the nurse would lose the salary. At this point, some patients prefer to suffer until they die rather than being transplanted. A considerable amount of patients are older than 60 years old.19 Since they are waiting for “death” to come soon, they consider it is useless to get transplanted instead of losing the salary.

The effect of legal regulations can easily be observed from the Iranian system. There is no queue and no waiting list in Iran. After the implementation of the legal regulation about selling kidneys freely, the demand decreased rapidly and waiting list melted down (See Section 5.4.1.1).

6.4. Effect of Monetary Incentives on Supply and Demand

Improvements in surgical methods, treatment of pre/post-operative complications and effective immunosuppressives made transplantation an efficacious treatment for ESRD (Ghods and Savaj: 2006). Such advancements made the kidney disease a curable failure and the patients became able to return to their daily lives instead of waiting to die in misery and pain. In Europe, prevalence of ESRD is nearly 1000 pmp (CEU: 2007) however only 20 to 30 percent are accepted into the transplant waiting list. Many others are unable to receive lifesaving treatment (Omar et al.: 2010).

Although various methods are employed for expanding the pool of eligible donors (e.g. lower quality kidneys, acceptance of non-relatives as living donor, creation of organ procurement initiatives) there still is an unstoppable kidney shortage. WHO has been trying to legislate and organize organ transplantation since 1985 (WHO: 1994) and published reports regarding the guiding principles on human cell, tissue and organ transplantation where the recent one was endorsed during the sixty-third World Health Assembly in May, 2010. All of these reports postulate that the organs could only be donated freely under circumstances where there is a monetary payment or reward of monetary value involved. Purchasing or offering the purchase of cells, tissues or organs for transplantation, sale by living persons, by means of any name, should be banned according to Guiding Principle 5 (WHO: 2010).

19 The diversification with respect to age on each year can be monitored from the “Turkish Nephrology Organization” webpage, annual registries. 68

Despite the legal regulations, penalties and bans there is an ongoing and increasing debate about the monetary incentive on organ donation. Most of the researchers and academicians (Freidman: 2006; Evans: 2003; Daar: 2006 and others) stand up for payments or monetary incentives in different ways.

According to these researchers, a monetary incentive is the most effective and applicable means of increasing the supply for kidneys. Evans made a statistical estimation with a survey including different financial incentives (Evans: 2003). Daar concludes that if buying and selling organs is unstoppable as it appears to be, unregulated market causes more harm than benefit (Daar: 2006). Bilgel and Galle made a comparative case study of financial incentives for kidney donation and found out that the passage of tax incentive legislation increases living unrelated kidney donation rates by 52 percent in New York (Bilgel and Galle: 2015).

Monetary incentive does not mean a payment in exchange for a kidney. It is considered as an expression of gratitude to the donor, since it is a “gift of life”. The first Federal Legislative Act was titled as the Uniform Anatomical Gift Act in 1968 in the U.S. The term “gift” stands for the complex notions of generosity, altruism and selflessness (Joralemon: 1995, p. 343).

There is an unmet organ demand in the world. Payment to donor could shift this demand to the suppliers who are convinced with sufficient payment. In China, there was an organization recovering organs from criminals sentenced to death until 2008. A free market was legal in India until 1994. Although a law was enacted in 1994, it did not bring any changes to the existing system. In Africa, missionaries have witnessed the disappearance of people and found organs in communal graves. All these routes reduce the waiting list in all countries and lessen the demand in the market (Novelli et al.: 2007).

Despite the ethical discussions regarding payment for a kidney, payment makes a crucial effect on the supply. The quantity of this incentive is not very important. In every price range, there will be some people who would be willing to donate. It is not an actual sales action since there is not an organized market and a standardized price. The next chapter discusses the fact that no matter there are authorities regulating the markets, there would always be a black market in order to satisfy demand.

Although monetary incentive is restricted in all countries except Iran, it is somehow in action in various forms. The black market is the most common and most known among these. Besides, there are some other ways such as tricking the authorities. Since the authorities ask for proof about the relations and kinship of unrelated donors, some try to find ways to falsify the system and forge documents as proof of kinship.

Benefits of Compensation on Organ Donation

An effective compensated organ donation system will decrease the demand from the black market (Omar et al.: 2010). In case of finding a kidney through legal channels is available, recipients would not seek illegal alternatives. Large family members relatively have a greater chance of finding a living donor. The size of the family and relationship with the members affect the probability of a proper and matching donor (Giles: 2005). It is a disadvantage for people who do not have this kind of relationships. Compensated organ donation would reduce and overcome this inequality for those who lack a related donor.

A member of a group or a society can find a living donor even if there is not an incentive on organ donation. So, monetary incentive would increase the supply with some organizations like websites in the internet. These types of organizations can decrease the inequalities for those who cannot compete in soliciting organs (Omar et al.: 2010).

Compensation can clearly decrease the dependence on dialysis that will result in cost saving and increase the quality of life. Matas and Schintzler calculated an estimate break- even point to be approximately USD 95,000 payable to the potential donor without increasing the overall health expenditures in the treatment of ESRD. Even adding the quality adjusted life years (QALY) for the transplant recipients, a payment up to USD 250,000 to each potential donor would still be cost-effective (Matas and Schintzler: 2004).

Increase in quality of life is another gain for transplant patients. They would have a second chance for a normal life, a possibility of getting into the society again and re-discover their former livelihood. The patients would no longer be losing many hours at dialysis centers and more hours coping with the side effects of the treatment (Fisher et al.: 1998).

7. KIDNEY BLACK MARKET AND TRANSPLANT TOURISM

Crimes are classified according to the nature of activity and the harm they cause. In general there are two main types: (i) trafficking in human, narcotics, gambling, prostitution and (ii) blackmailing and hijacking. The first one is based on the supply and demand consent, the second involves threat, coercion and/or violence (Fijnaut: 2001). Organ trafficking can be put into first category because it is based on the consent of donors and recipients. Besides, it involves illegal goods that are traded by well-organized networks and profit-oriented criminal groups. It also corrupts some certain authorities in order to transport and transplant donors (Vermot-Mangold, Council of Europe: 2003, p. 883).

The crime can be considered as white-collar crime. The whole traffic and trade are mainly executed by organized criminal groups, however a small yet the most important part is operated by a white-collar team (Meyer: 2006). It is not the field of trafficking; it is the transplant procedure they execute. Organ trafficking is an organized crime just like illegal drug trade and trafficking in arms or women. There is no internationally accepted definition of organized crime but a simple and common definition is as follows: ”organized crime ensues when groups primarily focused on illegal profits systematically commit crimes that adversely affect society and are capable of effectively shielding their activities, in particular by being willing to use physical violence or eliminate individuals by way of corruption” (Fijnaut et al., 1998: 26-7).

Bovenkerk defined the criteria for organized crime as criminals that are operating in the underground economy and using criminal methods to make money (Bovenkerk: 1998). In organ trafficking, organs are transplanted in private hospitals, medical records are not taken and transplantations are made at nights (Vermot-Mangold: 2004). It is hardly possible to have reliable data under such circumstances (WHO: 2004) where the main problem is to have scientifically documented and reliable data that are rare in the field of organized crime. Many countries are aware of the crime but it is hard to prove (Council of Europe: 2003). Since it is not widely expanded, it is not that easily visible. Transplant operation is a semi-legal business i.e. it is performed in a private hospital, usually at night

time, in developing countries where legislations prohibiting the selling and purchasing of organs are not in force (Vermot-Mangold: 2004).

Commercialization of a kidney in the black-market appears to be on voluntary basis and mutually beneficial: the donor receives income and the patient potentially regains his/her health. However the results are far from these advantages. Paid donors often face physical and mental health problems (Efrat: 2013). Even under the best social and medical conditions living kidney donors die after surgical operations. When buyers and sellers are unrelated the usual risks multiply; since sellers are generally from an extremely poor class, they are most often very poor in health. Kidney sellers subsequently experience chronic pain, ill health, unemployment, low incomes, serious depression, sense of worthlessness, family problems and social isolation (Scheper-Hughes: 2003). A research in 2002 revealed that the health of 86% of Indian organ donors underwent a significant decline within three years after surgery. Organ Watch reported that 79% of Moldovan donors had health problems after their procedures (Glaser: 2005).

Most illegally donated and transplanted organs come from people living in poverty. Thus, the main donor countries have low socio-economic levels with high unemployment rates (Tomiuc: 2003). In the trade business, desperate people who need money to cover living expenses are on one extreme whereas desperate people who need an organ donor in order to guarantee their survival are on the other. The success of the crime is based on deprivation people from each extreme – either financial or medical (Meyer: 2006).

Countries associated with organ trafficking in Europe are Moldova, Ukraine and Turkey (Tomiuc: 2003) and Bulgaria, Georgia, Romania and Russia are mainly on the organ supply side (Council of Europe: 2003). In general, citizens from Belgium, Croatia, France and the U.K. comprise the main buyers to receive a transplant from the black-market (Meyer: 2006). Nancy Scheper-Hughes, author of several articles and a book about global organ trafficking (Commodifying Bodies, Nancy Scheper-Hughes, 2002), traced organ traffickers in different countries by launching an NGO called Organs Watch in 1999. It is a medical human rights group that monitors organ-trade with social justice concerns in the organ market. It brings into attention the hunger of medical and biotechnology industries about almost all parts of the human body for serving global market capitalism. This NGO traced donated organs from all over the world. Most of the donated organs were from poor countries like South Africa and they were sold to buyers in developed countries like 72

Germany, the U.S. and Austria. Urban hospitals where the poor African-Americans are living are the suppliers of human organs in the U.S.

Organ Watch tracked down the transplant patients and found that organ theft was a common occurrence in the “kidney belt” which covers Brazil, India, Iraq, Moldova and the Philippines. It is not a coincidence that the citizens of these countries are very poor in average and desperate people are willing to sell a kidney for a song; that is almost for nothing. In Brazil presumed consent regime gives right to surgeons to recover organs as much as they can. In Argentina, organ trafficking is targeting people with mental disorders or who are mentally disabled those in the meantime are considered as a burden for their families.

The growing demand triggers transplant tourism. Some of the American hospitals like University of Maryland Medical Center advertise the kidney transplant program in Arabic, Chinese and Japanese on their websites. Israel is a different and unique case in transplant tourism. An experiment program was established to monitor and select purely altruistic living and unrelated donors in Israel. It resulted that almost 2 or 3 of every 40 approved applications were “purely altruistic”. Israeli market operates in one direction: an Israeli is only a buyer and no organs are sold to the global market from Israel.

Organ Watch researchers reported that many of the living donors in the market had died within 18 months after surgery because of medical, social or psychological complications. The report discloses that these donors were unable to pay for follow-up treatments or necessary medications. Scheper-Hughes pointed out to bioethical arguments. In western countries selling an organ is a “choice” but social and economic inadequacies lead to a “free” and “autonomous choice” of selling an organ (Scheper-Hughes: 2002). Organ Watch organization mapped the routes and international medical and financial connections those brought parties together from three or more countries. They detailed some routes from East to West, Europe to other countries and from the U.S. to the Middle East (Scheper-Hughes: 2003).

Organ trafficking disrespects human rights such as right to life, liberty, security and freedom (Glaser: 2005). The annual value of the global organ trade is less than $1 billion (Schimanozo: 2007). WHO estimates that 5 to 10 percent of kidney transplants are

performed through organ trafficking annually around the world (Budiani-Saberi and Delmonico: 2008).

In 2008 a meeting was held in Istanbul about organ trafficking and transplant tourism. The results of this meeting were reported under “The Declaration of Istanbul on Organ Trafficking and Transplant Tourism”. Organ trafficking, transplant commercialism and travel for transplantation were re-defined throughout this meeting and reified by the declaration. The committee declaration proposes “to respond to the need to increase deceased donation, ensure the protection and safety of living donors” and “appropriate recognition for their act while combating transplant tourism, organ trafficking and transplant commercialism”. This declaration could be a guideline for governments to regulate Acts and increase donations.

PART III: TURKEY

8. LEGAL REGULATIONS IN TURKEY

The latest directive was issued on February 1st, 2012 and published in the official gazette (Turkish Ministry of Health: 2012). It is based on the first 2238 numbered regulation that was enacted on March 29th, 1979 which was about Recovery, Preservation, Vaccination and Transplantation of Organ and Tissues (Official Gazette: 1979).

National Coordination Council (NCC) was established by law. Among its several duties, it is authorized to supervise the transplant centers. The centers are established as National Coordination Centers those work 24/7 and book the registry of all patients and organ and tissue wait-listed patients.

Regional Coordination Centers (RCC) are also established by law and are located in 9 different cities which are İstanbul, Ankara, İzmir, Bursa, Antalya, Samsun, Erzurum, Adana and Diyarbakır. Each center is responsible for various other cities within the defined province of the center. RCCs are responsible of coordinating the transportation of recovered kidneys and organs to the center where the recipient is waiting for transplantation. They also handle medical, administrative and legal paperwork of the donor and the recipient. National Coordination System coordinates nationwide allocation and logs and keeps all data of the patients in the Organ and Tissue Reconnaissance System of Turkey.

8.1. Organ and Tissue Allocation Principles

Allocation system has to be transparent and confidential while restricting misuse and favoritism. In order to ensure security, the allocation must be done in an electronic environment. The system should allow enhancement and upgrades even during the process. Allocation must be based on preferred donation (i.e. the organ(s) of a deceased donor shall

be given to his/her kin till 4th blood level including his/her spouse) and family grading system (i.e. giving extra grades to the donor’s kin with 2nd blood level and his/her spouse).

8.2. Donation and Transplantation from Living Donor

Transplantation shall be possible up to his/her 4th blood level kin and/or spouse which are living actually together for at least 2 years. This rule is for the sake of the prevention of exploitation and for the protection of the donation system. Otherwise it may give rise to kidney sales. The system makes donation from unrelated kidney donors possible subject to some very strict rules, which involve an interrogation of the living donor and the recipient by an ethical committee. The decision for transplantation shall be upon the decision of the committee in light of the findings and conclusion it reaches.

8.3. Kidney Allocation Principles Kidney allocation is made according to a waiting list. The patient must be enrolled in this waiting list for kidney transplantation. Every patient is examined, ranked and graded throughout the period of his/her disease. In the case of a deceased donation, the NCC checks the grades and decides on the allocation as per some rules. Among the many, important ones of the mentioned rules are given below.

Kidney allocation is made by NCC in accordance with the matches and grades in the Organ Waiting List. Every recipient shall receive a kidney from the same blood-type donor. If there is no emergency notification and there are zero mismatches, then the following shall apply:

1) If there is a recipient with zero mismatch and same blood-type the kidney shall be transplanted to that recipient. 2) If there are more than one zero-mismatch patients, the kidney will be transplanted to the recipient with the highest grade.

General rules and liabilities for kidney allocation are as follows:

1) Transplantation centers must enroll their patients who are waiting for a kidney donation from a deceased donor in the National Kidney Waiting List.

2) Transplantation centers must take NCC matching and scoring results into consideration while transplanting to their kidney or kidney and pancreas waiting patients. 3) Transplantation centers must register the citizenship ID and name into the NCC before making a transplantation surgery. 4) As long as scores are taken into consideration, patients waiting both for a kidney and a pancreas have priority over those patients waiting for a kidney only. 5) Transplantation centers must remove the living-donor kidney transplant patients from the National Waiting List. 6) If a transplant center refuses an allocated kidney or there is no minimal tissue matching, then the kidney shall be offered to the center with the next highest score. 7) Every patient shall be registered only at one single transplant center. 8) For the calculation of dialysis-entry score, every patient shall give the first dialysis- entry document to his/her registered center and the center shall keep this document. 9) For the calculation of waiting time, first dialysis-entry date shall be taken as the beginning date. If a transplanted kidney would not properly function within the first 6 months, the transplant center shall enroll the patient in the Waiting List again. 10) Transplant center shall determine the tissue type of the patient, report it to the NCC and verify the grading/scoring process. 11) Transplant centers shall check the citizenship ID and data of their patients in the National Organ Waiting List and update them fully, properly and correctly in every 6 months.

In the case of a deceased donor from any existing transplant centers, the following rules shall apply:

1) The transplant center shall verify/determine the tissue type of the deceased donor and register the confirmed tissue type to the NCC. 2) The NCC shall be responsible for the matching and scoring in order to assess the most proper kidney recipient. 3) The NCC shall allocate one of the kidneys of the deceased to the transplant center in concern on the basis of least tissue-match condition. 4) The other kidney of the deceased donor shall be transported to another transplant center on the basis of matching scores.

The NCC employs an evaluation criterion according to which every patient shall be graded. With respect to the region, the patients are graded over 1000 points, accordingly the maximum score the transplantation center of the donor brings shall be 250 points. Every age-scale counts for an extra grade and dialysis time of the patient scores3 points for each month. Allocation is based primarily based on this grading system in addition to the satisfaction of other primary conditions previously mentioned.

9. KIDNEY TRANSPLANTATION AND DONATION IN TURKEY

9.1. Legal Status

Main objective of legal regulations is to organize and regulate the activities within defined criteria. These rules have to ease the activities and protect the rights of the parties. In Turkey, since most of the kidney donations are from living donors, the regulations have to organize and protect the rights of the donors and also avoid possible violations.

Turkey is/was one of the crossroads for transplant tourism, especially for European transplant candidates as mentioned in Chapter 7. The legal authority had to revolve the regulations and in 2012 (Official Gazette No: 28191, publication date: February 1st,2012) commodification of organs was strictly banned and subjected to penalty. Evolution of the rules was based on the first Act.

These regulations focused on the abuse of the living donor and distribution of the donated kidneys (organs). Although living donations are encouraged, unrelated living donors are subject to an in-depth questioning by a committee (i.e. Ethical Committee for Evaluating the Application of Organ Transplantation Unrelated Persons that is provincial in City Health Directorate). Living unrelated donations are wide open to abuse. Committee members have to be convinced that living unrelated donors are donating their kidneys voluntarily. The committee applies the Act however their decision is open to debate. There are some cases under adjudication those refuse the judgment of the committee20.

20 One of the most remarkable decision was made by the 5th and 6th Administrative Courts of İstanbul. A patient had sued the decision of the committee about the rejection of liver donation from an unrelated donor. The justification of committee reads as follows: “There is no opinion that there is no ethical and illegal situation between the buyer and the donor”. However the reason about the cancellation of the committee’s justification by court says: “the decision is not based on written and concrete information”. For further information see the website http://www.hurriyet.com.tr/mahkemenin-3-sahislardan-organ-nakli-kararina- tipcilardan-itiraz-40032756 79

One of the main objectives of the regulations is about Organ and Tissue Transplant Services which was updated in February 201221. This Act focuses on the distribution of organs and coordinating RCCs. The regulations impose penalties however the level of deterrence is not high enough since it suffers from a deficiency of critical issues. In the revised version of the Organ and Tissue Collection, Storage and Transportation Act on January 12th, 2005, Article No: 14 states; “If the person died because of an accident or a natural disaster and does not have any relatives (spouse, adult children, father, mother, sister, brother or any next of kin), his/her organs can be transplanted to the persons whose lives are dependent on organ and tissue transplant without a consent or a testament”.

The legal regulations are arranged by the 5237 numbered law, put into effect on September 26th, 2004 and related legislative regulations are Turkish Penal Code 91, 92 and 93. These Codes include 5 main subtitles: 1) transplanting organ and/or tissue from a living person, 2) transplanting organ and/or tissue from a deceased one, 3) buying, selling and/or mediate buying of organ and/or tissue, 4) collection storage and transportation of organ and/or tissue, 5) advertisement and announcement for supplying an organ or a tissue. The mentioned subtitles are examined in the following paragraphs.

1) Organ and/or tissue from a living person: In TPC (TCK) No: 91/1 the judgment is: “Any person who removes an organ from another person without his lawful consent shall be sentenced to a penalty of imprisonment for a term of five to nine years. If the subject of the offence is tissue, then the offender shall be sentenced to a penalty of imprisonment for a term of two to five years” (Venice Commission: 2004). In accordance to law no. 2238 in article 6, valid consent is defined as: “The person must have completed 18 years of age and has to have power of discernment. For grafting an organ or tissue, a previously written statement signed by the donor in the presence of two witnesses, or a statement signed after verbal expression in the presence of two witnesses , consciously and with free will shall be approved by a physician ”

The law imposes obligations to the surgeons and physicians those who graft organs and tissues. Article 7 of the law regulates the attitude of the surgeons about informing the donor and/or his/her next of kin and the eligible persons who are potential donors:

21http://www.mevzuat.gov.tr/Metin.Aspx?MevzuatKod=7.5.15860andMevzuatIliski=0andsourceXmlSearch= organ%20ve%20doku%20nakli 80

“Doctors who will graft organs and tissues shall:

a) Explain exactly and clearly the medical, psychological, familial and social consequences of grafting an organ or a tissue to the donor; b) Inform the donor about the benefits of the recipient; c) Deny grafting organ or tissue of a person who is not mentally eligible or not in the right frame of mind to decide; d) If the donor is married, search that if his/her spouse is even informed and must officially report the information; e) Reject grafting an organ that donates in return of money or any other profit or donation out of humane purposes; f) Not disclose the name of donor and recipient except for affinity by marriage or kinship”.

2) Transplanting an organ or a tissue from a deceased one: According to TPC, No: 91/2: “Any person who unlawfully removes an organ or tissue from a deceased person shall be sentenced to a penalty of imprisonment for a term of up to one year.”

Grafting an organ or a tissue unlawfully is defined as a crime by the law because of the violation of the personal rights of the next of kin. However, there are some exceptions where permission for the next of kin is not required. According to Law No: 2238 Article 14/4, “If the deceased body is heavily damaged after an accident or a natural disaster, organs and tissues can be removed without next of kin’s permission in the case of absence of the relatives and under medical necessity and urgency. If the relatives are present, their permission shall be taken”. According to Article 14/1, organs of any person shall be recovered upon the consent of the his/her spouse, family member or relatives subject to official reporting it the person did not officially declare donation in the face of two witnesses before his death. On the other hand, unless otherwise stated, some tissues which do not affect the integrity of the body, like cornea, can be taken without permission (Law No. 2238 Article 14/2).

3) Buying, selling and/or mediate buying of organ or tissue: According to TPC, Article 91/3: “Any person who purchases, or sells, an organ or tissue, or acts as an intermediary in such activities, shall be sentenced to the penalty in 91/1.” In other

words, either from deceased or living, any organ or tissue-trade is forbidden no matter either it is removed according to the rules or not. The main importance is about “selling” an organ or a tissue. Mediating the transaction is enough for the commitment of crime (Meran N.: 2008). In the act of buying or selling an organ, the consent of the donor is not important and is out of concern. Even if the organ is grafted within the definition of the rules, the crime already exists (Şen E.: 2006). “Where a person, who sells his own organ or tissue, informs the relevant authority of such before such activity is identified by the relevant authority and assists in the arrest of the offender, no penalty shall be imposed” (TPC, No: 93). If it is an organized crime, it will be an aggravating circumstance. 4) Storing, transporting and implementation of organ and/or tissue: The penalty is defined in TPC Article 91/5: “Any person, who conceals, transports or engages in the transplantation of an unlawfully obtained organ or tissue, shall be sentenced to a penalty of imprisonment for a term of two to five years”.” According to the law, each one of action is separately treated as a crime. In this article, the victim is the one whose organ or tissue is removed. The victim must be a living person. In case the victim does not survive and has no heir, the state shall be the heir (Arslan, Azizoğlu: 2004). If the organ is transplanted or tissue is vaccinated by an unauthorized entity, it shall also be considered as a crime. Anyone who helps in organ or tissue transportation shall be penalized as a criminal. There are no aggravating or extenuating circumstances. 5) Making advertisement and announcement for supplying an organ or a tissue: The provision of TPC Article 91/6 is this: “Any person who broadcasts, makes an announcement, or engages in commercial advertising in order to secure organs or tissue in order to obtain any gain shall be sentenced to a penalty of imprisonment for a term of up to one year.” According to this Article, announcing, advertising or publishing are all considered as a crime individually. The main purpose is to prevent and stop organ-trading from the very early stages of the crime (Şen: 2006). Internet ads are classified within this context. Publishing an ad is considered evidence for the commitment of the crime in this category.

As the articles of the law indicate, the only activity making such legal is saving life and healing people. On the other hand, article 92 of TPC, the law suffers from a very critical

deficiency which actually helps understanding the basics of how to commit this “crime” without being subject to a penalty. Article 92 reads as follows: A penalty may be reduced (or not imposed at all), after considering the social and economic conditions of the person selling his own organs or tissue. Under normal circumstances, no one would be selling his/her organ(s). It is obvious that any seller has to be very desperate so as to sell his/her organ(s). In fact, that is why organ black market is generally based in poor countries and targets poor people. Therefore, it is almost impossible to punish someone by law.

As a matter of fact there are some other deficiencies from which the law suffers such as regulations on auto-grafting, transplantation of ovary, protecting and using stem cells etc. (Aydın: 2011). However this issue is beyond the scope of this thesis.

9.2. Change in the Last Decade

The incidence of ESRD is increasing in the World (White et al.: 2008) however researches show that the awareness about the kidney disease is not more than 10% even at the stage between 2 and 422 (Plantinga LC et al.: 2008). Early disease recognition could help prevent or delay the disease. Results of the Kidney Health Bus Project run by the Turkish Nephrology Association (TNA) in 2010 in 21 different cities of Turkey revealed that the public awareness of disease was about 5.7% (Turkish Ministry of Health: 2014, p. 17). Actually, chronic kidney disease is generally asymptomatic in early and middle stages and it is not easy to consider incidence and prevalence without community based works (Turkish Ministry of Health: 2014, p. 21).

Diagnosis of the disease is an everlasting and costly period. The patient has to be monitored for at least three months. The amount of urine must be regularly measured throughout this period. Unfortunately there is no organized scoring for the number of kidney patients in the recent years. Annual registries of the TNA report average numbers for peritoneal dialysis (PD) and hemodialysis (HD) patients and transplants. The Ministry of Health is publishing the number of donors, patients and transplant patients since 2011. On the other hand, these figures do not match with registries of the TNA registries. However formal reports such as European Dialysis and Transplant Association-European Renal Association (EDTA-ETA) registries use TNA registries at all.

22 For stages of kidney disease, review Chapter 3, Section2 83

Yearly progress of kidney donation, kidney patients and renal transplants in Turkey are available on the website of the Ministry of Health. According to the formal information, the data is as follows;

Table 10: Transplantation quantities from living and deceased donors (2011-2015) Source: https://organ.saglik.gov.tr/

Donor Living Deceased Total

2011 2831 333 3164

2012 3471 345 3816

2013 3370 379 3749

2014 3244 407 3651

2015 3447 472 3919

The figures in the table indicate to a 21.75% increase in living kidney donation between 2011 and 2015. It is obvious that promotions and advertisements have been effective in this period. The week between 3rd and 9th of November is declared as Organ Donation Week every year and every provincial health directorate attends the activities throughout this week. The program that is held by Turkish Public Health Organization, Kidney Disease Prevention and Control Program is effective on increasing awareness of renal disease promotes kidney donation. There is a 41.75% increase in deceased donors. Percentagewise, this increase is fascinating however it is much too lower when compared to other European countries.

The next graph illustrates the change in the number of people on the waiting list which is increasing in time. There is a 24.5% increase in waiting list patients and the total waiting list patients are 22,385. While increase in donation rates is slightly less than the increase rate of wait-listed patients, it is not sufficient to meet the demand and close the gap between the donors and recipients; therefore the gap keeps growing.

patients added in waiting list (yearly)

8000 7000 6000 5000 4000 added patients in waiting list 3000 2000 1000 0 2011 2012 2013 2014 2015

Figure 13: The quantity of patients added to the waiting list (yearly basis) Source: https://organ.saglik.gov.tr/

There is a remarkable increase in the amount of kidney transplantation however not adequate. Quality of the transplantation teams and hospitals are capable and sufficient enough to meet the demand in Turkey. On the other hand, Turkey is one of the main transplantation crossroads for kidney black market (Meyer: 2006, p. 216). These transplant centers perform surgeries under illegal circumstances. There is no data regarding the activities of this market, and the figures cannot be determined. According to WHO, almost 10% of the transplants are performed under illegal circumstances (Budiani-Saberi et al.: 2008).

The number of transplantations in Turkey is increasing every year. From 2007 to 2012, the figures were doubled. This is explained by increase in awareness, the quality of surgeries, success of the operations and medical conditions. Bu the striking part is about the living related donations. Majority of these donors are of next of kin which is attributed to strong ties of kinship.

4500

4000

3500

3000

2500 Living Donor 2000 Deceased Donor

1500 Total Transplantation

1000

500

Figure 14: The transplantation data and the graph of Turkey Source: Türk Nefroloji Derneği (2015)

9.3. Fundamentals of Selection Process and Urgency of Transplant Patients in General

Increasing number of recipients on the waiting list for kidney transplantation is an increasing problem worldwide. Transplantation is the most appropriate option for ESRD failure (Kaçar et al.: 2013). Organ supply is an important problem while number of patients on the waiting list is ever-increasing (Shrestra: 2009). In a study from Chile that investigated the effects of different kidney exchange mechanisms found that if all the patients on the waiting list had a willing direct donor, 47.7% of patients would receive a transplant (Dominguez et al.: 2011).

Being enrolled in the waiting list has some consequences; (i) patients will have increased risk of death, (ii) there will be reduction in quality of life, (iii) increased risks for developing other diseases and finally (iv) there is a potential to become ineligible to receive a kidney (Herold: 2008, p. 12)

At this point, selection of the perfect patient for donated organ is important. However there are some conditions that must be satisfied by the patient. In general these conditions can be listed as:

. Not having severe liver, lung or heart failure, . Not having current cancer therapies, . Being able to understand and manage the medical treatments, . Not to be severely obese, . Not to smoke (some transplant centers refuse to make transplantation unless the patient quits smoking at least 6 months before the operation), . Having an adequate insurance to cover the transplantation and medication costs.

(UW Medicine, Harborview Medical Center)

There are some contraindications for selecting or refusing the kidney donor. A brain-death diagnosis is required in a comatose patient who may be a potential deceased donor. The potential donor must be examined for any pathological condition and the quality of organs being considered for transplantation. A short ischemia time is required to reduce the possibility of the rejection of the usable organ. The potential donor must be examined in terms of the following infectious diseases (Kalble et al.: 2014, pp. 18-19):

 Human immunodeficiency virus-1, -2 (HIV-1, HIV-2)  Hepatis C (HCV)  Hepatitis B surface antigen (HBsAg), anti-HBc; acute hepatitis (liver enzymes)  Cytomegalovirus (CMV)  Epstein-Barr virus (EBV), only in pediatric recipients  Active syphilis  Viral infection, sepsis, tuberculosis, infections of unknown aetiology  Family history of (or clinical signs those may be caused by) Creutzfeldt-Jacob disease

There are some certain contraindications those make a donor unsuitable for transplant; active cancer or a history of metastatic cancer. Below, some vascular conditions which are the factors for excluding potential donors are given:

 Previous myocardial infarction  Coronary bypass and angina  Severe systemic vascular disease  Events of long-lasting hypotension

 Oliguria  Long-lasting intensive care stay.

Selection or refusing criteria for the recipient is similar with the donor however there are some differences which are as follows (Kalble et al.:2014, pp. 31-35):

 Malignancy: active malignancy is a problem because immunosuppressive drugs can increase the malignancy,  Infection: infections are the main factor for morbidity and mortality in transplanted patients because of the immunosuppresives,  Other contraindications: scarcity of organs, complexity of transplant procedure, psychological conditions,  Comorbidity: especially cardiac disease, peripheral artery disease, cerebral occlusive vascular disease,  Diabetes mellitus: patients with diabetes have an increased mortality and reduced long-term graft survival compared to non-diabetic patients (Wolfe et al.: 1999),  Obesity: overweight patients have higher incidence of surgical and non-surgical complications such as diabetes, hypertension and cardiovascular disease (Gore et al.: 2006),  Coagulopathies: has a negative impact on post-transplant graft survival,  Other diseases with potential influence on post-transplant outcome,  Age: patients over 65 years old have mortality risk in transplant patients compared to those below 65 years old in the waiting list (Merion et al.: 2005),  Recurrence risk: high recurrence risk can lead to an immediate graft loss.

These contraindications are general rules and other specific examinations could affect the selection process. The allocation principles are another issue that is explained in Chapter 8.

10. COST ANALYSIS

10.1. Cost of Dialysis in Turkey

This section gives a summary about legal Regulations on Dialysis Centers and analyses the factors those affect costs. A practical case from Atatürk Research Hospital will be examined which is the research and application hospital of Yıldırım Beyazıt University. This example examines every stage and application of dialysis. A cost analysis of hemodialysis centers is given studied by TNA which diversifies each component of the costs of dialysis. Finally, problems and practical solutions of dialysis centers are discussed. The literature about the costs of dialysis is given in Section 10.5.

There are some common rules which are regulated by the government. The “Regulation on Dialysis Centers” was published in the Official Gazette issue number 27615 June 18th, 2010. Every center (private or public) is obliged to strictly act in accordance with the regulation throughout HD treatment. Every patient diagnosed with chronic renal failure and dependent on dialysis can receive treatment from any center certified according to “Regulations on Dialysis Centers” and has a contract with Ministry of Health. These treatments have to be in line with the principles and procedures of the Health Notification Application (SUT). Each patient must have a report that has to be written by a specialist physician. The prescriptions can be written by the physicians working in these centers. In case there are differences in the number of sessions, reports must be re-arranged. Every session must be at least 4 hours (except for medical necessities). All the costs are included in the payment of governmental social insurance (TRY 172.8 per session for 2016).

There are many factors affecting the costs which are: (i) operation team labor costs, (ii) medical material and drug/serum costs, (iii) audit expenses before and after the analysis, (iv) direct material and labor costs, (v) equipment depreciation costs, (vi) equipment maintenance costs, (vii) transportation and fuel costs and (viii) cost of dilution solution used in dialysis water (Tatar: 2015).

The analysis of the calculation of each cost is given in Appendix 3. For example, there are 44 different test and analysis items, 4 different drugs and serums, 5 different medical equipment and 5 different staffs each including one dialysis doctor, one nephrologist, one

psychiatric and one psychologist. Each dialysis machine has a 10-year economic life and usages of these machines are different from each other in terms of patients, staffs and session times. Each machine has a maintenance costs and depreciation. Besides, these are the routine costs for each machine and patient. Each patient must be transported as per the regulation. On the other hand, if the patient comes to the hospital in case of an emergency, costs arise because there are some other factors that affect the preparation of patient for dialysis.

There are some other components those affect the costs The number of machines is a primary factor. According to the regulation, there must be at least 10 machines. This study primarily comprises data taken from Atatürk Application and Research Hospital owing to the fact that the hospital mentioned is actually linked to Yıldırım Beyazıt University. There are 25 dialysis machines in this hospital and the patients are attending 2 or 3 sessions every week. Working hours are between 8:00 AM and 5:30 PM and the doctors make the rounds in the mornings and at noon periodically, and evaluate the test results. The nurses are present during the sessions. The first dialysis of a patient takes 2 hours;, the second dialysis takes 3 hours and further sessions take 4 hours. There is a standard dialysis kit used for each patient and dialysis water is periodically tested every 3 months. Outpatient treatment patients are transported by shuttles and each shuttle is priced on per km basis plus value- added tax (VAT). The inpatients attend dialysis sessions throughout their inpatient period. The center serves the chronic and acute patients those contact under emergency. Intensive care patients are dialyzed as long as they need and dialysis nurses serve these patients. Training is provided for each patient and called for discipline during their treatments. For chronic patients; biochemistry-blood count tests must be repeated every month, crp- hormone-serology tests in every 3 months, usg-lung grapy and check-up are again repeated every month. These patients are also examined by a psychiatrist and psychologist on a monthly basis.

Each of these items mentioned would increase the cost of HD. For the calculation of the total cost, each cost is considered separately based on the patient and each session. The cost of an emergency patient, a chronic patient, an intensive care patient, a monthly, a 3 or 6-month patient are different. In fact, costs vary depending on the patient and duration. The economic analysis for each one and each period is given in Appendix 3.

A detailed and extended analysis is made by Tatar (Tatar: 2015) regarding privately held hemodialysis centers which are associates of the TNA. Tatar analyzes the data, gathered from every TNA member, and with respect to total expenditures, total patients, total number of machines, total sessions, average unit cost per patient, average unit cost per machine and average unit cost per session and ends up with an average unit cost per session of TRY 175.9 in 2013 and TRY 177.6 in 2014. There is a dramatic decrease in the government payments made to the HD centers and it appears that in general they close the fiscal year with annual net loss.

At this point it is a matter of question why the centers keep on their services and how come the business survives. The answer to this is almost devastating. Although it appears that the centers are in net loss, it comes out that they find it expedient as long as they are able to commit frauds. Some centers forge documents as if a session is attended by a patient although it is not actually made and share the payment with a fake attendee (also a patient). Some patients are eager since they are paid for nothing. On the other hand, some of the patients are so poor that they (can) easily leave their health aside for this extra money. Another form of a fraud committed is abridging durations of dialysis sessions, such as running a session for 2 hours or even less which is supposed to be 3 or 4 hours in actual. The math is simple; extra patient(s) for each machine in regular working hours mean(s) (an) extra session(s) which in turn mean(s) extra income for the center. Such patients again are among those tired of life and exhausted so as to give up their lives.

10.2. Cost of Transplantation in Turkey

In the preceding section cost of hemodialysis is calculated utilizing the data taken from Atatürk Education and Research Hospital. Instead of anonymous and general information, the data of the same hospital will be used for calculating the cost of transplantation. Literature about the analysis of transplantation and dialysis costs in the world are given in the following section.

Calculation of transplantation costs is more complex than calculation of HD costs. In HD cost calculations diagnosis costs of the patient together with other costs like depreciation and maintenance were considered.

When it comes to calculating the transplantation expenditures different items are considered in the data set. First of all, the tests and polyclinic evaluation is important for the donor. There are three doctors (a nephrology specialist, a radiology specialist and a radiology technician) for outpatient visit. Since the physicians decide on the surgery (this decision involves some additional diagnostic tests) there will be another team for preparing the donor to surgery. At this point there will be a team of 6 persons; a general surgeon, an endocrinology surgeon, a cardiology surgeon, an assistant doctor, a nurse and an anesthetist.

During the surgery, the number in the team increases; a professor, an associate professor, a specialist doctor and an assistant doctor as general surgeon, an anesthetist specialist and his/her assistant with a technician and a nurse; a total of 8 persons. After the surgery, 5 of them will still be in charge and an endocrinologist joins the team. So there will be at least 10 different specialists who will be in charge for an operation.

58 different medical equipment are used for a patient. Health Notification Application Code and cost of each equipment are given in Appendix 3. Although the materials and length of stay will differ according to the donor and patient, the analysis is based on a healthy donor. There were 29 different drugs and serums involved some of which are immunosuppressives and are highly expensive. There are also 53 different tests and examinations throughout the process.

Since the analysis is based on the cost of living donor, there are some tests required repeatedly until the time of surgery. Similar tests (even more) are required for the patient as well. Same number of staff will be in charge and much more medical equipment will be needed for the patient. According to the data utilized in this thesis, 204 different service and tests were made on a recipient, 47 different drugs were given and 20 different consumables were used. Total costs for these materials amount to TRY 8,895.2. The general data are given in the Appendix 3whereas detailed data can be provided upon request.

Actually the mentioned materials and costs would differ depending on the co-morbidities of the patient which would require additional costs. There are some possible diseases those can emerge in relation to a kidney disease such as cardiovascular disease, diabetes

mellitus, stroke etc. (Wong et al.: 2012) or the patient can be an Intensive Care Unit (ICU) patient. Such factors would also affect the costs of the surgery.

The cost of transplantation differs accordingly whether the donor is a deceased or a living donor. Although some of the tests would not be required for a deceased donor, there is a shortage in terms of time and the therefore surgery team has to take immediate action in order to avoid the effects of deterioration. The recommended maximum duration before transplantation is 72 hours for a kidney provided cold ischemia (KDİGO) is involved.

The cost of living donor is between TRY 36,358.50 (USD 12,44423) and 38,319.89 (USD 13,115.5) including service costs between TRY 5,103.82 (USD 1,747) and 8,531.63 (USD 2,920). On the other hand, the cost for a transplant recipient varies between TRY 42,156.03 (USD 14,428) and 52,942.13 (USD 18,120) which includes service costs between TRY 8,985.23 (USD 3,075) and 30,750.61 (USD 10,524)24. The Ministry of Health employs a “Health Applications Notification” (HAN) where the costs are built and priced by their codes. The Ministry assigns a code for every operation/drug/material and service which has a multiplier that is updated every year. The parties involved, calculate their receipts by using these codes. The code of kidney transplantation is 618.610 and the corresponding process point is 2,639.12 (HAN; SUT 2-C). Using this code, the standard payment of Social Insurance Institution which is TRY 33,480 (USD 11,459) for kidney transplantation could be found on the Medical Process (Test-Examination-Treatment) Search Screen25. The same calculation could be made for HD and home-HD. Their respective codes are 704.230 and 704.233 and the payment for both is TRY 178.08 (USD 61.2) for 2015.

10.3. Comparison between Transplantation and Dialysis Costs

Health issues are expensive in general on the basis of diagnosis, medication and treatment. Some illnesses require a short period for treatment while some require longer times, besides some diseases do not have an exact treatment like cancer, aids etc. Kidney shortage is among those kind of diseases and there is no absolute solution; however the patient can

23 http://www.x-rates.com/average/?from=TRY&to=USD&amount=1&year=2015 24 These are the exact costs that are derived from actual data of operations performed in Atatürk Education and Research Hospital. These data are utilized with the permission given by the Ethical Committee. 25 https://gss.sgk.gov.tr/OzelSHSBilgi/pages/tibbiIslemArama.faces

survive for some more time via dialysis as a person never able to fully recover and get healthy. The only cure for ESRD is having a kidney transplantation. Yet dialysis sessions are costly, while they are painful for the patient as well. This bill is paid either by the government or an insurance system; however the expenditures increase in time and it won’t be lower unless the recipient is transplanted. Transplantation is costly either but cumulative costs are lower when compared to dialysis costs for one single year.

The following paragraphs give the costs of HD and Tx in various countries taken from some articles. Sanchez-Escuredo at al. made an extensive cost analysis of HD and Tx in 2015 for Spain (Sanchez-Escuredo et al.: 2015). They conclude that the annual cost of HD is €43,000, cost of living-donor in Tx is €8,128 ± 854 and cost of recipient is €21,769 ± 4,866. In total, the cost of Tx is €29,898 ± 5,720. Another cost-analysis of HS in Spain was €40,136 in 2011 (Parra Moncasi et al.: 2011). It is obvious that the cost of Tx is lower than cost of HD. Villa and his colleagues made and extension analysis of the costs of HD, peritoneal dialysis and Tx based on prevalence and incidence patients. They found that the cost of HD is €37,968, PD is €25,826 and Tx is €38,313 (Villa et al.: 2011).

Another HD and Tx analysis by Elsharif et al., for Sudan reveals that every dialysis session is $65.8 and cost per year is $6,847 in 2010. Tx costs in the first year are $14,825 and annual costs of treatment following the first year is $10,652 (Elsharif et al.: 2010). According to Baboolal et al., annual cost of HD and PD in UK is £35,023 and £21,655 respectively (Baboolal et al.: 2008).

Cost-analysis of transplantation and dialysis by Freedland and Shoskes for the U.S. in 1998 shows that dialysis cost per patient is $37,044 and cost of Tx and medicine for first year is $87,598. Medicare in the following years is $8,515 and failed Tx expenditures are $48,870

(Freeland and Shoskes: 1999). In Macedonia, there is a huge gap between HD and Tx costs which are €83,049 and €38,894 respectively (Vacevska et al.: 2006).

Cavallo and his group made a detailed cost-effectiveness analysis for Italy. Their research includes hospital HD, home-HD, satellite dialysis and PD with the complications. Cost of dialysis varies between €21,280 and €37,881where the difference results from nursery and diagnosis expenses. They also analyzed the costs of transplantation from a living donor, from a brain-death donor and from a cardiac-death donor. Cost for receiving kidney from a living donor was €43,366 that includes the surgery cost of the donor and annual follow-up

cost. Follow-up costs are founded as €10,532. Deceased brain-death donor costs is €54,335 with a follow-up costs of €11,551. Deceased cardiac-death donor costs are close to the previous one: €59,502 and €11,632 as follow-up costs for the following years. This article is one of the most detailed Tx versus HD cost-effectiveness analysis (Cavallo et al.: 2014).

Table 11: Costs of HD, PD, Tx from living and deceased donor for countries

Country HD PD Tx (living) Tx (deceased) Year Author Spain €43,000 €29,897±5,719 2015 Escuredo et al. Spain €40,136 2011 Moncasi et al. Spain €37,968 €25,826 €38,313 2011 Villa et al. Sudan $6,846 $14,825 2010 ElSharif et al. UK £35,023 £21,655 2008 Baboolal et al. US $37,044 $87,598 1999 Freedland et al. Macedonia €83,049 €38,894 2006 Vacevska et al. Italy €37,881 €27,435 €43,366 2014 Cavallo et al. Serbia €16,534 €48,949 2008 Perovic et al. Hungary $77,075 $30,293 2001 Kalo et al. Austria €43,600 €25,900 €50,900 €51,000 2011 Haller et al. Germany €30,667 2001 Greiner et al. Iran $11,000 $3,181 X 2 2013 Salamzadeh et al. France €13,601 €20,050 2014 Sainsaulieu et al. Greece €36,247 €30,719 €33,318 €30,109 2008 Kontodimopoulos et al. Palestine $16,085 $16,277 2015 Younis et al. Portugal €28,033 €61,658 2012 Rocha et al.

Source: Author

Another study of a European country, Serbia, by Perovic and Jankovic examines the issue with a 10-year approach which concludes that the cost of HD is €16,534 and Tx from a deceased donor is €48,949. A detailed economic evaluation of kidney Tx and HD is made by Kalo et al., for Hungary. Mean cost of HD for 3 years per patient is $109,197 and mean cost of Tx for 3 years per patient is $70,297 (Kalo et al.: 2001).

Maria Haller and collogues made a cost-effectiveness analysis of kidney transplantation for Austria. Treatment costs of HD for a 12 month-period was €43,600, transplantation cost from a deceased donor for the same period is €51,000 and from living donor is €50,900. They also made an ongoing analysis for 24 months and beyond 25 months (Haller et al.: 2011). Greiner and Obermann made a socio-economic evaluation of kidney transplantation in Germany. They added up examination costs, costs of pre-operation phase, operation, treatment, subsequent operations and found €30,667 on average that the total cost of transplantation varies between €16,899 and €113,431 (Greiner and Obermann: 2001).

Another detailed evaluation made by Kontodimopoulos and Niakas analyzes cost of HD, PD and renal transplant with costs of following years and with different discount rates in Greece. They also discount QALY with different rates. The cost of HD is €36,247 on average that is between €33,126 and €38,070, and €30,909 on average, between €30,530 and €30,719 for PD. The cost of living transplantation from a living donor is €33,318 and €30,109 from a deceased donor (Kontodimopoulos and Niakas: 2008).

Younis et al., made a meta-analysis of the costs of HD, Tx and after-Tx costs for Palestine. They found that the cost of HD on a yearly basis is $16,085 and the cost of Tx is $16,277 for the first year. The follow-up cost of subsequent years is $2,960 after-Tx (Younis et al.: 2015).

Rocha and his colleagues made a profound analysis for Portugal. They found that cost of dialysis is €28,033 per year and cost of Tx was €61,658 for the first year. The calculation includes the follow-up treatments after-Tx as €6,526 for the following years. Break-even point between Tx and HD is 32 months (Rocha et al.: 2012).

A detailed cost-analysis of private dialysis centers made by Tatar for the TNA in 2015 analyzes the average unit-cost for each patient, each machine and average unit cost of each session (Tatar: 2015). Standard cost evaluation for Turkey is possible by using HAN according to which payment for Tx is TRY 33,480 and payment for HD (even for home 97

HD) is TRY 172.8 per session. The process and a brief expression of gathering the data are given in the Appendix 2.

The payment is a fixed package and it does not differ from the need of HD patients. Therefore, dialysis centers look for ways to reduce the use necessary materials down to a level as much as possible. Moreover, private hospitals which perform transplantation surgeries are made a standard payment. It does not matter either the patient has comorbidities or not. Hospitals attempt to 3 ways to increase the bill or the money they receive under informal circumstances. They would demand extra payment from the patient’s next of kin named “the knife payment” which is actually asking for extra money for undertaking the surgery (it is not so easy because if any complaint about the hospital is made to the Health Ministry, there will be a penalty cut), demand extra accommodation costs (not only for the patient but also for the companion’s payment) or generate inflated bills with extra materials that are not used or used but more than needed (this is also hard to do because there will again be a penalty cut in case the bills are controlled and the fraud is revealed). Thus, private hospitals are sensitive in terms of accounting. Searching through the internet forums, various fraudulent applications for almost every hospital would come to attention however it is impossible to prove such or obtain any real and valid data from them.

The list shows that the cost of transplantation is less than the cost of dialysis on a yearly basis (only two of them have a significant difference). After-transplantation medical care costs comprise the main difference. If a patient does not have the transplantation surgery, s/he has to take dialysis sessions every year and the pain increases in time. Besides, quality of life decreases and s/he would not be cured. However, transplantation would heal him/her and follow-up treatment would be enough. S/He would be healthy enough to work and live without any companion again. Therefore, even if the cost of transplantation exceeds the cost of dialysis; it will become cost-effective in the following years.

In Turkey, dialysis is more expensive than transplantation on yearly basis. Payments for kidney diseases comprise a considerable amount among total health expenditures (5% as direct cost and 15% as indirect cost)26. Although the government pays all the medical costs

26 www.tsn.org.tr/pdf/Turkiye_Bobrek_Hastaliklari_Onleme_ve_Kontrol_Programi.pdf 98

of dialysis patients and transplantation, there are some other costs which are not considered and calculated under this item.

10.4. Cost-Benefit Analysis of Kidney Transplantation in the World

There are many problems in the cost calculation of transplantation. There are comorbidities associated with kidney diseases such as hypertension, diabetes, obesity, metabolic syndromes, dyslipidemia, and hyperuricemia. The main additional diseases are cardiac diseases and diabetes in general. Thus, additional costs related to these likely comorbidities need to be taken into account while calculating the cost of transplantation. However, they differ for every patient and every operation. After-transplantation medical care is another ongoing cost. Many researchers do not consider these items in cost calculations.

Escuredo et al., made a detailed examination for Spain which takes after-Tx follow-up costs into account (Escuredo et al.: 2015). Villa et al., ended up with another result for follow-up costs in Spain as €6,283 (Villa et al.: 2011). ElSharif et al. calculated these costs as medication and examination costs (ElSharif et al.:2010). Freeland assumed these costs in the form of medical care costs for successive years and calculated failed Tx expenditures for the U.S. (Freeland et al.: 1999). Cavallo et al. made a detailed analysis for Tx costs in Italy. They divided the cost into deceased donor and living donor costs with first year and follow-up expenditures of following years including immunosuppression and complications (Cavallo et al.: 2014). Perovic and Jankovic made a 10-year approach for HD and Tx in Serbia (Perovic and Jankovic: 2009). Haller et al., made 12-24 and more than 25 months projection for the costs of HD, deceased donor and living donor (Haller et al.: 2008). Another detailed analysis made by Kontodimopoulos et al., for Greece with different discount rates of the costs of QALY calculated the costs of HD and PD, living donor and deceased donor transplant with minimum and maximum values (Kontodimopoulos et al.: 2008).

Sainsaulieu et al. analyzed the cost of renal Tx between 2010 and 2012 for France. They conclude that deceased donor costs vary between €13,835 and €20,050 while it is €13,601 for living donors (Sainsaulieu et al.: 2014). Guerra Junior et al. made an analysis of after- Tx costs for a 5-year perspective in Brazil and concluded with an amount of R$78,360 (Guerra Junior et al.: 2015). A. Nassir and his colleagues attempted to calculate relative

costs (estimated and realized payments) for the U.S. by analyzing 19,603 transplants at 166 different centers between 2007 and 2009. They conclude that the mean observed cost per patient per center is $65,266 (range is between $55,094 and $71,624). Roselli, Rueda and Diaz made a detailed cost-effectiveness analysis of kidney Tx and ESRD dialysis for Colombia. Their discounted average total cost for five years is $76,718 for Tx and $76,891 for dialysis. They used a QALY value per patient that is 2.98 for Tx and 2.10 for HD (Roselli et al.: 2015). Younis et al. calculated the follow-up expenditures after-Tx to be $2,960 (Younis et al.: 2015). Rocha et al., found that follow-up costs in Spain for Tx patients is €6,526.32 on a yearly basis (Rocha et al.: 2012).

10.5. Cost Analysis of Hemodialysis

Survival of a HD patient about 13,8 years in average and 21,6 years in case s/he undergoes transplant surgery (Hariharan et al.: 2000). Therefore this cost-analysis is based on 14 years for HD and 22 years for transplantation. According to Becker and Elias (Becker and Elias: 2014) and Wong et al. (2012) average transplantation waiting time is 4-5 years. This period varies depending on the country and patient. A survey by Kubal revealed that average waiting time for a kidney for an adult patient is 1088 days in England (Kubal: 2012). However the Organ, Tissue Transplantation and Dialysis Services Department is not capable of providing solid data regarding average waiting time on the basis of their declaration stating this period varies with respect to the patient, availability of deceased donors and the region. Recent studies in Turkey do not reveal any proper waiting time data therefore absolute waiting time for a wait-listed dialysis patient is assumed to be 5 years.

The calculation is based on the following scenario: two patients are treated as kidney patients at time T. At this point, they are both enrolled in the waiting list. 5 years later, one of these patients receives a kidney at time T0 and the other one continues on dialysis. Thus, in this 5-year period, their costs are the same. The difference between these patients begins from this point on, T0. The dialysis patient continues dialysis sessions; s/he cannot work and cannot attend the business life. On the other hand, the transplant-patient recovers health and attends into labor force. According to Hariharan, average remaining life of the dialysis patient is 10 years and 17 years for the transplant patient. In this period, the dialysis patient suffers life-quality loss however the transplant patient gains a better life quality.

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The calculation comprises the future value of the costs. In financial and economic analyses, rate of inflation is utilized for future value calculations. For the year 2016, the rate of inflation was officially stated to be 8.53% in Turkey therefore this ratio is used to calculate the future costs of each component.

There are primary and secondary costs to be taken into consideration. Primary costs are; dialysis costs, costs of labor force loss , companion costs, QALY, diagnosis and test costs where patient’s suffering from the disease and its comorbidities, the discomfort of the next of kin, despondency of the patient on beloved ones etc. are some examples of the secondary costs. There are numerous items those could be regarded as secondary costs which depend on circumstances. Nevertheless such items cannot be calculated or there is no exact references to monetarize them, therefore only the primary costs are include in the calculations.

The cost of dialysis could be found easily by multiplying the cost of each session with the number of sessions in a week and weeks in a year; that is TRY 172.8 x 3 x 52 = TRY 26,956.80. With a 10 years perspective based on an 8.53% future value ratio, total dialysis cost is calculated to be TRY 290,878. For the calculation of the loss of labor, minimum wage is assumed to be the basis. According to Regulation of Disability Identification Procedures published in the Official Gazette No: 28727 on August 3rd, 2013; every dialysis patient is regarded disabled and all disabled people are paid a disability wage which amounts to the minimum wage that is TRY 1,300 for 2016. One-year labor force loss is (12 x TRY 1,300 = ) TRY 15,600 and the total cost of labor force loss on a future value rate of 8.53% for 10 years is calculated to be TRY 168,332.

The government makes a payment for the companion who is responsible for taking care of the patient. Such a payment is possible only if the patient has a 60% disability report which is given from a general hospital upon full check-up. This ratio means that there is a progression in the disease, i.e. the patient cannot personally look after him/herself and needs a caretaker. The government pays two thirds of minimum wage to the caretaker, so the amount given to the companion is TRY 1300 x 2/3 = TRY 867 per month and total annual payment is (12 x TRY 867) ≈ TRY 10,400. The total costs for 10 years with the same discount rate are TRY 112,221.

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Another component that has to be considered is the QALY-loss of the patient. This item is used as per the estimation of Becker and Elias and the details are given in section 12.3 of this thesis. The value is derived from reports published by WHO. QALY-loss for the first year is calculated to be TRY 6,306. The total amount with future value rate of 8.53% for 10 years is TRY 68,045.

The last component for the calculations is the diagnosis and test costs. Every patient must have monthly biochemistry and blood count tests, crp-hormone and serology tests quarterly, usg-chest radiography and check-up every six months, and psychologist and psychiatrist diagnoses every month. The total costs of these tests for a year are TRY 245. This cost is derived from the data taken from Atatürk Education and Research Hospital. The total costs for 10 years based on the same discount rate are calculated to be TRY 2,644.

A dialysis patient is not able to work. There are some exceptions such as IT workers or jobs those are suitable to work from home however these are quite exceptional. The sum of all items mentioned in the preceding paragraphs is TRY 642,120 is a base value since there are some other costs those could be added such as comorbidities which most patients catch (i.e. cardiac disease or diabetes) and social costs or secondary costs.

Table 12: Cost of a Hemodialysis Patient

Years Dialysis Labor loss Companion QALY Diagnosis and Total Costs Costs Costs Test Costs 0 26,957 15,600 10,400 6,306 245.0 59,508 1 29,256 16,931 11,287 6,844 265.9 64,584 2 29,305 16,959 11,306 6,855 266.3 64,692 3 29,322 16,969 11,313 6,859 266.5 64,729 4 29,331 16,974 11,316 6,861 266.6 64,748 5 29,336 16,977 11,318 6,862 266.6 64,760 6 29,339 16,979 11,319 6,863 266.7 64,768 7 29,342 16,980 11,320 6,864 266.7 64,773 8 29,344 16,981 11,321 6,864 266.7 64,777 9 29,345 16,982 11,321 6,865 266.7 64,780 Total* 290,877 168,332 112,221 68,045 2,643.7 642,120

* All costs in TRY

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The costs of PD or home-dialysis are open to debate. Social Security payment for these types of dialysis is the same and the vast majority of the patients are HD patients (92% of the dialysis patients are HD patients) (TNA Registry Report: 2014). Therefore this calculation also applies for other types of dialysis.

The cost of dialysis is not the only expenditure for a dialysis patient and there are extra costs involved such as cost of labor force loss, companion, QALY and, diagnosis and other tests which add up to more than TRY 642,000 that is the loss for one single patient. This figure becomes much more meaningful when it is multiplied with the total number of dialysis patients. Policymakers have to take preventive health measures in order to reduce the number of patients. It should be noted that HD or Tx are temporary solutions.

10.6. Cost Analysis of Transplantation

The costs of transplantation are different than those of dialysis because of many variables. For example, grafting could be from a living or a deceased donor and follow-up costs of a living donor also amount to some value. The condition of the grafted organ is another factor effective on the cost whereas the medical history of the donor is very important. The donor being a smoker or heavy drinker (maybe an alcoholic) is another case that would cause some further troubles. Main difference is attributed to comorbidities because every comorbidity would result with different costs. Medical care costs would also lead to a difference. Surgery of a dialysis patient with diabetics differs from a patient who has cardiac diseases. The period of hospital stay of the donor or the recipient is another factor to consider. In general, hospital stay of a donor is 5 to 7 days. Afterwards, residential care is enough to follow-up recovery. On the other hand, follow-up for the recipient depends on his/her medical conditions. Especially, the first 6 months are of great importance for making a decision that the body accepts the kidney or not. The quality of the surgery team, hospital and other latent variables would also affect the total cost. It is not possible to easily decompose every potential variable thus the costs of standard procedures without any other comorbidity are considered in the calculation of the cost of Tx.

Another factor that affects the cost is after-Tx care costs. The patient must use some immunosuppressive drugs in order to avert graft rejection. It is a normal reflex for a body to reject a foreign organ so the immune system must be depressed. For that reason,

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invention of immunosuppressives mark an era for organ transplantations. There are some standard drugs for depressing the immune system such as prednisolone, azathioprine, cyclosporine, tacrolimus, cellcept, rapamune and belatacept. The period and dosage of these drugs are generally different for each patient. Guerra Junior et al. (2015) made a graft survival analysis of cyclosporine + azathioprine and tacrolimus + siromilus (Guerra et al.: 2015). The costs of immunosuppressive are negligible. The patient takes these drugs after the operation intensely. After 3 months, the dosage is reduced, only 6 months later it is can be recognized that the body accepted the transplanted organ or not. Dosage of the drugs is further reduced. At the end of the second year, there is almost no drug left in use.

According to the data taken from the Atatürk Education and Research Hospital, the cost of a donor before, during and after Tx is TRY 1,850. Service costs vary between TRY 1,979 and TRY 2,770. The price and materials breakdown are given in Appendix 327. The cost of Tx from a living donor to a recipient ranges between TRY 36,358 (USD 12,444) and TRY 38,320 (USD 13,115). Service costs are between TRY 5,104 and TRY 8,532. The detailed breakdown of the materials that are used for a patient is also given in Appendix 3. The cost of a recipient who is transplanted from a deceased donor costs between TRY 42,156 and TRY 52,742. This difference is attributed to service costs which are between TRY 8,985 and TRY 30,751. The following items are included throughout the cost calculation:

 Labor costs of polyclinic,  Labor costs of pre-operative preparation crew,  Labor costs of surgical team,  Medical material costs,  Drug and serum expenditures,  Analysis and examination expenditures before and after the operation,  Direct material and labor costs  Hospitalization.

Since there are so many variables for cost analysis, the total cost may significantly vary depending on the consideration of each component. Total cost of Tx (either from a living or a deceased donor) is between TRY 36,400 (USD 12,444) and TRY 53,000 (USD

27 Summarized list of materials are given in Appendix 3. Detailed list of all materials, examinations and evaluations are available upon request from the author. 104

18,120) and the average cost is TRY 44,700 (USD 15,300) which will be used for calculating the cost of a transplanted recipient.

For calculating the total costs of transplantation, Tx costs with follow-up medication have to be considered, nevertheless the cost is not fixed. In some cases, the body rejects the transplanted kidney however re-transplantation costs are not calculated. The calculation is based on full recovery of the patient after the operation.

Another component of the after-Tx cost is the salary of the recovered patient. The cost of labor force loss is calculated for a HD patient but this payment is in terms of a social aid. The patient is not able work in this period. On the other hand, a transplanted patient, upon recovering full health, returns back into business life and can make money, therefore the salary of the recovered patient must be included in the analysis. Minimum wage civil servant salary is TRY 2,151 in 2016. Annual income is 12 x TRY 2,151 = TRY 25,812. With a discount rate of 8.53% for 17 years, the total is calculated to be TRY 553,397. Assuming that this patient is not available for work in the first year of surgery, salary of the first year would not be considered. In this case the total would be TRY 527,585 which is the NPV of the total income for 16 years.

There is a difference of 8 years between the expected lifetime of a dialysis patient and a transplanted patient. Value of this difference in lifetime must be included in the analysis. For calculating the value, the Value of a Statistical Life (VSL) is employed. Unfortunately, there is no VSL value calculated for Turkey. VSL consists of many variables and the amount differs from sector to sector. Viscusi and Aldy tried to analyze and generate a VSL value (Viscusi and Aldy: 2003) and included 26 dependent and 41 independent variables. Their calculations are based on the fatal injury risk of the occupation, hourly/monthly/yearly wages, age and willingness to pay. Only the hedonic wage pricing consists of 5 different variables with constant and error terms.

Calculations of Viscusi and Aldy change with respect to the sectors. Viscusi and Aldy consulted the Aviation industry, an environmental protection agency, food and nutrition service providers, a product safety commission, a food safety inspection agency and the food and drug administration for VSL in the U.S. and ended up with different results in

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different times. OECD prepared a meta-analysis of VSL estimates which is a comprehensive study28 including the analysis of 95 different articles.

Calculation of VSL requires some sort of data that is not available. These data are restricted by law and must be calculated by the government, the Social Security Institution or the Ministry of Health. Since there is no consistent data available, the Eurozone VSL data is used. The Eurozone VSL calculated by WHO is €3,730,925 maximum, €1,243,642 minimum and €2,487,283 as base price. These values are taken from the Health Economic Assessment Tool of the WHO website. The VSL can be calculated by converting this value to year 2016 using the purchasing power parity (PPP). The calculation is as follows: 2,487,283 x 1.2916 x 1.309846 = TRY 4,207,978.

The average expected lifetime for a 15 years old person was 64.3 years in 201429. This results in a total lifetime of 79.3 years. Accordingly, a monetary equivalent of an 8-years lifetime would be calculated as follows: TRY (4,207,978 / 79.3) x 8 = TRY 424,512.

In the academic literature, the evaluation of the costs of Tx does not depend on exact data. Actually there are so many variables for this evaluation and the analysis in this thesis is based on exact and real data taken from the Atatürk Education and Research Hospital in Ankara. This evaluation includes many variables and calculations for a transplanted patient with a living donor and deceased donor, cost of surgery, follow-up costs before and after the surgery, medications and other determinants. The total amount indicates that the cost of a transplant patient is more than the payment made by the state insurance system.

28 http://www.oecd.org/env/tools-evaluation/env-value-statistical-life.htm 29 http://www.tuik.gov.tr/PreHaberBultenleri.do?id=18618 106

11. COST-BENEFIT ANALYSIS OF KIDNEY TRANSPLANTATION IN TURKEY

The calculations hereto shall be used throughout the cost-benefit analysis of kidney transplantation. The outcome of this analysis would be the benefit over the difference of transplantation surgery and dialysis of a patient under minimum standards. The items to be included in the analysis would be the primary and secondary costs. The monetary equivalent of secondary and social benefits cannot be calculated straightly and thus are not included in the calculations.

The costs of HD patients are neutralized since there are benefits in case they have transplant surgeries. Even though there is a benefit, the cost of dialysis is not included in the cost-benefit analysis owing to the fact that it shall not be required after the surgery. On the contrary, the transplant patient will join his/her social and economic environment, become productive and generate income. Besides, his/her quality of life would increase; s/he would be able to satisfy his/her personal needs without help and may lead a longer life. Cost of Tx, follow-up costs and the cost of the first year after the surgery of the donor shall be considered on the cost side. Although probable comorbidities or the case of kidney transplant rejection give rise to additional costs, they are not included in the calculations.

Cost

Average cost of transplantation are calculated on the basis of hospital data in the previous sections and is found to be TRY 44,700, according to costs of 2016, which includes costs of medication, examination, hospital admission before, during and after surgery as well as the costs of the surgery team and nurses. Similar costs are included in the costs of the donor that is calculated to be TRY 1,850. In addition to these, follow-up cost for the first year after surgery are calculated updating the follow-up cost of Yiğit and Erdem (Yiğit

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& Erdem: 2015) compatible to 2016 prices (rate of inflation 8.53%). As a result, total cost of a transplant patient is calculated to be TRY 55,941.96.

Benefit

There is an 8-years long difference on average between the lifetime of a dialysis patient and a transplant patient (Hariharan: 2003). The monetary equivalent of this time period was calculated to be TRY 424,512 in the previous section using VSL. The fact that the patient joins the economic market should be included on the benefit side. At this stage, different amounts of salaries could be considered in terms of the income of the patient. Salary earnings are calculated on the basis of minimum civil servant salary of 2016 since calculations are based on minimum amounts. The calculations assume that a transplant patient survives for 21 years and works for 15 years. There are two main reasons for this assumption which are (i) the patient waits for 5 to 6 years before transplantation and survives for 21 years, (ii) depending on his/her age, the patient could retire. A sensitivity analysis using different survival times and salaries is possible. As a result, salary earnings for 15 years with an inflation rate of 8.53% is calculated to be TRY 730,443.4

Table 13: The cost-benefit analysis of transplantation

Cost Benefit Explanation Transplanted Patient -44,700 Transplantation costs Follow-up Costs for -9,392 Second Year Donor -1,850 Surgery costs of donor Value of Statistical Life Monetary equivalent of + 424,512 (VSL) extra 8 years of lifetime The earnings of Salary Earnings +730,443 transplanted patient in 15 years -55,941,96 +1,154,956 1,099,014 TOTAL ( USD 18,558) (USD 383,134) (USD 364,576)

* All costs in TRY

Adding up the items on the benefit and cost sides, total benefit is found to be TRY 1,099,014. It is noteworthy that this huge amount is the benefit gained in case only one

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patient is transplanted with costs based on minimum values. This amount would inevitably increase when different items are included. The following section comprises a sensitivity analysis on the basis of this benefit per patient value. This analysis is remarkable in terms of observing the benefit over a change in the number of donors or a decrease in the number of wait-listed patients. The total benefit as a result of the calculations would project the economic gain(s) through increasing the number of transplantation surgeries.

11.1. Sensitivity Analysis

According to 2015 data of the Ministry of Health, number of wait-listed patients is 22,601, number of transplants is 3,204 and number of donors is 3,919 (3,447 living donors and 472 deceased donors) in Turkey. The sensitivity analysis is based on these data with 5%, 7% and 10% changes on numbers of transplants, donors and wait-listed patients. Although the number of patients with kidney disease (60,101 persons) is almost three times greater than the number of people on the waiting list, this figure is not taken into account for the sensitivity analysis. In a case the system is converted into an opt-out regime, donation rates would increase by 5% to 7%, therefore these percentages are used in the sensitivity analysis. The Ministry of Health started a program for increasing the donations and ran an extensive advertising and promotion activity which increased the amount of donations by 10%.

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Table 14: Sensitivity analysis of change in donation, transplantation and waiting list figures

Change in # Change in Amount of Wait- Change in the Transplantation of Total gain (TRY) Listed # of Donors Quantity Change Patients 1,099,014 2015 22,601 3,204 3,919 (per person) 5% increase in # of 22,405 3,400 4,115 196 215,406,693 donors 7% increase in # of 22,327 3,478 4,193 274 301,129,765 donors 10% increase in # 22,209 3,596 4,311 392 430,813,386 of donors 5% change in 22,441 3364 4,079 160 175,842,198 transplantation Q 7% change in 22,377 3,428 4,143 224 246,179,078 transplantation Q 10% change in 22,281 3,524 4,239 320 351,684,397 transplantation Q

5% decrease in the # of wait–listed 214,71 4,334 5,049 1,130 1,241,885,526 patients

7% decrease in the # of wait–listed 21,019 4,786 5,501 1,582 1,738,639,727 patients

10% decrease in the # of wait–listed 20,341 5,464 6,179 2,260 2,483,771,052 patients

Sensitivity analysis is based on the gains upon:

i. Changes in the number of donors, ii. Changes in the number of transplantations, iii. Changes in number of wait-listed patients.

The reason for considering the changes in the number of transplantations and change in the number of donors is obvious. However the reason for considering the change in the number of wait-listed patients is attributed to the facts that there may be patients who are enrolled on the waiting list but may not be willing to be transplanted; the patient could have found a kidney from the black market but may still be on the list or the patient may find a matching donor because of a monetary incentive after enrolling into waiting list. In the first part, increase in the number of donors is not remarkable however the total gain is

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astonishing. In the second part, percentage changes in transplantation numbers result with less difference compared to that of a change in donors. Same percentage changes have enormous effects when applied to the figures of the waiting list. Amount of change in patients is almost nine times greater than the change in the number of transplantations. This change in quantity has an outstanding effect on total gain. This sensitivity analysis proves that any policy that leads to an increase in the number of transplantations would also yield a significant economic gain.

11.2. Uncalculated Elements

The elements of “costs” and “benefits” are calculated in the previous section. There are some secondary costs and benefits those could be calculated with different methods. They could be evaluated by “cost-effectiveness” and/or “cost-utility” methods but they have to have enough number of variables, data and reference points which are not available within the scope of this thesis. Social benefit of a transplant patient, transaction costs and social benefit of the patient’s next of kin could be specified as secondary costs and benefits.

Social benefit of a transplant patient could be specified with the relief from the disease and end of suffering. However this moral gain has no real monetary equivalent. Transaction costs could also be specified as part of secondary costs. One of them is tracking the organ trafficking. General characteristic of organ trafficking was given in Chapter 7, “Kidney in Black Market and Transplant Tourism”.

Since organ trafficking is an organized crime, this organization consist of middlemen, hospitals, surgeons and even officers. It is an international organization, so tracking and catching these traffickers is of utmost importance, a delicate and professional mission. The question is whether it is worth to track and catch these smugglers or not? There are some human traffickers which try and find countless ways for organ trafficking all over the world. On the other side, there is a small group of well-educated, organized agents to catch these criminals. Although these criminals are captured, deficiencies in laws and regulations (either in Turkey or in another country) may end up with adjudications leading to the release of these criminals. These criminals are settled especially in countries which do not have harsh sanctions and have legal deficiencies. The regulations are consolidated but exceptions in the law give opportunity for criminals to get out. If a trafficker is found

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guilty, s/he is sentenced to a penalty of imprisonment from 2 to 5 years in Turkey. However, according to TPC Article 92, a middleman can slip through the net. Another transaction cost is re-directing the doctors to the remaining patients. Although the doctors will have the same shifts, the amount and diversity of patients will differ.

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12. AMOUNT OF MONETARY INCENTIVE AND ITS EFFECTS ON KIDNEY DONATION IN TURKEY

CKD is a worldwide health problem and is growing rapidly (Said et al.: 2015). Although PD and HD are treatments to overcome the disease, they are not sufficient to cure CKD but only delay an inevitable death. CKD patients become ESRD patients at the last stage of their illness and the only way to cure these ESRD patients is organ transplantation. ESRD patients are increasing all around the world at a rate of almost 7% to 8% per year (Bethoux et al.: 1999). ESRD patients have longer survival after renal replacement therapy (RTT) (Perez-Saez et al.: 2016) and successful transplants save lives (Wolfe et al.: 1999).

Organ transplantation has been the milestone for most of organ de-functioning diseases in Medicine (Kittur et al.: 1991). Kidney transplantation is considered as a cost effective alternative compared to dialysis techniques (Salamzadeh et al.: 2014). In 2010 the annual cost of ESRD was $32.9 billion in the U.S. and the cost of kidney transplantation was $2.8 billion (Nassir et al.: 2015). A number of studies show that kidney transplantation is more cost effective than dialysis over a certain period of time (Synder et al.: 2013).

There is a disparity between the number of transplantable kidneys and availability of kidneys to be transplanted (Choi et al.: 2014). This shortage becomes an unsolved problem which results with an increase in the number of people on waiting list and the waiting time. The success of kidney transplantation contributes to an increase in demand (Gill et al.: 2005). However longer waiting times may limit the success of transplantation and survival (Gill et al.: 2005). The median waiting time between enrollment in list and transplantation surgery was 3 years in 1999 (Gaston et al: 2002) while in 2013, 72% of ESRD patients are transplanted within 5 years from deceased donors in the U.S. (Hart et al.: 2014, p. 13). In Turkey the ratio of patients having RTT (either HD or PD) up to 10 years is more than 90% (Seyahi et al.: 2015). Increase in time from 3 years to 5 years within a decade shows that actual donation techniques have not been effective to meet the demand.

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Increase in the number of wait-listed patients forces patients to seek for an illegal solution. Updating rules and regulations have not yielded the expected impact for the last two decades and organ trafficking has become a worldwide crime. Organs of executed criminals were being taken till 2008 in China and there was a completely free market until 1994 in India. A legal regulation was enacted however did not change the situation. Many surveys are reported about organ trafficking in Africa and the organ business is filmed in Moldavia. Although organ trading is forbidden, buying and selling organs is very common in Afghanistan, Iraq and Bangladesh (Novelli et al.: 2007).

Besides other proposals that are discussed in the previous sections; monetary incentive is an effective way to solve the kidney shortage problem. Iranian Model shows the effectiveness of payment for the kidney donation. In the Iranian Model, the government or an authorized entity makes a lump sum payment; if the donor demands an additional payment, it will be paid by the recipient. If the recipient cannot afford this amount, the remaining would be paid by a charitable foundation (Ghods and Savaj: 2006).

There is an ongoing debate about the ethical perspective and payment method of a monetary incentive. Argument regarding ethical concerns is given in the next paragraphs. There are two ways for monetary incentives which are indirect and direct incentives. Indirect incentives could include tax deduction, insurance and health coverage and reimbursement of funeral expenses (Peters: 1991). In Pennsylvania, payment for funeral expenses was proposed but was not put into effect (Ubel et al.: 2000). Other proposals about incentives for donor registration could be (Van Dijk: 2007, p.9):

. making a discount on health insurance premiums, . assigning a higher order on the waiting list for future organ needs

In order to reduce the number of the refusals by next of kin to donate the organs of a deceased, following incentives could be considered:

. rewarding surviving relatives by paying funeral expenses, . offering more professional support and provide counselling to surviving relatives.

The American Society of Transplantation and the American Society of Transplant Surgeons organized a working group on Incentives for Living Donors in 2011 and reported

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their result as a guideline for the development of a regulated system of incentives for deceased and living donation (Minnesota: 2011) which is as follows:

1) Each country implementing a system of incentives could have a legal and regulatory framework for the process, 2) The entire process must be transparent and subject to governmental and international oversight, 3) The incentive could be provided by the state or a state-recognized third party. Under well-defined, transparent and regulated circumstances, prospective recipients may help fund a charity that supports the program. There is no direct payment from the recipient to the donor and supporting the charity will not lead to a priority on the waiting list, 4) Allocation of the organ(s) could be performed according to a recognized single system of that particular country (similar to UNOS in the U.S.) using a predefined and transparent algorithm so that everyone on the list would have an opportunity to be transplanted. Kidneys would be allocated to the number 1 person on the list (as determined by defined and transparent criteria), 5) There could be a plan for administration and rigorous oversight to ensure that criteria for evaluation, acceptance, allocation and provision of the incentive to the donor (or donor family) are being monitored, 6) The donation could be anonymous and non-directed, 7) No other solid organ donor incentive plan would be legal, 8) There could be legislation to govern wrongdoing and how centers would be censured, including criminal sanctions and fines, if wrongdoing is identified.

There are some other suggestions about the way of making the payment. Matas and Schnitzler analyzed the attitude of citizens about monetary incentive concept. They ended up with an interval between $41,830 and $67,506 which is more or less equal to the cost of dialysis. Upon this assessment, they proposed that the payment could be equal to the gain from the dialysis costs (Matas and Schnitzler: 2003, p. 219).

Becker and Elias tried to examine the effect of monetary incentive on kidney donation. They calculated the sum of monetary loss of a living donor which could at least be equal to the monetary incentive. Their proposal is based on losses such as economic loss, QALY

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loss, and risk of death (Becker and Elias: 2007). The quantity of this proposal is closer to the price of a kidney in the black-market and explains the logical limit of the monetary incentive that the possible unrelated donors would accept.

Direct payment to the organ donors is criticized based on its ethical aspects. Thus, some academicians suggest passive or secondary incentives which propose a small discount while the donor applies for a driving license just like the Georgian government makes a $7 discount from the fee of driving licenses of donors. In England, citizens are obliged to mark one of the boxes one of which approves becoming a donor while the other reads “not now”. Although this passive strategy is simple, it results with a comparable growth in donation rates according the researchers (Jasper et al.: 1999, p.2183; DeJong et al.: 1995).

12.1. Kidney Transplantation and Dialysis in Turkey

Since 1975, the year the first kidney transplantation surgery was performed (Karaali and Haberal: 2005), transplantation surgery improved significantly both in terms of quality and quantity in Turkey. The legal legislations enacted and updated through time, regulated the system and led to an increase in quality, speed and safety in transplantation. However the gap between the demand and supply for kidneys is growing in Turkey as it is the same case all around the world.

According to IRODaT registry reports, Turkey is the leading country with 46.6 pmp in living kidney donor ratio and 3rd country in living donor ratio. However deceased kidney donor ratio is very low (5 pmp) (IRODaT: 2014). The living donor ratio may be explained by kinship. In fact, the countries that are ranked in the upper rows in the list have close and common national cultural heritages. On the other hand the reasons of low deceased donation levels are different which can either be of national, cultural or religious origin.

According to 2014 data of the Ministry of Health that are published for public information on the website www.organ.saglik.gov.tr, there were more than 59,000 CKD patients, 25,337 of these patients were on the waiting list and 4,263 were transplanted (www.organ.saglik.gov.tr). All of the costs of dialysis and transplantation patients are covered by Social Insurance System (SIS) including the costs of grafting organ from living or deceased donors. In fact, the cost of only 59% of CKD patients were covered by SIS and the rest were paying their expenses on their own.

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TNA publishes registry reports annually since 1990 (www.tsn.org.tr). These reports are considered official reports of Turkey by other international associations such as ERA- ETDA. According to the TNA registry report for 2014 (TNA: 2105) CKD prevalence in 2013 was 870 (children included) and incidence was 138 (Tatar: 2015, p.5). Private HD centers are crucial for dialysis patients. Almost 68% of HD patients attend privately held dialysis centers. As of 2015, there were 839 HD centers and 340 of them were privately held (Tatar: 2015, pp.5-10).

The number of HD patients is increasing every year (Figure 8). However the change in numbers between 2012 and 2014 is not significant (Tatar: 2015, p.7). These results are matching with the official site of Ministry of Health that lists the number of patients for five years (www.organ.saglik.gov.tr). In this section, official numbers of the Ministry of Health are considered as the reliable data set. Accordingly, the number of transplantations in 2014 is 4,263 and the number of patients on the waiting list is 25,337. Only one (1) donor death case after the transplantation surgery is reported. All of the dialysis and transplantation expenses either for donors or for recipients are paid by the SIS where 59% of dialysis patients are SIS registered. The data on the official website begins as of 2011 and there are no radical changes in the number of dialysis patients, number of donors and number of transplantations in the years listed (2011-2015).

12.2. Economic Analysis of Monetary Incentive

A valid proposal for the kidney shortage is using incentives for living unrelated donors. The demand for transplantable kidneys does not meet the supply. If kidneys were merchandised the gap between supply and demand would mean the price was too low (Leider and Roth: 2010). This could increase the living donor transplants but it is not a sufficient solution to mark it as an increase in demand (Matas: 2004, p.2007). In the U.S. it is estimated that if all potential kidney donors become actual donors, the current demand would double (Sheehy: 2003).

One possible solution is to develop a regulated payment system to living kidney donors (Matas: 2004, 2008). Especially considering the Iranian model, the academicians try to formulate and standardize the structure the amount of monetary incentives. In another article, Matas and Schnitzler highlight that a substantial payment, like $100,000, could be

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made to a vendor that would be cost-neutral to the health care system because of the savings of a transplant over ongoing dialysis costs (Matas and Schnitzler: 2004).

Gordon et al., found that participants are willing to donate a kidney for an enough “compensation” which will cover the debts of the donor (Gordon et al.: 2015). Barnieh et al. made a cost-effectiveness analysis of a paid living donor strategy. According to this analysis, the strategy that increases transplantation rates by 5% through paying living donors $10,000 is compared with the current organ donation system, with incremental cost-savings of $340 and a gain of 0.11 QALYs over a patient’s lifetime. Both the payments and the transplantations are increased from $10,000 to $50,000 and from 1% to 50% respectively. The study concludes that the paid strategy is almost more effective with contrast to the current donation system (Barieh et al.: 2013).

Gaston et al. made an estimate for the cost of their proposal including costs for loss of amenities and anxiety ($5,000 direct payment or a $10,000 tax deduction) and concluded that cost per donor was $23,525 - $32,800 (Gaston et al.: 2006, p.2552) which is almost half of a single year dialysis costs ($58,000) (Field et al.: 2000).

Al Sebayel et al. provided a qualitative review of a 7-year experience with incentive based procurement system (IBPS) which was applied by the Mobile Donor Action Team (MDAT) and found that use of financial incentives resulted in a 3-fold increase in donation rates in Riyadh (Al Sebayel et al.: 2014). Beard, Kasermann and Saba tried to reach educational costs for increasing deceased organ donation. They calculated that the costs for generating one additional deceased organ donor, is $21,300 for professional training expenditures and $55,000 for public education (Beard et al.: 2004). Mayrhofer- Reinhartshuber et al. reached in a questionnaire survey that financial incentive to organ donation seems to be a strict taboo for most people in Australia (Mayrhofer-Reinhartshuber et al.: 2006).

Byrne and Thompson categorized incentive proposals into two groups explicitly: (i) financial incentives that include cash payments, (ii) contributions to burial expenses and discounts on taxes (Byrne and Thompson: 2001). The supporters of these proposal are Brams (1977), Schwindt and Vining (1986), Rinehart (1988), Cohen (1989), Barney and Reynolds (1989), Blair and Kaserman (1991), Kaserman and Barnett (1991), Kittur et al.

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(1991), Peters (1991), Altshuler and Evanisko (1992), Barnett et al. (1992) and Khanna (1992).

One of the solid and logical proposals for monetary incentives to living kidney donor was made by Becker and Elias. They began with analyzing the gap between kidney supply and demand. Then they determined the components of a monetary incentive which is based on the donor’s losses. 3 main components were included in the equation of their calculation: (i) monetary incentive for death risk, (ii) monetary incentive for healing period, (iii) the equivalent of life-quality loss. Apart from the matters of concern mentioned, their article differs in terms of the fact that they focused on the effect of monetary incentive which could decrease the demand and effect of the decrease-in-demand on the price of an organ.

This section replicates the calculations of Becker and Elias for the price of a kidney. The first component is the monetary equivalent for death risk. In the U.S., loss of life during/after the transplant surgery is about 1%. In Turkey, only one (1) case of death after transplant surgery was reported among the total 4,263 surgeries in 2014. Calculating this ratio for Turkey is yields 0.0235% (See Appendix 1). This is the only solid data given from the Ministry of Health Organ, Tissue, Transplantation and Dialysis Services official website. Becker and Elias used VSL for the death-risk component. There is no calculated VSL for Turkey therefore VSL for Eurozone calculated by WHO which is 2,487,283 Euro30 is used. If this quantity is converted to TRY and multiplied by the formerly calculated ratio (0.0235%); the statistical value of human life for the probability of loss of life during/after a transplant surgery is approximately TRY 989. Details of the conversion and calculation are given in the Appendix 1. Different VSL values are considered in the sensitivity analysis of this thesis

The healing period after the surgery for donor is almost 4 weeks (Becker and Elias: 2007, p. 10). The second component of the monetary incentive is the value of monetary loss during the treatment process. Although this period is not enough to full-recovery it is sufficient to return casual daily business-life. The rest of the period is foreseen as medical treatment. For the loss of donor during the recovery period, minimum civil servant salary is used which is TRY 2,151 in 2016. There are 52 weeks in a year and annual gain of a civil servant is divided by 52. The result is multiplied by 4 and total monetary equivalent of

30http://www.heatwalkingcycling.org/index.php?pg=requirementsandact=vslandPHPSESSID=q3jkco40bnm8 aj7poon2v765o5 119

monetary-loss during the recovery period is approximately TRY 1,985.5 (See Appendix 1). This value has primarily direct relationship with VSL. In general VSL is calculated for the health sector (Viscusi and Aldy: 2003)31.

The amount of the value of change in life-quality is the third component. This component also needs the VSL and it is multiplied by QALY however there is no calculated QALY for Turkey therefore the exact QALY value of Becker and Elias is used. Actually it does not differ so much because the average value is more or less the same. Since the quantity is so small, difference in QALY will not lead to drastic changes. The QALY they used is not explicit however it can be derived from the formula which yields the figure 0.0014985. In light of this information, the quantity of the change in life quality is approximately TRY 5,779.8 (See Appendix 1). Summing up these results yields the optimum monetary incentive for a living donor which is approximately TRY 9,280 (See Appendix 1). The effect of monetary incentive on organ donation could be calculated through the Becker and Elias method. Therefore TRY 35,000 should be used for the cost of transplantation according to Health Notification Application 2016 values.

The only variable in the market is demand. Increase in organ supply wouldn’t enlarge the market and all potential donors can find a potential recipient. Actual demand-in-quantity at the market price is related to the actual number of transplants plus the gap of those waiting for a transplant. Therefore, the change in actual demand should be subtracted from the total value because of the change in price. Therefore, the demand function has unit elasticity. The organ supply wouldn’t have a large negative effect on the transplantation demand 9280 (Becker and Elias: 2007, p. 12). Change in demand is = 25.51%. Since kidney 35000 transplantation has unit elasticity, transplantation demand will be effected by 25.51%32. According to the Ministry of Health official data of 2014, 29,600 patients were on the waiting list. Increase in the number of transplant surgeries would be (29,600 x 25.51%) 7,551. The demand function has unit elasticity so total demand will decrease to (29,600 – 7,551) 22,049. This will be the total demand and if the total transplant amount is subtracted from this amount, the result will be the final gap that is calculated as follows: 22,049 – (7,551 + 4,263) = 10,235. This figure reflects the final total number of patients on the

31Viscusi and Aldy tried to summarize all possible VSL studies up to 2003. For more information see the cited paper, page 109-116. 32 Actual number for 2016 is not calculated since the waiting list data of 2016 is not updated on the official website www.organ.saglik.gov.tr 120

waiting list after a monetary incentive is employed. The difference between supply and demand will not be fully eliminated with this much of an incentive figure yet it will shorten the waiting list.

The number of transplanted patients after the monetary incentive would be (29,600 – 10,235) 19,365 which is the total number of transplanted patients those will help close the 18873 shortage. Then the ratio of closed-gap is = 451%. The ratio of total increase in 4263 7551+4263 transplantation is = 277% and the ratio of decrease in waiting-list will be 1 − 4263 10235 = 65.4%. 29600

How would the donation rates be affected in case a change is made in the amount of the incentive? A sensitivity analysis examining this case is given in the following section.

12.3. Sensitivity Analysis

The effect on waiting list of a monetary incentive for kidney donation is calculated to be 63%. The amount of the incentive is kept at a minimum and is based on the losses of the donor. This figure could be diversified by using different amounts. This section examines the effect of a monetary incentive by altering the VSL value. Calculation of VSL differs according to the variables taken, therefore it varies. The Eurozone VSL calculated by WHO is €3,730,925 maximum, €1,243,642 minimum and €2,487,283 as base price. The sensitivity analysis is based on considering €2,000,000 and €3,000,000 together with these 3 values. Euro is converted into TRY by using OECD PPP data. PPP is a theory that equalizes the ratio of aggregate price levels between two countries, so the currency of one country will have the same purchasing power in a foreign country (Taylor and Taylor: 2004). PPP is a relative measure to assign a value on the living standard of an individual within that country by using factors of each country.

As indicated in previous sections, the effect of a monetary incentive on organ transplantation depends on two factors: the first one is the effect of payment to organ for transplantation costs; and the second is the demand elasticity of organ transplantation (Becker and Elias: 2007). The changes in demand and transplantation figures with respect to price changes are analyzed in this section.

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Since VSL given in the first column differs according to calculation techniques and sectors, VSL is used as a variable in the sensitivity analysis. In the second column, risk of death component is held constant. Since it does not vary with respect to a person or a system, this ratio is taken to be 0.0235% (1/4263). However the change in VSL affects the results.

In the third column, since QALY component is also the same, 0.0014985, it is used as a multiplier (derived from Becker and Elias). Since this column also varies depending on VSL; changes in this column result as the changes in VSL. The monetary equivalent of labor-loss is given in the fourth column. The minimum civil servant salary is taken as the basis for the calculation, thus no change is expected in this column and therefore the number is constant.

Table 15: Change in number of transplantations according to VSL

Total Value of Quality of % % Change in Total Death-Risk Value of Kidney Statistical Life Life (QALY) Change Number of Component Time Value (VSL) (TRY) component in Price Transplantations* (TRY) 2,103,990 494.4 3,153 1,985.5 5,633 10.24 523.24 (€1,243,642)

3,383,594 795.1 5,070 1,985.5 7,851 14.27 495.23 (€2,000,000)

4,207,978 988.9 6,306 1,985.5 9,280 16.87 477.19 (€2,487,283)

5,075,391 1,192.7 7,605 1,985.5 10,784 19.61 458.21 (€3,000,000)

6,311,968 1,483.3 9,458 1,985.5 12,927 23.50 431.15 (€3,730,925)

*% Change in total number of transplants = {[(Gap + Actual number of transplants) x (1 – price elasticity of demand for transplants x % Change in price of transplant / 100)] / Actual number of transplants – 1] x100 (Becker and Elias: 2007, p. 15).

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The price of the kidney ranges between TRY 5,600 and TRY 13,000 after all the components are added. Price elasticity of demand is taken as -1 (Becker and Elias: 2007, p. 10) for kidney transplantation which corresponds to a change in transplantation amounts varying between 431% and 523%. Even if the VSL calculation is based on maximum values, the change in total transplantation amount would still be high.

At this stage, the importance of the components comes into the picture. First of all, since the life of human is in question, value of statistical life must be a known component for the calculations. The death risk component shows the monetary incentive given to a donor in return for having risk of death during or after the surgery. In order to calculate this component, the VSL must also be a known component. The donor experiences a loss in his/her “life-quality” because of an organ deficiency. Although this loss would not be that critical to affect the rest of his/her life substantially, a loss is in question to a certain extent. While this life-quality loss ratio is not given explicitly in the article of Becker and Elias, it is derived from the calculations of Becker and Elias. This ratio is independent from which country or values it is, and is constant. As the last matter, the monetary value of the lost time period must be calculated since the donor loses “time” throughout the healing period.

As seen throughout the previous sections, cost of dialysis is already higher than the cost of transplantation. Hoeyer et al. analyzed the papers about financial support models on social behavior (Hoeyer et al.: 2013). They reached that American people are more consistent than European people in terms of this issue. Adams, Barnett and Kaserman’s survey foresees 117% increase in donation rates with a $1000 incentive and that could double donation rates, up to almost 121% (Adams et al.: 1997). Results of the analysis by Sheehy et al. reveal that even if the organs of all eligible deceased donors are recovered, it would not be sufficient to meet the demand (Sheehy et al.: 2003). These surveys and results of this thesis show that a monetary incentive payment would be an effective solution for shortening the waiting list.

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% change in total number of transplantations 540 530 520 510 500 490 % change in total number 480 of transplantations 470 460 450 440 430 0 5 10 15 20 25

Figure 15: Percent change in total number of transplantations

The graph shows the relation between percent change in price and percent change in transplantation. Minor changes in price result in drastic changes in the number of transplantations. The reason of this fact is attributed to the difference between the numbers of required and actual transplantations.

12.4. The Benefits of Decreasing the Number of Patients on the Waiting List

According to the data provided by the Ministry of Health, waiting time on the kidney waiting-list is approximately 7 years however finding a kidney within this period is not certain. The majority of kidney patients are above 60 years old; therefore survival of these patients within this waiting period is painful and diabetics and cardiac failures arise together with the kidney failure (Stel et al.: 2012). When the necessity of providing physiological support to the patients is considered, the costs of renal failure disease further increases. Besides, these expenditures are not enough to heal the disease.

Shortening in waiting time means that the patients would get healthy again sooner than anticipated. A dialysis patient cannot be fully productive during s/he suffers from the disease and besides always needs support and medical care, that is every dialysis patient depends on someone else.

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Diagnosis of kidney disease takes time. The patient must be monitored for at least 3 months. There has to be a period to diagnose the patient as a kidney patient. However this process could take more time than expected. The expenses till the beginning of dialysis are paid by patient himself/herself. Moreover, contracts of insurance companies may not cover the costs. Thus, all these expenses result with a loss of wealth.

Extension of waiting time is also a factor affecting the recovery of a patient during and after transplantation. If the recipient suffers from ESRD for a long time, s/he becomes ineligible for transplantation. Death is a matter of time for this kind of patients. The extension of waiting time causes a major decrease in the quality of life of the patients and leads to considerable deterioration. Patients and beloved ones start having more troubles in time. Therefore, loss of social welfare for this type of patients and their next of kin is almost inevitable.

The difference between supply and demand results in an extension of waiting time. This extension somehow compels patients on the waiting list to look for illegal ways to find a suitable kidney. Since this problem cannot be eliminated in a short time, patients tend to attempt different, illegal and unethical methods. The governments do not have solid and quick solutions for ESRD patients therefore this gap is served by the kidney black market. It is obvious that, donation systems cannot meet the demand. Donation encouraging systems, mechanisms and advertisement policies are not satisfying the needs and patients are dying day by day. They may not have enough time for a legally recognized proper kidney. If a patient has an opportunity of having a living donor from his/her spouse or next of kin, s/he receives it. Otherwise, subject to legal procedures, s/he has to wait for a deceased donor that would provide a kidney which is called a “legally accepted kidney”. Since there is no governmental control on the market, middlemen have exorbitant gains. Lack of proper punishment for buyers, sellers and middlemen is considered as one of main reasons of not being able to prevent black-marketing. Illegal organizations prefer the countries that have legal loopholes. Turkey was one of the haunts until the re-regulations on the legislation in 2012, since transplantation centers and the competence of transplantation teams are at a high level in Turkey. Standards are as high as they are in the U.S. where the first transplantation surgery was made and that also applies for most of the advanced techniques and systems in transplantation.

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People are dying because of the length of the waiting list while illegal activities keep continuing on the other side owing to the problems in legal regulations. When the regulations are aligned to eliminate the difficulties as in the case of Iran, illegal activities would cease, patients would gain health as well as the money-loss would turn into gain.

Considering the donation system, it is clear that the patient would recuperate (gain), surgical team and hospital would receive their fees (gain) however the donor and his family would have no gains (loss). The only gain of donor is the moral satisfaction from saving the life of somebody else. In most cases, this sort of a motivation is not sufficient. Although Turkey is ranked as the first in terms of living donation rates in the world, it is ranked average regarding deceased kidney donation rates per million capita. It seems impossible to close the gap between supply and demand of kidney as long as the current donation system prevails. At this stage, it is a must that the authorities change their perspective about the donation mechanism.

There are misconceptions about becoming an organ donor. People think that their organs will be taken before death or their medical records could be sold to middlemen and they could be “hunted” in case they legally become donors. Proper and explicit information should be provided to these people that these records are confidential, reserved and their organs cannot be taken before death. On the other hand, in order to eliminate reasons with religious roots, there must be a proper and effective integration between the Presidency of Religious Affairs and the government.

The studies to increase donation rates receive immediate response. Encouraging campaigns by the Ministry of Health in recent years helped increase the donation rates to some extent up to 259% between 2007 and 201433. After the enactment of legal regulations for increasing donation rates that was supported by effective and comprehensive proportional campaigns between 2010 and 2014, an almost 140% donation growth rate was achieved (51.6 ppm as of December, 2013). Even though these results may seem promising, the vast majority of donations comprises living donors and generally close relatives (46.6 ppm by the end of 2013). It is already mentioned that Turkey is ranked as the first in terms living donation rates however deceased kidney donation rates are relatively lower in comparison

33 http://aa.com.tr/tr/saglik/organ-bagisi-kampanyasi-basliyor/207083 126

to rates of European countries (5 ppm)34. The reasonable explanation for the fact that Turkey is well ahead in terms of living donor ratios is that the recipients who cannot find a donor from their close relatives have to wait for a deceased donor in general, yet are not able to receive one. On the other hand deceased donation rate in Turkey is far below than the average of the world. Within this context, studies to increase deceased donation rates should be made.

The tracking system35 of the Ministry of Health covers the entire country in order to effectively track and allocate organs. Even this tracking system governed by regulation comprises some defects; that is the system tracks already registered patients and donors and potential donors cannot be and are not known. At this point, the main responsibility should be borne by the medical personnel who work in intensive care units and/or emergency units. Employees in charge of these critical units, especially doctors, could be trained to persuade the families to donate the organs of their deceased relatives. Doctors and personnel usually avoid asking for organ donation. Regular training is provided to the staff of dialysis and transplantation units by the Ministry of Health on a periodic basis. Attempts regarding this matter would result in increased donation rates. Such kind of a demand does not comprise an illegal characteristic; every attempt will turn out to be a benefit in many forms however it is an encouragement to save lives in particular.

12.5. Encouraging Living Donation

Achieving a decrease in health care expenditures is not the primary objective of health-care executives however resources are limited and optimum allocation is required to maximize health gains. Within this context, renal transplantation reduces lifetime health care costs and increases patient benefits. Ultimately, it is cost-effective when compared to dialysis (Kalo: 2003).

Kidney shortage is a universal problem and waiting times are unbearably long (Freidman: 2006). This shortage cannot be met with donation programs even in developed countries where deceased donation rates are higher than most other countries (Shimanozo: 2007). Living organ donation increases the pool of organ donors and may improve the overall

34For further information please check www.IRODat.org registry reports. 35 For Daily donor tracking system please check: https://organ.saglik.gov.tr/web/ 127

efficiency of transplantation (İsrani et al.: 2005). Vast majority of living donors is of direct donation, i.e. to family members (Kessler and Roth: 2014).

There are reasons because of which many people hesitate or feel leery of becoming a living donor. First of all, being a living donor is frightening for most of the people since living without an organ may cause many problems. However, a missing kidney does significantly affect the quality of life. Apart from heavy-duty employees and sportsmen, living with single kidney does not constitute a problem. “Kidney failure” defines malfunctioning of both kidneys. For this reason, studies for increasing the donation must explicitly explain that there will be no difference about quality of life after donation.

Religious concerns are among the major drawbacks which apply for the vast majority of the Turkish people. “Deceased body must have integrity” is the common consensus. A fatwa made public by the Presidency of Religious Affairs about organ donation which indicates there is not any inconvenience regarding organ donation should be underlined and highlighted by Ministry of Health on all occasions.

Another concern is the lack of trust of people towards the system. Individuals believe that their medical records could be obtained by third parties and used to find a matching donor or tracked. It must be explicitly stated that these records are confidential and only authorized staff have access.

Potential donors are afraid of losing their lives during the surgery. In 2014 there is no recorded death during transplant surgery and only one donor died because of post-surgery complications among 4,263 transplantation. Death risk during this kind of a surgery is less than dying because of a car accident (www.organ.saglik.gov.tr presentation video). Average death ratio in the world is less than 0.1%, which is much more than Turkey’s average. In consideration of this fact it must be clearly explained that death risk during surgery is almost zero.

Detailed and comprehensive explanations covering every risk and gains have to be made during the admission of the donor. Basics and common concepts regarding transplantation and donation are not clear in the minds of individuals, thus it is essential that exact information must be provided to registered donors and their hesitations must be eliminated. An informative briefing would create a domino effect and encourage the registered donors to persuade non-donors (Thiessen et al.: 2013, Parekh et al.: 2008). 128

PART IV: RECOMMENDATIONS

13. AN ALTERNATIVE PROPOSAL FOR KIDNEY DONATION SYSTEM IN TERMS OF SOCIAL WELFARE

The donation systems were examined in Chapter 5. Donation rates in opt-out system countries are much higher in comparison to opt-in applied countries (Shepherd et al.: 2014, p.8) which is related to the indifference of people about the default system. A default opt- out system gives rise to an environment where choices without restrictions are involved (Aysola et al.: 2016). Several studies reveal that modifying the default settings from an opt-in system to an opt-out system increases enrollment rates (Aysola et al.: 2016). Under circumstances where an opt-out system functions properly donation rates are likely to increase. Johnson and Goldstein listed systems of 17 European countries and found that countries which apply an opt-out system have higher donation rates (Johnson and Goldstein: 2003). Greece has low donation rates although an opt-out system is applied however the system is successful in general. An example of the actual success of the system in terms of donation rates is Spain which is the leading country for deceased donation rates more than for 5 years (IRODaT registries and Section 4).

Despite the effectiveness of opt-out system organ shortage cannot be eliminated in almost all of the countries except Iran. The success of Iranian model shows that a monetary incentive for organ donation is effective (for the explanation of Iranian system check Section 5.4.1.1). In regard to this fact, this thesis proposes the following which based on three core items:

i. Opt-out regime ii. Monetary incentive iii. Government monopsony

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Opt-out Regime

The effect of an opt-out regime was explained in the previous chapters. Change in a system from opt-in towards an opt-out regime gives rise to differences in the donation rates. An opt-out regime is generally effective on deceased donation rates. Increase in donation rates from deceased donors also results with an increase in the donation of other organs such as brain, cornea, lung, liver etc. There is a great gap for other organs except kidney; this shortage could only be satisfied through deceased donations, hence donations from a deceased would increase the number of transplants including kidneys. Since a deceased donor theoretically supplies two kidneys at once, it appears to be more effective in terms of transplantable organ supply with respect to living donors.

The approval of the next of kin stands as a major weakness in the application of opt-out regimes that considerably restricts donation rates. At this point, application of opt-out regime strictly becomes important. The resistance of next of kin should be ignored or the family should be persuaded. The family could resist about donation or could sue the hospitals/doctors. Such a resistance and the consecutive organ loss should be borne unless the family is convinced. Well-educated psychologists and psychiatrists for persuading the next of kin are required. The psychological states of the relatives would surely be sensitive therefore these professionals in contact with the next of kin must be proficient in terms of managing issues under such circumstances.

The training of intensive care unit personnel is an important matter regarding the donation of deceased patients since they are directly in touch with the families. The most suitable patients are brain-death patients. Another source of transplantable organs is car accidents with loss of life/lives. People who lose their lives through an accident are potential donors. In case an opt-out regime is in force, no permission is required. It is a race against time to graft an organ and transplant it to a patient. Asking for permission results with the deterioration or death of the organ which make it ineligible for transplantation.

Monetary Incentive

There are more than 60,000 kidney patients and almost 30,000 patients on the waiting list (www.organ.saglik.gov.tr) and this shortage cannot be met with the current system. The vast majority of health expenditures are made for kidney diseases. Almost 5% of total

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health expenditures are directly caused by kidney diseases whereas indirect expenditures amount to 20% (Kidney Disease Control and Prevention Program in Turkey: 2014).

According to the analysis contained herein, the cost of each patient is almost TRY 882,000 (Section 8) while comorbidities are not included intentionally in the calculations. Besides, the sensitivity analysis reveals that a 10% increase in donation rates or a 10% decrease in the number of people on the waiting list or even a 10% increase in the number of transplantations results with an excessive amount of savings in total health expenditures. The replication of the analysis of Becker and Elias indicates that a monetary incentive of almost TRY 12,000 results with a 440% increase in donation rates.

CKD patients die while they are waiting for a proper kidney. The first alternative or the most possible supply of a kidney is their spouses and relatives however although the living donation ratio in Turkey is ranked the highest in the world, it is not sufficient. Unrelated donation is restricted or forbidden by law so the only alternative left is to die unless they find a kidney primarily from a living-related donor. In case a legal organ market is established, altruism would not be that much needed and living-donation rates who are neither spouses nor relatives will increase. Besides, it will convince more families (Cherry: 2005).

It is important to once more note and highlight that this study does not deal with the physiological or moral concerns regarding the issue examined and analyzed through the whole thesis. The main objective is based on the economics of the matter. In the Section12.2 “Economic Analysis of Monetary Analysis” the amount of monetary incentive is examined that is calculated to be very small when compared to the cost of an individual kidney patient. According to the proposal, there must a strict application of the opt-out regime. The resistance of the family must be ignored unless there are no other problems. The family could strictly resist donation or they could sue the hospitals/doctors.

Persuasion of the family is of primary importance. In order to achieve this goal, trained and convincing personnel skillful on human psychology should be employed. The family would be graving thus approaching them would also be a delicate issue. The personnel must be persuasive on the next of kin for giving life to another individual.

Behind the moral and ethical debates, there is a grim reality; a lot of people suffer from kidney disease. The shortage of kidneys yields a substantial cost both for the patients and 131

the government. One major problem about a payment to a donor is legal regulations. Government can easily change the law and can regulate the system. A small amount of a payment (compared to the general costs) to the donor results in a great amount of donations. In the current system, hospitals and surgery teams are paid for their services, patients regain their health where donors get nothing. Besides, donors face the risk of loss of health, quality of life, labor and bear a serious risk of death. The monetary incentive estimation herein is the provision of losses but not the value of kidney at all. This point is important since the calculation encompasses a “monetary incentive” for kidney donation itself. The cost of a kidney could differ according to buyers and/or sellers. The amount could increase up until equilibrium between supply and demand is achieved.

This payment should not be considered as s commodification of the human body and is only for covering the expenses. Besides, a little endowment could be useful for increasing the donation rates. On the other hand people are trying to buy or sell kidneys on the black market. Some people are willing to sell their kidneys. Opponents argue that if there is a payment to the donor, only poor people will be willing to sell their kidneys. But legal regulations are not sufficient to restrain this transaction. Buyers and sellers do meet somehow. The worst part about this gathering is the lack of medical care for the both the recipient and the donor. Donors are treated as if they are commodities traded and which could be disposed of. There is no respect to human integrity and since this is an illegal operation, the organizers are attentive in managing such operations as quickly and quietly as possible.

The second problem is about the middlemen those who find the donor and the recipient, and make the largest portion of the profit out of this activity. It is a fact that the amount that the donor receives and the patients pays differ considerably which is attributed to the hospital and transportation costs and the risk payment of the middlemen; in most of the black market transplantations, donors are forced to pay their medical expenses and the surgery is generally made under improper conditions.

Government Monopsony

The urgency and benefits regarding increases in donation rates are explained and payment to donors is criticized. A monetary incentive can increase the donation rates however

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middlemen can take advantage of the system therefore a governmental regulation for organizing the allocation and control the amount and technical infrastructure for incentive is required. Governmental regulations have to be in force in order to make the proper allocation for recipients and potential donors. The allocation system in Turkey is sound (details about the allocation system are examined in Chapter 8) however the system could be converted into a paid-system. Governmental control would be on regulating the incentive mechanism where a regulated mechanism would contribute suppressing the black-market (abuses), guarantee the payment to donor and ensure medical care for recipients and donors. In total; an organized incentive mechanism would be more productive and feasible.

Increase in the number of transplantations with the introduction of a monetary incentive would have primary and secondary benefits. Medical care before and after the surgery for donors and recipients, direct and indirect taxes, decrease in the number of people on the waiting-list, decrease in insurance costs, decrease in ongoing dialysis costs for patients are considered as the primary benefits while the reduction of the number of cases with comorbidities, decrease in the waiting time on the waiting list, less days of dialysis, less suffering of beloved ones and suppression of the black-market are regarded as the secondary benefits. An alternative proposal of governmental regulations for an incentive system is detailed in the next section.

However, as long as there is a governmental intervention, there would be laws and regulations for this intervention. Matas and 50 of his colleagues (including Satel, Reed, Goodwin and Levy) organized a meeting in Philippines in 2011 and signed a meeting report (Matas: 2012) that proposes a solution for a regulated system of incentives and limitation of disincentives and is considered as the first comprehensive legal solution proposal for kidney shortage according to which government monopsony must comprise protection, regulation, oversight and transparency.

The main advantage of government monopsony is the protection it provides. As it is already in force, the government can compel transplant centers to fully inform donors regarding the risks, incentive mechanism and benefits of becoming a donor. Since government monopsony would create the regulations, related policies for follow-up, correction of irregularities and determination of outcomes would be controlled by the

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government. The key concern is transparency that it should be observable by international organizations.

Actually there are drawbacks affecting the decision making of potential donors. Donors have concerns about short or long term losses and burdens of becoming a donor. In addition to the actual losses the donor would inevitably have troubles about insurance policies. The donor’s premium would increase and s/he would have some more troubles with insurance companies. Thus governmental incentives should focus on this secondary problem.

Religious concerns constitute another issue. People believe that human integrity must be maintained after death. Regarding such concerns, Presidency of Religious Affairs published a fatwa36 about organ donation which could help eliminate this matter.

Potential donors have concerns about the surgeons and believe in the possibility of being harvested before death. Surgeons can intentionally lead to the death of a donor if his/her organs are compatible to any other patient. There are some examples given in Chapter 7. Examples from Brazil, India and Argentina reported by Scheper-Hughes (Scheper-Hughes: 2002, pp: 69-71) are meaningful in this sense. However such a practice cannot be generalized for all surgeons since (i) doctors have to have priority in keeping the health of a patient (ii) the medical records of the patients are confidential. When a person is registered as a donor, s/he is given a donor-card which does not contain any medical information except blood type. On the other hand, if organ smugglers seek for proper donors it is enough to obtain these records from a hospital or a health organization through illegal channels.

If donations are considered at a satisfactory level, potential donors could step back from becoming donors which is called the “crowding-out effect” (Epstein: 2008, p.18). The reason for this consideration is based on the outcome of declined ratios upon payment made for blood donations in England (Titmuss: [1971]1997). Recent studies show that crowding-out effect has a limited effect on the donation rates, moreover live donations do

36 According to a fatwa given by Presidency of High Board of Religious Affairs in March 2013: the grafted person has to give permission before death or next of kin’s approval has to be taken, no charge for grafted organ or tissue and the patient must consent for the transplantation. Also, Consultation and Religious Works Investigation Board permitted blood and eye/cornea transplantation in the Resolution 492 in September 1960. High Council for Religious Affairs added the permission for heart transplantation on January 19th, 1968. For more information: http://www.haber7.com/guncel/haber/997082-iste-diyanetin-organ-nakli-fetvasi 134

not pose the same threat to deceased donations (Beard et al.: 2009). Since organ donation is not sufficient and there is a huge gap between supply and demand of kidney, occurrence of this problem would take a long time. The circumstances of donating blood and donating a kidney (or an organ) are not similar and the results as well as the benefits are not in the same category. Blood is re-produced, it is easy to find and donation system of blood is settled. Donating a kidney is complicated, irreversible and is a critical decision. Donor becomes healthier upon blood donation however this is not the case when a kidney is donated. Studies and researches on volunteerism and payment show that the effect of volunteerism is more than the effect of payment (Frey and Gotte: 1999, Gneezy and Rustichini: 2000). Beard et al. (2012) found that payment would cause “substitution effect” which could be replaced as crowding out effect. They found significant substitution between deceased and living donor transplants. According to their calculation there is less prospect of reducing waiting list growth rates for deceased kidney donation than is generally supposed (Beard et al.: 2012, p. 264). Among these arguments, it is assumed that “whatever financial incentives exist, siblings and parents will continue to donate to loved ones” (Rothman and Rothman: 2006). DeJong et al. found that a financial incentive has a very little (only 6%) effect on their likelihood of donating a family member’s organs (DeJong et al.: 1995, p.468).

13.1. Governmental Regulations for Incentive Systems

The governmental regulations comprise some dynamics that organize and increase the effectiveness of an incentive mechanism. Key factors of government monopsony are as follows:

a) An incentive system shall have a legal and regulatory framework for the process. The boundary and limits of the system shall be well-defined within this framework. b) The full-organization shall be transparent and kept available for governmental and international oversight. In general, supervisory deficiencies result with question marks and potential donors lose their faith in the system. Within this context, international persuasiveness is important to convince citizens. c) The incentive shall be provided either by the government or by a government- recognized third party. If the system is well-organized and transparent, recipients or benefactors would fund the charities. A direct payment from the recipient to the

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donor is not a must condition. This payment could be made by a charity organization that is supported by government or NGO’s. This would help reducing the number of wait-listed people. Charity organizations could become a major actor in funding health care for poor people (Cherry: 2005). d) The allocation system could be well-defined and well-organized by a single entity. The recipient shall be able to make a direct payment to the system so that every citizen on the list shall have an opportunity to be transplanted. The waiting-list must be fair and allocation would be based on an equitable manner. e) A strict and operative plan for the administration of oversight for evaluation, acceptance, allocation and provision of incentive to the donor shall be organized. This organization is an important component of the system. f) Donation shall be anonymous. Donor and recipient contact shall not be allowed in order to sustain the stability of the system. Disclosure of the donor could result in a direct payment form the patient to the donor. g) There shall be a unique organization for the allocation and payment of the incentive. h) The regulations shall impose sufficient punishment. Every organization involves human-factor and every human-based organization is open to abuse. Therefore, an effective punishment system would be deterrent in terms of preventing abuses (Matas: 2012).

In addition to these regulations, there are some other requirements those should be integrated with the regulations. Donor must be well-informed about the risks and should understand the concept of the operation. There should be a full clearance for donor’s acceptance. It must be well-defined and transparent and monitoring process of the donor must be clear.

The incentive amount shall be fixed so that every donation would have equal value. Otherwise, there could be a preference in favor of a donor. The program shall be limited to the third party. This kind of a limit shall ensure the stability of the allocation. As a result the donation shall stand as anonymous and the likely contact of the recipient and donor shall be eliminated. Donor shall be informed about after-transplantation requirements which consist of follow-up requirements and home-care needs.

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The numbers of deceased donors, living donors, wait-listed people, transplantations and waiting time for a deceased donor should be publicly announced. Besides, academic studies about the outcomes of living and deceased donations, benefits and costs and impact of incentivized donations for the donor and the patient should be published.

The Iranian system is a solid example of government monopsony. Iranian system proves that governmental regulations minimize the risks and costs of transplantation. A regulated system also prevents both donors and recipients from the abuses of the black-market, stops wealth transfer and guarantees the medical care for both parties.

Some of the researchers are against monetary incentive for organ donation. There are various determinants for opponents. One of the reasons is that such policies will decrease the donation rates because people will find the policies repulsive (Evans: 2003). Deck and Kimbrough made laboratory experiments about the effect of market incentives at crowd- out charitable giving. They reached the following two main findings:

“Main finding 1: Introducing a market does not crowd-out charitable giving. Instead, introducing a market leads to an increase in the supply of available assets for transfer. Main finding 2: The introduction of a market encourages the relatively poor to supply assets while the decisions of the relatively wealthy are not affected by the introduction of a market. Thus, the increase in supply observed with the introduction of a market is driven by actions of the relatively poor” (Deck and Kimbrough: 2013, pp. 20-21).

One other reason is the fear of economic coercion of the poor. There are four main problems with the economic coercion:

i. The ethicist substitutes his/her values for those of the individuals involved in transaction. ii. The market-clearing price of organs of deceased donors at financial incentive that overrides fundamental religious or moral beliefs. iii. For the selection of policy options of the degree of coercion involved, consideration of the market system not in isolation but in a comparison to existing system. iv. Economically coercive system must take responsibility for the high price extracted under the current policy to avoid such coercion (Barnett et al.: 1993)

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Another concern regarding monetary incentive is that organ market would restrict accessibility to transplants for the poor. Use of the market system for procuring organs does not necessarily mean using the system for allocation (Evans: 2003).

Organ markets would comprise an adverse effect of the incentive on physicians to maintain adequate care for critically ill patients.

Another argument with regard to the donor is about organ selling. Moniruzzaman (2012) and Chapman (2008) indicated that people who sell kidneys turn back into poverty quickly. Delmonico et al. oppose financial neutral acts for living and deceased organ donation. They uphold that offering financial incentives is no different than paying for organs and claim that financial incentives are fundamentally wrong (Delmonico et al.: 2015).

13.2. Evaluation of Applications around the World

Almost every country has its own legal Acts about punishing and prohibiting organ trafficking. Organ transplantation has 50 years of a history so most of these Acts of countries are relatively new. The following table lists the penalties imposed by legal regulations of some countries in terms of fines and imprisonments. Most of the imprisonments are either insufficient or not deterrent; therefore some of these countries re- regulated their Acts in time. According to the list below, organ trafficking is subject to fine and imprisonment in most countries while in some of the countries only imprisonment or payment of a fine are the penal sanctions imposed.

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Table 16: The list of penalties imposed in countries. Source: Bilgel (2011)

Country Fine Imprisonment Australia AUD 400-500 3-6 months Austria EUR 2,200 Belgium EUR 1,000-10,000 3-12 months Bulgaria BGN 100,000-500,000 4-12 years Canada CAD 100,000 up to 1 Year Czech Rep. 2-8 Years Estonia up to 1 year France EUR 100,000 7 years Georgia prohibition but no specific criminal sanction Germany 1-5 years Greece at least 1 Year Hong-Kong HKD 10,000-25,000 at least 1 Year Iceland Up to 3 Years India INR 10,000-20,000 2-7 years Ireland no legal provisions Italy 2-12 years Japan JPY 500 million equivalent imprisonment Kuwait KWD 3,000 Dinars Up to 3 Years Lebanon 1-12 months Luxembourg 1 month-3 years Morocco MAD 50,000-100,000 2-5 years Netherlands EUR 11,250 1 year New Zealand NZD 50,000 up to 1 Year Pakistan PKR 1 million up to 10 years Poland EUR 1,500 3-10 years Romania 3-7 years Singapore SGD 100,000 up to 10 years South Africa up to 5 years Switzerland CHF 100,000-500,000 6 months UK up to 3 years US USD 50,000 up to 5 years

According to the list, for most of the countries, imprisonment is less than three years and/or fine is not enough to deter compared with the gains of middlemen. The sanctions in poor countries are not sufficient. Black-market is mainly settled in undeveloped countries for the source of living kidney donors and settled in rich countries for potential buyers. Insufficient Acts shed light on smuggling.

Shepherd et al. made a panel study on opt-in and opt-out systems which are listed in IRODat registry (Shepherd et al.: 2014). According to their analysis there are 48 countries;

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23 of them employ an opt-in system and the rest employ an opt-out system. There are 15 countries in the Eurozone employing an opt-out system.

Table 17: List of donation systems around the world

Country Opt-in Opt-out Country Opt-in Opt-out Argentina x Italy x Australia x Japan x Austria x Latvia x Belarus x Lebanon x Belgium x Lithuania x Brazil x Malaysia x Bulgaria x Mexico x Canada x Netherlands x Columbia x Panama x Costa Rica x Poland x Croatia x Portugal x Cuba x Puerto Rico x Czech Republic x Romania x Denmark x Russia x Ecuador x Singapore x Finland x Slovak Republic x France x Spain x Germany x Sweden x Greece x Taiwan x Guatemala x Tunisia x Hong Kong x Turkey x Hungary x U.K. x Republic of Ireland x U.S.A. x Israel x Venezuela x

Some countries are not included in the analysis owing to the fact(s) that (i) there is not an active donor program (Armenia, Azerbaijan, Bangladesh, Egypt, El Salvador, Georgia, India, Libya, Luxembourg, Macedonia), (ii) population is less than two millions (Cyprus, Estonia, Malta, Qatar), (iii) high level of organ trafficking is prevalent (Moldova, Ukraine), (iv) a mixed structure of civil and common laws (Norway, Philippines, South Africa, South Korea) and/or (v) large number of transplants occurring abroad (Saudi Arabia) (Shepherd et al.: 2014).

Researches show that opt-out regimes have more donation rates than opt-in regimes (Shepherd et al.: 2014, Anderson: 2015). Although there is crowding-out of approximately

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0.7%, there is a considerable difference, in the range of 5% to 7%, between these systems (Anderson: 2015). While deceased donation rates are higher in opt-out system, living donation rates are slightly higher in opt-in regime in comparison to opt-out. One of the effective reasons of high deceased donation rates is the number of transplantable organs which is attributed to the fact that when a deceased body is donated, rest of all organs are also eligible for transplantation (heart, lung, tissue, bone marrow, skin etc.) rather than only kidney and liver.

There are some other reasons those affect the donation rates which mainly are number of beds in hospitals, GDP, social structure of the nation, number of intensive care beds, procurement procedure, consent type and religion. Although opt-out system increases the donation rates, it does not yield the same outcome in every country as in the case of Greece, where donation rates are very very low (6% pmp) (IRODat registry: 2014). Some countries try different methods for increasing the transplantation rates. For example, Israel makes a payment to its ESRD patient citizens up to $50,000 for transplantation. Donor could be a foreigner or the recipient could be transplanted abroad (Jotkowitz: 2008). Georgian government makes a $9 discount over an agreement to become a donor (Calandrillo: 2004, p.113). In the U.S. Wisconsin was the first state offering a tax deduction to living kidney donors for covering expenses incurred from donation in 2004. Afterwards Indiana, New York and New Jersey adopted legislations to receive tax deductions for allowing donors, and New Mexico and Pennsylvania are evaluating to put into force similar legislative models (Steinbuch: 2008, p.1557). Opt-out system employed in New Zealand is much stricter than opt-out systems in other countries. However the most effective opt-out system application is in Spain. The deceased donation rates in Spain are ranked the highest in the world (IRODat registries).

On the other hand, there is a major difference in the system employed in Iran which is known as the Iranian System that comprises a distinctive feature. In order to observe the effectiveness of a monetary incentive, Iran is the best example where the donor cannot donate his/her kidney to a foreign country citizen. Payment to the donor is organized by a non-governmental organization which is authorized and supported by the government. As a result, the number of the people on waiting list decreased drastically and dramatically upon the application of this system. The fact is, there is no one in queue and the waiting time for a proper kidney is very short.

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13.3 Discussion

Kidney disease is a long lasting and incurable disease not easily diagnosed in earlier stages. It is irreversible however delaying the effects of the disease is possible with the proper treatment. The patients at stage 3 to stage 5 need medical intervention that starts with dialysis until ESRD. Kidney transplantation and dialysis are the only treatments of ESRD. ESRD patients need transplantation and required kidneys are available through a deceased or a living donor who can be a spouse or next of kin by law. This is the exact point where the gap between supply and demand of transplantable kidneys starts to grow.

The majority of the patients are unable to find living donors therefore they join the waiting-list pool for a deceased donor organ (Bertsimas et al.: 2013). The picture is the same In Turkey, that is the number of dialysis and ESRD patients are increasing while the rate of increase in the number of transplantations is not coequal. Besides cost of dialysis patients is increasing and does not seem to be stabilized in time.

The governmental Acts are insufficient to close the gap. The proposal in the previous section could be a solution for kidney shortage. Most of the proposals involve deceased donation. Proposals on favor of allowing living donor kidney sales are increasingly published in prestigious medical journals (Koplin: 2014).

Most of the researchers agree upon the benefits of compensation of kidney donors. Wilkinson (2011) and Rothman and Rothman (2006) detailed the theoretical background about the sale and cost of human organs. Gaston et al., (2006) proposed limiting financial disincentives in living organ donation which could be a rational solution to the kidney shortage. Martin and White (2015) examined the necessity of financial incentives for living kidney donors. Israni et al., (2005) criticized the incentive models to increase living kidney donation. Barnett et al., (2001) analyzed the efficient and equitable free market in kidneys. Kessler and Roth (2014) made an evaluation for increasing the number of organs for transplantation. Howard (2007) also criticized the reform proposed for producing organ donors.

Matas and Schnitzler (2004) made a cost-effectiveness analysis regarding payment for living donor kidneys. Evans (2003) made a statistical estimation for different types of financial incentive policies. Held et al. (2015) made a cost-benefit analysis of government

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compensation of kidney donors including increase in life years from receiving a transplant and present value of benefits and costs for all kidney recipients. Barnieh et al. (2013) made cost-effectiveness and sensitivity analysis of using a payment system to increase living donor kidneys. Byrne and Thompson (2001) proposed a model for monetary incentives for deceased organ donation.

Leider and Roth (2010) argue the rights of legal authorities about disapproving the sale for kidneys. Martin and White (2014) also argue the risk, regulation and financial incentives for living kidney donation. Hoeyer et al. (2013) made a meta-analysis for public attitudes of financial incentive models for organs. Evans (1993) analyzed the organ procurement expenditures and the role of financial incentives. Matas et al. organized a working group on incentives for living donation in Minnesota (2011) and proposed standards for an internationally accepted system.

Some academicians like Mayrhofer-Reinhartshuber et al. (2006), Gordon et al. (2015) run a questionnaire survey about the effects of financial incentives. A solid calculation for incentive amount for living and deceased donation was given by Becker and Elias (2007). Every suggestion about monetary incentive, be it either a supporter or an opponent, has an intellectual background and every proposal/opinion has a reasonable explanation. Nonetheless there is a reality which is, people are dying while waiting for a transplantable organ. Amount of kidney patients are increasing but donation rates do not considerably change in favor (IRODaT registries). There are medical and technological advancements however they have not found a permanent solution for organ shortage. Medical expenses are increasing related to the increase in patients and prolonged waiting list.

The cost-benefit analysis of one patient who had a transplant surgery after 5 years of dialysis without comorbidities is made in this thesis. Primary costs are included (lodging, transportation, hospitalization, costs of recovery, labor-loss etc.) and secondary costs (comorbidities, suffer from illness, losses of next of kin, multiplier effects of illness etc.) are excluded. According to this analysis, cost of each patient is calculated to be TRY 882,330. Since 5% of total health expenditures are made for kidney diseases, every transplantation surgery will lead to savings in health expenditures. Thus a sensitivity analysis with the following is made:

a. Increase in the number of donors,

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b. Increase in the number of transplantations, c. Decrease in number of patients on the waiting list.

The analysis shows that every positive action makes significant change in health expenditures. Actual governmental Acts are not sufficient to give rise to a difference in donation. Kidney donation system is based on altruism and in Turkey most of the altruistic donations are from living related donors. Turkey is the leading country in terms of living kidney donation in the world yet donation of other transplantable organs is not increasing because of low deceased donation rates. In consideration of these facts, an alternative donation system based on the following three items is proposed:

1. Opt-out Regime, 2. Monetary Incentive, 3. Government Monopsony.

The effect of each item was examined in light of the academic literature. Governmental regulations have to cover some basic aspects including protection, regulation, oversight and transparency which are explained in Chapter 9.

Monetary incentive is the most important item in the proposal. The subject is mentioned and discussed in various sections of this thesis. In terms of benefits, an acceptable amount of a payment has to be made as in the form of a monetary incentive. There are different variables involved in the calculation of the monetary amount, which is theoretically based on the calculation of Becker and Elias (2007). The determinants of the analysis in this thesis are:

i. Value of Statistical Life ii. Death Risk iii. Quality of Life iv. Value of Time

Accordingly, a reasonable amount for the monetary incentive is calculated to be TRY 8,638 and obviously differs in relation to the value of statistical life. Thus, a sensitivity analysis with VSL is made which reveals that the amount varies between TRY 5,300 and TRY 12,000 while change in transplantation varies between 443% and 527%. This incentive is effective in increasing kidney donation.

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Black-market appears to desperate ESRD patients as an alternative. Despite it is illegal, black-market is a promising option to find a kidney for wealthy patients. It emerges from the demand and in general is settled in poor and/or undeveloped countries. Most of the sellers are citizens of poor countries. This demand stirs up organ trafficking and transplant tourism. All aspects of black-market and transplant tourism are already discussed in Chapter 7.

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14. CONCLUSION

Since the very early times that kidney transplantation has become available, numerous articles regarding the issue have flooded the literature. The medical dimension of this matter is of concern of medical professionals, surgeons, physicians etc. where the economic and social aspects have become an attractive issue of research for social scientists. Various proposals were made and different systems were employed in order to satisfy the kidney demand that has grown into a huge amount since then. In line with the recommendations and decisions of WHO, most of the countries in the world, in addition to the member states, banned organ trading and envisaged supplying the kidney demand through (increasing) donations. However, the systems employed have not contributed to satisfying the needed number of kidneys and the gap between supply and demand kept growing. This thesis examines the recommendations and proposed systems for closing this gap mentioned in the preceding sentence. The economic dimension of the issue is of primary concern while the moral, ethical and social aspects are beyond the scope of this study and hence are not examined nor discussed.

Various methods and proposals for increasing the rate of kidney donations can be found in numerous academic studies. Among the many proposed, a system involving monetary incentive appears to be the most effective since such was previously employed by Iran with serious positive outcomes which is the basis for the academic interest and attention. Within this context, there are numerous studies about the amount of this monetary incentive, the method of its assessment and the limit value that potential donors would be eager. Basically, payment of the losses of the potential donors calculated through questionnaires and cost-benefit analyses is proposed. The minimum value of a monetary incentive that should be paid in Turkey is calculated in this thesis on the basis of the losses of a donor. Calculation of a monetary incentive does not intend to commodify the human body but is rather considered as a compensation for the losses of a donor. The amount calculated is noteworthy and quite meaningful inasmuch as it is more or less the same with the price of a kidney in the black market.

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On the basis of the calculated monetary value, the study involves a sensitivity analysis using VSL in order to assess the percent change in the number of kidneys donated under the effect of an increase in the amount of the monetary incentive which in turn reveals that relatively small (incremental) changes in the monetary incentive value lead to a far better increase in donations and the results indicate that a monetary incentive system would prove effectual.

Studies on the costs of dialysis and transplant patients are abundant in the literature and many others are available those are based on different criteria for various countries. Results of some of the mentioned studies are listed for convenience. The most recent study on this issue in Turkey is based on the Markov Model and does not comprise real data. The greatest problem in making such a study is the difficulty in reaching and obtaining real data. Analyzing the kidney donation costs for both deceased and living donors together with the costs of the recipient, this thesis calculates the total transplant cost based on real data provided by Atatürk Education and Research Hospital, Ankara. The analysis calculates the costs of items such as medication, medical equipment, examination and follow-up which are in concern before, during and after the transplant surgery as well as the unit costs of the surgery team. Comorbidities in kidney disease are ignored and not considered in the calculations since they vary depending on each patient.

One other contribution of this thesis is the cost-benefit analysis of a transplant patient versus a dialysis patient. The analysis is based on the fact that a transplant patient has a lifetime of 8 years longer than that of a dialysis patient on average and the calculations are made regarding this difference. The results indicate to a TRY 1,100,000 gain per patient. Losses of the dialysis patient and the donor and the gains through transplantation are considered throughout the calculations. Using the results of the study, a sensitivity analysis is made which is based on the percent changes in increased numbers of donors, increased numbers of transplantation surgeries and decreased number of wait-listed patients. The economic gains of the decrease in the number of patients obtained through the sensitivity analysis are calculated.

The importance and the benefits of monetary incentive is heavily discussed in the literature, however the means and medium of such monetary incentive and related legal regulations are topics of different studies. Nevertheless, the content of legal regulations and the management as well as the method of payment of a monetary incentive are examined in 147

this study so as to provide a guide for rule makers and authorities on the basis of the Minnesota Declaration.

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16. APPENDICES

Appendix 1: Details of Calculations

Statistical value of life:

Statistical value of life is taken from WHO Eurozone 2011 data: 2.487.283 Euro.

Since the data and calculations are made 2016, conversion with regard to purchasing power parity. Therefore in 2016;

$1 = €0.774230

€ 1= $1, 2916

$1 = TRY 1.309846 (According to OECD 2009-2016 data)37

Then; 2,487,283 x 1. 2916 x 1.309846 = TRY 4,207,978.

Minimum Value: 1,243,642 x 1. 2916 x 1.309846 = TRY 2,103,990

Maximum Value: 3.730.925 x 1. 2916 x 1.309846 = TRY 6,311,968

Death risk of donor during or after the operation related to complication(s):

1/4263 = 0.0235 %

Monetary equivalent of death risk: TRY 4,207,978 x 0.0235 % = TRY 989 ……………… (1)

Monetary equivalent of workforce loss:

Minimum civil servant salary (2016) = TRY 2,151

Healing period is about 4 weeks, so monetary equivalent of workforce loss:

2151 푥 12 푥 4 = 푇푅푌 1,985.5 ……………………………………………………………… 52 (2)

37 The statistics data is taken from OECD. For the detailed PPP table please refer to: http://stats.oecd.org/Index.aspx?datasetcode=SNA_TABLE4 178

Monetary equivalent of QALY (Quality Adjusted Life Years):

The ratio calculated by Becker-Elias: 0.0014985

4,207,978 x 0.0014985 = TRY 6,306………………………………………………….. (3)

The total value of monetary incentive:

(1) + (2) + (3) = TRY 9,280

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Appendix 2: Briefing about Data Collection and Gathering

The main factor for making an analysis about the cost of dialysis and transplantation is to obtain reliable and analytic data. There are some predictions for these costs by using Markov model and/or the standard payment of the government insurance system. However these are either irrational or very low depending on the use of side components. In general, such calculations are based on the HAN data which do not reflect actual figures. Therefore the results of such studies are disputed.

Reaching reliable and official any data is not easy in Turkey. Transplantation and hemodialysis costs were asked from various institutions. Atatürk Education and Research Hospital is the first among many other sources of data. The hospital has a dialysis center and is fully capable of conducting transplantation surgeries. In 2015, total number of transplantation operations is 25 where there were foreigners among the patients.. Although Yıldırım Beyazıt University has an agreement with this hospital, that is; the hospital is linked to the university. Obtaining reliable and usable raw data took more than 3 months where in the meantime more than 20 different authorities and official were contacted in person or writing.. After-transplantation data would rather have been preferable however it has not been possible to obtain such data. The Güven Hospital which is a privately held hospital does also perform both transplantation surgeries and hemodialysis nevertheless refuses to provide data stating that the data is classified. One other hospital refused to share hemodialysis costs since the unit in concern was already closed. Ankara Research Hospital which is a state hospital requires permission which is not easy to get. At the beginning of the evaluation process of this thesis, data was also requested from the Social Security Institution. It took almost 5 months that application for data was refused and therefore, the main data source had been lost. The only and solid data is the data of HAN however patient-care information for after-transplantation costs is not available, which could have been useful for analyzing the after surgery costs for patient and donor. On the other hand, legal regulations are very strict and this kind of information is of personnel integrity. Although it was warranted that the use of such data will be limited to academic research purposes and that the receipts could be provided as anonymous, the institutions refused sharing data on the bases mentioned.

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Appendix 3: Calculation Data Set

The details of the drugs and operations used for transplant patients and donors can be taken from the author upon request. The data are included in the CD attached.

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Appendix 4: Curriculum Vitae

YAVUZ DEMİRDÖĞEN

CONTACT INFORMATION

Name: Yavuz Demirdöğen

Address: Yıldırım Beyazıt University, Social Sciences Faculty, Çubuk

City, State: Ankara, Turkey

Cell Phone: +9 0 544 712 80 70

Email: [email protected]

MARITAL STATUS

Married, 2 children.

EDUCATION

 Graduate Institution, City, State: Yıldırım Beyazıt University, Ankara, Turkey

Degree, Major: 3,44 / 5,00

Date of Graduation: April, 2017

Dissertation: Cost-Benefit Analysis of Kidney Donation Systems and an Alternative System Proposal for Turkey

 Graduate Institution, City, State: İnönü University, Malatya, Turkey

Degree, Major: 3,81 / 4,00

Date of Graduation: June, 2011

Thesis: Game Theory Approach on Public Auctions

 Graduate Institution, City, State: Middle East Technical University, Art & Science Faculty, Department of Mathematics Ankara, Turkey

182

Degree, Major: 2,02 / 400

Date of Graduation: September, 1999

EMPLOYMENT HISTORY

August, 2011 - …: Yıldırım Beyazıt University, Social Sciences Faculty, Department of Economics, Instructor

2009 – 2011 : Bingöl University. Economic and Administrative Sciences, Department of Business Administration, Research Assistant

2007 – 2009 : Final Dersanesi, Mathematics Teacher

2003 – 2007 : Gelişim Dersanesi, Mathematics Teacher, Co-founder

1999 – 2003 : Final Dersanesi, Mathematics Teacher

1996 – 1999 : Açı Dersanesi, Geometry Teacher

PUBLICATIONS

DEMİRDÖĞEN Yavuz, “Costs of Kidney Transplantation in Comparison to Organ Prices in Black Market”, 3rd International Annual Meeting of Sosyoekonomi Society, April 28-29, Ankara, 2017.

DEMİRDÖĞEN Yavuz, How does Incentive affect Donation Rates: Turkey Case, Sarajevo Journal of Social Sciences; Faculty of Business and Administration; International University of Sarajevo; ISJSS; ISSN 2303-7105, Vol. 2, No. 3, 2016

Y. BULUT, DEMİRDÖĞEN Yavuz, On Conditional Distributions of Order Statistics, February, 2011 (http://pphmj.com/abstract/5661.htm)

DEMİRDÖĞEN Yavuz, SÖYLER Hasan, “Game Theory Approach on Public Auctions”, 12th International Econometrics, Operation Research and Statistics Symposium, Denizli, 26-29 May, 2010

DEMİRDÖĞEN Yavuz, BAYDAŞ Abdulvahap, “Contributions of Universities to the City and Expectations of Students from the City: Bingöl Sample”, Bingöl Symposium, 17- 18 September 2010

183

DEMİRDÖĞEN Yavuz, BAYDAŞ Abdulvahap, “The Perception of CRM from Banking Clients: Bingöl City Sample”, Bingöl Symposium, 17-18 September 2010

PRESENTATIONS

DEMİRDÖĞEN Yavuz, SÖYLER Hasan, “Game Theory Approach on Public Auctions”, 12th International Econometrics, Operation Research and Statistics Symposium, Denizli, 26-29 May, 2010

DEMİRDÖĞEN Yavuz, BAYDAŞ Abdulvahap, “Contributions of Universities to the City and Expectations of Students from the City: Bingöl Sample”, Bingöl Symposium, 17- 18 September 2010

DEMİRDÖĞEN Yavuz, BAYDAŞ Abdulvahap, “The Perception of CRM from Banking Clients: Bingöl City Sample”, Bingöl Symposium, 17-18 September 2010

DEMİRDÖĞEN Yavuz, “The Quantity of Monetary Incentive and Effect on Kidney Donation”, 2nd Sarajevo International Conference on Social Sciences, May 17-20, 2016

LANGUAGE

Fluent in English (800/900 from TOEIC), (82,5/100 from YÖKDİL)

OTHER

Erasmus+ Independent External Evaluator for KA1 and KA2 Projects (2015-2016)

Erasmus+ Teaching Staff Mobility, Technical University of Kösice, Slovakia, June 2015

Erasmus Leonardo da Vinci Transfer of Information (ToI) Project: European Safety Standards in Industrial Automation for SMEs (SafeSME) 2010 (Project Manager)

TRANSLATIONS

Bodie, Kane, Marcus, Essential of Investments, Chapter 16 and 17 (Nobel Publications)

Venardos Angelo M., Current Issues in Islamic Banking and Finance, Chapter 7 (Nobel Publications)

ISRA, Islamic Financial System: Principles and Operations, Chapter 12 (Nobel Publications)

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Appendix 5: Turkish Summary

Son yüzyılda dünya %80-90 oranında başarılı ameliyat ve organ nakli gelişmelerine şahitlik etmiştir. Fakat ihtiyaç duyulan nakledilebilir organ miktarıyla nakil yapılan organ miktarı arasında büyük bir fark bulunmaktadır. Ekonomik olarak bu cümleyi ele alırsak, nakledilebilir organın arz ve talebi arasında arz lehine büyük bir fark olduğu gerçekliği ortadadır. Arz için tek kaynak insan bedenidir. Nakil yapılan organlar içerisinde böbrek en büyük paya sahiptir. Dünyada organ arzını sağlayan tek kaynak organ bağışıdır. Son birkaç on yılda açık dramatik şekilde büyümekte ve uygulanan sistemler nakledilebilir organlar için arz ve talebi, özellikle bu tezin merkezi olan böbrek açığını dengeleyememektedir. Türkiye ile ilgili kesin bilgilere dayalı maliyet-fayda analizi bulunmamaktadır. Bu tez öncelikli olarak diyaliz ve böbrek nakil maliyetlerini kıyaslamakta ve bağış miktarlarının artırılmasıyla elde edilecek faydalara odaklanmaktadır. Bağışlardaki artışlarda elde edilecek ekonomik kazançlarla ilgili duyarlılık analizi yapılmıştır. Etik endişelerin dışında tazmin edilmiş böbrek bağışı betimlenmiştir. Bu teşvik böbreğin ticarileştirilmesi değil donörün kayıpları üzerine odaklanmıştır. Parasal teşvik miktarı özellikle Hayatın İstatistiki Değer’inden etkilenmektedir. Bir başka duyarlılık analizi de Hayatın İstatistiki Değer’inde değişikliğin parasal teşvik miktarına etkisi üzerine yapılmıştır.

Bu çalışma sırasında karşılaşılan birçok zorluğun yanında paydaşlar olan hastaneler, diğer organizasyonlar ve Sosyal Güvenlik Kurumundan veri elde etmek olmuştur. Bu kurumlardan yapılan her türlü resmi ve istatistiki veri talebi reddedilmiş ve sadece bir hastaneden 3,5 aylık gayret sonucunda veri elde edilebilmiştir. SGK 7 aylık bekleme sonunda “kişisel bilgilerin gizliliği” sebebiyle veri vermeyi reddetmiştir. Elde edilen ham veriler üzerine detaylıca çalışılmış ve gerekli hesaplamalar yapılarak ihtiyaç duyulan sonuçlara ulaşılmıştır.

Bu çalışmadaki değişkenlerle ilgili metodolojik bir çalışma bulunamamıştır. Hesaplamaları değiştirebilecek yaş, cinsiyet, sosyal statü, böbrek hastalığının öncesi ve sonrası ile ilgili yan hastalıklar gibi birçok değişken bulunmaktadır. Hesaplamalar normal bir hastanede yapılan mevta ve canlı donörden nakli esas almış, diğer değişkenleri hesap dışında bırakmıştır.

Bu çalışmanın amacı böbrek naklinin maliyet-fayda analizini yaparak literatüre katkı sağlamaktır. Hali hazırda bir sistem bulunmaktadır fakat bu sistem uzayan bekleme

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listesini azaltmak konusunda yetersizdir. Bu sebeple tez böbrek bağış ve nakil oranlarını artıracak alternatif sistem önermektedir. Önerilen sistem aynı zamanda fakir insanları sömüren karaborsayı baskılayacaktır.

Sağlık ve medikal teknolojideki ilerlemeler insan hayatının uzatılmasını amaçlamaktadır. 1970lerden sonra immunosupresiflerin keşfini takiben organ nakillerinin başarı oranı yükselmiş ve hayatın uzatılması amacı gerçekleşmiştir. Bugün, değişik organların nakledilebilmesi hastaları umutlandırmıştır. Fakat nakledilebilir organ arzında sıkıntı, özellikle böbrek için, ana problem olarak durmaktadır. Nakledilebilen organ sadece bağışlardan elde edilmektedir: mevta ve canlı donör bağışları. Dünya Sağlık Örgütü (WHO) organ alım satımını yasakladıktan sonra nakli yapılabilecek organ kaynağı olarak tek kaynak gönüllü bağış kalmıştır.

Bu tez organ naklinin tarihi gelişimiyle başlamıştır. Nakil ameliyatları birçok tarihi kaynakta konu edilmiştir. İlk başarılı organ nakli 1936 da Yurii Voronoy tarafından yapılmıştır. İmmunosupresiflerin keşfinden sonra insandan insana böbrek nakli başarılı şekilde gerçekleşmeye başlamıştır. Bu başarı karaciğer, akciğer ve doku gibi başka organların nakline de imkân tanımıştır.

Nakledilebilir organ azlığı ve organ nakli ihtiyacı beraberinde etik ve moral endişeleri artırmıştır. Bu sebeple nakledilebilir organlar için dağıtım, toplama ve bağış sebebiyle yasal düzenlemelerin yapılmasını zorunlu kılmıştır. Bu tezde uygunluk için Türkiye’deki yasal durumun tarihi gelişimi ile alakalı kısa bilgi verilmiştir.

Dünyada yapılan organ nakillerinin %70 den fazlası böbrek naklidir bu sebeple çalışma böbrek nakline odaklanmıştır. Böbrek hastalığının tespiti, belirtileri, aşamaları ve nakle giden diyaliz süreçlerini anlamak için Kronik Böbrek Yetmezliğini anlamak gereklidir.

5. bölümde dünyadaki bağış sistemleri incelenmiştir. Bu sistemler merkezleri itibariyle farklılık gösterdiğinden sağladığı yararların da açıklanması gerekmektedir. Her bir sistemin kendine has perspektifi bulunmaktadır ve devletler bu perspektife göre sistemleri uygulamaktadır. Sistemler üç grupta incelenebilir: zorunlu bağış, gönüllü bağış ve parasal teşvik. Her bir sistemin mevta ve canlı donöre bakan yönü bulunmaktadır. Bir diğer sistem de bağışlanan organların dağıtımını konu almaktadır: ikili böbrek değişimi

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ve/veya NEAD Zinciri. Bu sistemler bağış miktarını artırmaktan ziyade dağıtımın etkili olmasına odaklanmıştır.

6. Bölümde böbrek dağıtım sistemleri ekonomik boyutlarıyla ele alınmıştır. Arz ve talep bileşenleri, parasal teşvikin arz ve talebe etkileriyle beraber incelenmiştir.

Parasal teşvik özellikle fakir ülkelerde organ bağışını artırmada etkili olacaktır. Organ ve nakil turizmiyle alakalı karaborsa konusu Bölüm 7 de ele alınmıştır. Dünya Sağlık Örgütü (WHO) tarafından yayınlanan raporlara göre her yıl dünyada gerçekleştirilen organ nakillerinin yaklaşık %5 ila %10 u organ kaçakçılığıyla yapılmaktadır. Bu noktada yasadışı organ kaçakçılığına iten faktörleri anlamak önemlidir. Bu faktörlerin altında yatan temel sebeplerin takip edilmesi, zorlu koşullarla baş etmeye çalışan ve acı çeken insanların organ kaçakçıları tarafından suiistimal edilmesi ve yaşamlarını değiştirmeye ikna edecek öneriyle kaçakçıların bu durumlarından avantaj sağlanmasını engellemek açısından anlamlıdır.

Yasal düzenlemeler bağış oranlarının artırılması (ve azaltılması) ve toplanan bağışların dağıtılmasında ana etkendir. Bu tez bağış oranlarının artırılması için bir öneri sunmaktadır bu sebeple yasal düzenlemelerin yapısı ve Türkiye’deki bağış ve yasal düzenlemelerin yapısı bilinmeli dir. Bu sebeple takip eden bölümde bu düzenlemeler tartışılmıştır.

8. bölümde Türkiye’deki yasal düzenlemelerle ilgili kısa bir listeleme yapılmış ve Bölüm 9 da 1990lardan günümüze nakil miktarları ve bağışlarındaki değişimleri karşılatırmıştır. Hasta seçimi ve alınmış organın dağıtımı bu bölümde incelenmiştir.

Bu tezin ana teması Türkiye’de diyaliz ve böbrek naklinin maliyet fayda analizidir. Bu konu diyalizin ve naklin maliyetlerinin hesaplanmasını gerektirmektedir. Devlet her bir diyaliz seansı için standart bir ücret ödemektedir ve bu miktar her sene enflasyona bağlı olarak revize edilmektedir. Fakat nakil maliyetleriyle ilgili gerçekçi veri elde etmek, Kişisel Bilgilerin Gizliliği Yasası gereği mümkün olmamaktadır. Bu çalışmada kullanılan veriler Atatürk Eğitim ve Araştırma Hastanesi’nden özel izinle elde edilmiştir. Bu veriler çalışmanın anahtar bileşenidir. Böbrek naklinin maliyet-fayda analizi yapıldıktan sonra Türkiye’de böbrek nakliyle diyalizin maliyetleri karşılaştırılmıştır. Buna ek olarak diğer ülkelerdeki benzer analizler taranmış ve listelenmiştir. Farklı bağış oranları, bekleme listesindeki değişim ve nakil miktarlarındaki değişime göre duyarlılık analizi yapılmıştır.

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Önerilen alternatif bağış sisteminin bir ayağını da parasal teşvik oluşturmaktadır. Parasal teşvikin miktarı ve bağış oranlarına etkisi 12. Bölümde ele alınmıştır. Bu böbreğin ticarileştirilmesi olarak ele alınmamalıdır. Gönüllü bağışta hasta, hastane ve hatta devlet (sigorta sistemi) bir çıkar elde ederken donör sadece moral rahatlama hissetmektedir ki bu da olası donörleri bağış yapmaya cesaretlendirmek için yetmemektedir. Bu noktada parasal teşvikin miktarı olası donörleri cesaretlendirmeyi sağlayacak motive eden faktör olacaktır.

Bölüm 13 alternatif bağış sistemi önerisine odaklanmaktadır. Bu öneri üç alt başlığa bölünmüştür: zorunlu bağış, devlet denetimi ve parasal teşvik. Her bir alt başlığın yararları ve literatürdeki tartışmaları bu bölümde incelenmiştir.

Her rejim ve öneriyle alakalı süregelen tartışmalar mevcuttur. Organ açığı arttıkça, özellikle son birkaç on yılda, parasal teşvikin etkisi bütün açık ve eksikliklerine rağmen geniş bir şekilde tartışılmaya başlanmıştır. Dünyada bu sistemi uygulayan ve bekleme listesini bitirmede başarılı olan tek ülke İran’dır. İran sisteminin başarısı ve eksikleri de bu bölümde ele alınmıştır.

Atatürk Araştırma Hastanesinden elde edilen verilen fazlasıyla karışık ve üzerinde çalışmaya muhtaçtır. Bu sebeple veriler teze eklenmemiştir. Gerek duyulması halinde yazarın izni karşılığında kendisinden temin edilebilir.

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