Economic studies of chronic kidney disease

ECONOMIC STUDIES OF CHRONIC KIDNEY DISEASE A thesis submitted for the Degree of Doctor of Philosophy (Ph.D.) to the Faculty of Medicine, Health and Life Sciences School of Medicine, Dentistry and Biomedical Sciences Queen’s University Belfast by Nga TQ Nguyen, BPharm Supervisors: Professor Ciaran O’Neill Professor Michael Donnelly October 2020 DECLARATION I declare that: The thesis is not one for which a degree has been or will be conferred by any other university or institution; The thesis is not one for which a degree has already been conferred by this University; The work for the thesis is my own work and that, where material submitted by me for another degree or work undertaken by me as part of a research group has been incorporated into the thesis, the extent of the work thus incorporated has been clearly indicated The composition of the thesis is my own work i ABSTRACT Approximately 9% of the global population has chronic kidney disease (CKD) Patients with end-stage renal disease (ESRD), the most advanced form of CKD, comprise 0.15% of the global population but consume 2-4% healthcare budgets While the impact of CKD and ESRD are experienced most immediately by people with these diseases, the impact extends beyond them to include the healthcare system and wider society in terms of, for example, the costs and legal framework that are required to ensure good governance around organ donation These impacts vary between countries, depending, inter alia, on access to resources and societal attitudes It is important to investigate and compare impacts across contexts in order to improve our understanding This PhD examined distinct aspects of these impacts across contexts using a variety of analytic approaches Chapter examined the relationship between health-related quality of life (HRQoL) and CKD severity, and the consequent economic impact due to reduced HRQoL among a representative sample of community dwelling adults in the United Kingdom The evident decline in HRQoL among people even with milder stages of CKD underscored the importance of primary prevention, early diagnosis and secondary prevention in reducing the impact of CKD As ESRD is expensive and access to renal replacement therapies (RRTs) is limited in many circumstances, there is considerable potential for disparities to occur in relation to the management of ESRD Chapter examined disparities among ESRD inpatients taking into account changes in the policy context in the United States of America Significant racial disparities regarding recorded anaemia, a modifiable and common complication of CKD, were observed Not only did Native Americans as a group experience the worst outcomes but their relative position declined after changes to policy Chapter underlined unintended consequences of policy changes that may have been preventable Complementing global efforts to address organ shortage, Chapter examined attitudes (conceptualised in terms of passive support) and behaviours (conceptualised in terms of active support) related to tissue donation after death among citizens from 27 European countries Here, a mismatch and unobserved heterogeneity between passive ii and active support for tissue donation, was observed which underscored the importance of examining both types of support together in order to attain a more complete understanding about attitudes and how, potentially, they shape behaviours Chapter found the potential of incorporating both selfless and selfish motivations to translate latent passive into active support for donation Finally, despite the evident medical benefits of living donor kidney transplantation (LDKT), there is limited information about the economic impact of LDKT in the UK The final chapter reviewed the evolution of the LDKT program in Northern Ireland, which currently leads the world in terms of living donor rate, and considered the implications of the program’s evolution for future cost-effectiveness studies Using the linked data provided by the Belfast Health and Social Care (HSC) Trust and the Northern Ireland HSC Business Service Organization, Chapter demonstrated the superiority of LDKT over deceased donor kidney transplantations in terms of survival outcomes Furthermore, it demonstrated how this superiority persisted, despite the increasing complexity of case mix over time The chapter concluded by presenting a road map for a subsequent full economic evaluation of the LDKT program In summary, the PhD thesis identified a number of economic aspects of CKD and ESRD including economic impact, equity in care, potential approaches to address the organ shortage crisis and the implication of program evolution for costeffectiveness analyses iii ACKNOWLEDGEMENT First and foremost, I would like to express my greatest gratitude to my two supervisors Prof Ciaran O’Neill and Prof Michael Donnelly You are the best supervisors I could ever wish for, thank you for your invaluable guidance and immeasurable support, your encouragement and patience, and your positive energy that have fulfilled my PhD journey What you have taught me sets a steady foundation for my future career I am also grateful to the late Prof Liam Murray who opened the door for me to Queen’s and gave me the great support since my first step in this journey To Ms Heather Taylor and the CPH Admin team, thank you for your continuous support My thesis as well as the other research I have been involved in have been considerably improved thanks to many of the collaborators I would like to send especial thanks to Prof Peter Maxwell, Dr Aisling Courtney, Dr Michael Quinn, and Dr Grainne Crealey for your expertise and advice I also wish to thank everyone in Centre for Public Health, the Cancer Epidemiology and Health Services Research Group, and the Honest Broker Service team who provided me with support and advice throughout my study To my friends at Centre for Public Health, NUI Galway, CEM, and the Vietnamese community at Belfast, thank you for making my everyday enjoyable and making Belfast my second home Special thanks to Jinnan, Haydee, KimTu, Ngan, Anna, Luke, Dan, Danielle, Ethna, Leonie, and Euan To my friends and colleagues in Vietnam, thank you for keeping me posted with continuous changes in my home country To my parents, my parents-in-law, and my three handsome brothers, thank you for your unconditional and infinite love which have shaped me the way I am today To my Mom, thank you for inspiring me to become a strong and independent woman I am also grateful for my funding VIED and my University in Vietnam for giving me the opportunity to pursue my PhD at Queen’s To the examiners, thank you for giving me such a friendly and helpful viva, for your comments and advice that improved the quality of my thesis Finally, to my husband, your incredible support, inspiration, patience, and your love have lifted me up and sparked joy to my life I am so lucky to have you accompany me in this challenging but colourful journey Thank you for everything! iv TABLE OF CONTENTS DECLARATION i ABSTRACT ii ACKNOWLEDGEMENT iv TABLE OF CONTENTS v LIST OF TABLES xi LIST OF FIGURES xii LIST OF APPENDICES xv DISSEMINATION OF RESULTS xvi LIST OF ABBREVIATION xvii Chapter INTRODUCTION 1.1 CHRONIC KIDNEY DISEASE 1.1.1 Kidney function 1.1.2 Chronic kidney disease definition and classification 1.1.3 Epidemiology 1.1.4 CKD management 15 1.2 END-STAGE RENAL DISEASE 20 1.2.1 End-stage renal disease definition 20 1.2.2 Epidemiology 21 1.2.3 ESRD management 28 1.3 ECONOMIC IMPACT OF CKD AND ESRD 38 1.3.1 Mortality 39 1.3.2 Morbidity 41 1.3.3 Healthcare cost of CKD and ESRD 43 1.4 AIM AND OBJECTIVES OF THIS THESIS 46 1.4.1 Aim of this thesis 46 v 1.4.2 Objectives of this thesis 46 1.4.3 Structure of this thesis 48 Chapter HEALTH-RELATED QUALITY OF LIFE AMONG PATIENTS WITH CHRONIC KIDNEY DISEASE AND THE ASSOCIATED ECONOMIC IMPACT IN THE UNITED KINGDOM 49 2.1 INTRODUCTION 49 2.1.1 Chronic kidney disease 49 2.1.2 Health-related quality of life 50 2.1.3 Aim of the study 52 2.2 METHODS 52 2.2.1 Data source 52 2.2.2 Statistical analysis 53 2.2.3 Sensitivity analysis 55 2.2.4 Projecting economic burden of CKD 56 2.3 RESULTS 57 2.3.1 Descriptive statistic 57 2.3.2 Base case analysis 60 2.3.3 Sensitivity analysis 61 2.3.4 The relationships between CKD status and the specific EQ-5D domains of health 65 2.3.5 The burden of chronic kidney disease and projections among those with diabetes to 2025 66 2.4 DISCUSSION 68 2.4.1 Strengths 70 2.4.2 Limitations 71 2.4.3 Implication for future study 72 2.5 CONCLUSION 73 vi Chapter INPATIENT CARE FOR END-STAGE RENAL DISEASE PATIENTS IN THE UNITED STATES 74 3.1 INTRODUCTION 74 3.1.1 Anaemia and policy changes related to anaemia treatment 76 3.1.2 Depression 78 3.1.3 Mortality 79 3.1.4 Hospital incurred costs 80 3.1.5 Aim of the study 81 3.2 METHODOLOGY 82 3.2.1 Data source and study population 82 3.2.2 Study outcomes 83 3.2.3 Study variables 84 3.2.4 Statistical analyses 85 3.2.5 Sensitivity analyses 91 3.3 RESULTS 92 3.3.1 Descriptive statistics 92 3.3.2 Racial/ethnic disparities in anaemia complication 98 3.3.3 Depression 102 3.3.4 Inpatient mortality 104 3.1.2 Discharge destination 107 3.3.5 Length of stay in the hospital 109 3.3.6 Hospital incurred costs 110 3.3.7 Sensitivity analyses 112 3.4 DISCUSSION 113 3.4.1 Changes in the number of hospitalizations with ESRD over time 113 3.4.2 Racial/ethnic disparities 114 3.4.3 Depression among inpatients with ESRD 119 vii 3.4.4 Inpatient mortality 121 3.4.5 Costs and length of stay in the hospital 122 3.4.6 Strengths 124 3.4.7 Limitations 124 3.5 CONCLUSION 126 Chapter UNDERSTANDING SUPPORT FOR TISSUE DONATION ACROSS 27 EUROPEAN COUNTRIES 128 4.1 INTRODUCTION 128 4.1.1 Organ and tissue donation 128 4.1.2 Donation legislation 130 4.1.3 Motivations and reservations 131 4.1.4 Aim of the study 133 4.2 METHODS 134 4.2.1 Data source 134 4.2.2 Study variables 134 4.2.3 Statistical analyses 137 4.3 RESULTS 140 4.3.1 Characteristics of the study cohort 140 4.3.2 The unobserved heterogeneity in the correlation between passive and active support for tissue donation 144 4.3.3 The association of legal context and support for tissue donation 145 4.3.4 The association of motivational contexts and support for tissue donation 147 4.3.5 Age generation and support for tissue donation 149 4.4 DISCUSSION 150 4.4.1 Limitations 156 4.5 CONCLUSIONS 157 viii Chapter PERSPECTIVES ON LIVING DONOR KIDNEY TRANSPLANTATION IN NORTHERN IRELAND: IMPLICATIONS FOR COST-EFFECTIVENESS STUDIES 159 5.1 INTRODUCTION TO KIDNEY TRANSPLANTATION 160 5.1.1 Renal replacement therapy 160 5.1.2 Living donor kidney transplantation 162 5.1.3 Transplant activity in the UK 171 5.2 THE EVOLUTION OF THE LIVING DONOR TRANSPLANTATION PROGRAM IN NORTHERN IRELAND AND IMPLICATIONS FOR COSTEFFECTIVENESS ANALYSES 174 5.2.1 Kidney transplant activity in Northern Ireland 174 5.2.2 The evolution of living donor kidney transplant program in Northern Ireland since 2010 176 5.2.3 A study of the transplant population in Northern Ireland from 2010 to 2017 177 5.2.4 Implications for cost-effectiveness analyses 187 5.3 EQUALITY IN LIVING DONOR KIDNEY TRANSPLANTATION 192 5.3.1 Socio-economic disparities 193 5.3.2 Ethical consideration 198 5.4 POTENTIAL FUTURE RESEARCH 199 5.5 CONCLUSION 202 Chapter DISCUSSION AND CONCLUSION 203 6.1 SUMMARY OF MAIN FINDINGS 203 6.1.1 The impact of early stages CKD 203 6.1.2 The potential unintended consequences of policy 205 6.1.3 Kidney transplantation programs 207 6.2 POLICY IMPLICATIONS 210 6.2.1 CKD and ESRD prevention 210 ix ... ABSTRACT Approximately 9% of the global population has chronic kidney disease (CKD) Patients with end-stage renal disease (ESRD), the most advanced form of CKD, comprise 0.15% of the global population... xii LIST OF APPENDICES xv DISSEMINATION OF RESULTS xvi LIST OF ABBREVIATION xvii Chapter INTRODUCTION 1.1 CHRONIC KIDNEY DISEASE 1.1.1 Kidney. .. Acute kidney disease Average marginal effect Analysis of variance Adjusted Odds ratio Bayesian information criterion Deyo-Charlson Comorbidity Index Confidence interval Chronic Kidney Disease Chronic