ÁGNES KRISZTINA KOVÁCS M.D. HEALTH ECONOMIC EVALUATION OF CHRONIC UROLOGIC DISEASES 1 Department of Health Economics SUPERVISORS: PROF. MÁRTA PÉNTEK PROF. LÁSZLÓ GULÁCSI COPYRIGHT ® ÁGNES KRISZTINA KOVÁCS M.D. 2 CORVINUS UNIVERSITY OF BUDAPEST DOCTORAL SCHOOL OF BUSINESS ADMINISTRATION HEALTH ECONOMIC EVALUATION OF CHRONIC UROLOGIC DISEASES PHD THESIS ÁGNES KRISZTINA KOVÁCS M.D. Budapest, 2017 3 4 TABLE OF CONTENTS LIST OF TABLES 7 LIST OF FIGURES 8 SHORT SUMMARY 9 LIST OF ABBREVIATIONS 11 1. INTRDUCTION 12 2. SHORT INTRODUCTION TO THE IMPORTANT METHODS AND TERMS USED IN THE THESIS AND TO THE DISEASES UNDER EVALUATION 19 2.1 Methods used in the thesis 19 2.1.1 Quality of life surveys 19 2.1.1.1 EQ-5D Generic health status questionnaire 19 2.1.1.2 Disease specific questionnaires 20 2.1.2 Calculation of disease burden and costs 21 2.1.3 Short description of the diseases included in the thesis 24 2.3.1.2 Bladder cancer 25 Epidemiology of bladder cancer 25 2.1.3.1 Urinary incontinence 30 Epidemiology of urinary incontinence 31 3. OBJECTIVES 38 3.1 Assessing social burden and cost of illness in benign prostatic hyperplasia 38 3.2 Cost of illness of bladder cancer in Hungary 38 3.3 Male and female urinary incontinence and the epidemiology of lower urinary tract symptoms in Hungary 39 3.4 Health economic analysis of the treatment of overactive bladder syndrome 39 4. HYPOTHESES 40 4.1 Assessing social burden and cost of illness in benign prostatic hyperplasia 40 4.2 Cost of illness of bladder cancer in Hungary 40 4.3 Male and female urinary incontinence and the epidemiology of lower urinary tract symptoms in Hungary 40 4.4 Health economic analysis of the treatment of overactive bladder syndrome 41 5. METHODS 42 5.1 Assessing social burden, cost of illness and quality of life in benign prostatic hyperplasia 42 5.1.1 Literature review 42 5.1.2 Cross-sectional questionnaire survey (2014) 43 5.2 Cost of illness of bladder cancer in Hungary 48 5.2.1 Analysis of the National Health Insurance Fund’s drug and patient flow database 48 5.3 Male and female urinary incontinence and the epidemiology of lower urinary tract symptoms in Hungary 49 5.3.1 Epidemiology and the surgical treatment practice of female urinary incontinence in Hungary 49 5 5.3.2 The prevalence of lower urinary tract symptoms in Hungarian men 50 5.4 Health economic analysis of the treatment of overactive bladder syndrome 51 6. RESULTS, DISCUSSION AND CONCLUSIONS 52 6.1 Assessing social burden, cost of illness and quality of life in benign prostatic hyperplasia 52 6.1.1 Literature review 52 6.1.1.1 Literature research 52 6.1.1.2 Costs 53 6.1.1.3 Discussion of results 55 6.1.1.4 Conclusions 57 6.1.2 Cross-sectional questionnaire survey: cost of illness and quality of life of patients diagnosed with benign prostatic hyperplasia 61 6.1.2.1 Cross-sectional questionnaire survey: cost of illness of patients diagnosed with benign prostatic hyperplasia 61 Questionnaire based cross-sectional survey; life quality of patients with benign prostatic hyperplasia 72 6.2 Quality of life and cost of illness in patients with bladder cancer in Hungary 82 6.2.1 Cost of illness in bladder cancer patients 82 6.3 Epidemiology of male and female urinary incontinence and lower urinary tract symptoms in Hungary 94 6.3.1 Surgical treatment practice of female urinary incontinence and urogenital prolapse in Hungary 94 6.3.2 The prevalence of male lower urinary tract symptoms in Hungary 103 6.4 Health economic evaluation of the treatment of overactive bladder syndrome 110 6.4.1 Results 110 7. ANSWERS GIVEN TO THE HYPOTHESES 115 7.1 Studying the costs and social burden of benign prostatic hyperplasia 115 7.2 Costs of bladder cancer in Hungary 117 7.3 Epidemiology of male and female urinary incontinence and lower urinary tract symptoms in Hungary 117 8. NEW SCIENTIFIC RESULTS IN THE DISSERTATION 119 8.1 Assessing social burden and costs of disease in patients with benign prostatic hyperplasia 119 8.2 Costs of bladder cancer in Hungary 119 8.3 Epidemiology of male and female urinary incontinence and lower urinary tract symptoms in Hungary 120 8.4 Health economic evaluation of the treatment of overactive bladder syndrome 120 9. SUMMARY 121 10. PUBLICATIONS ON WHICH THE PHD THESIS IS BASED 126 11. REFERENCES 128 12. ANNEXES 137 6 LIST OF TABLES Table 1 Costs of BPH per patient 61 Table 2 Costs of bigger patient populations or total nationwide cost 63 Table 3 The demographic and clinical characteristics of the patient population 65 Table 4 Use of health care resources in the past 12 months 67 Table 5 Annual per-patient costs of BPH (€, 2014) 69 Table 6 Demographic characteristics of patients (n=246) 77 Table 7 Clinical characteristics of patients 78 Table 8 The general quality of life of BPH patients measured with EQ-5D in subgroups according to symptoms and severity of the disease 80 Table 9 Correlation between continuous variables 81 Table 10 Sales of medicinal products with special social security reimbursement to be prescribed in bladder cancer indication, number of packages sold, 2008 - 2014 89 Table 11 Social security reimbursement paid between 2008 and 2014, HUF 90 Table 12 Product turnover of Mitomycin-C Kyowa, powder for solution for injection between 2008 and 2012 92 Table 13 The turnover of medications for low or medium-risk urinary bladder cancer for intravesical instillation with 100% social security funding in 2014 94 Table 14 Turnover of medications with 100% social security funding which can be used for intravesical instillation in case of high-risk urinary bladder tumor and in situ carcinoma (BNO C679), 2014 95 Table 15 The age distribution of participants 107 Table 16 Questions of the I-PSS survey relating to incontinence symptoms 109 Table 17 Questions from the I-PSS survey relating to emptying complaints 109 Table 18 Number and age of the international participants 111 Table 19 Results of the cost effectiveness analysis, costs of one continent patient 114 7 LIST OF FIGURES Figure1 Life expectancy at birth (2014) 12 Figure2 Life years gained (1960-2009) 13 Figure 3 Hungarian population by sex and age group, as of 1 January 2017 (thousands persons) (N= 9 690 388 persons) 14 Figure 4 (Expected) number of the Hungarian population by sex and age group, as of 1 January 2030 (thousands persons) (N= 9,690,388 persons) 15 Figure 5 Number of new patients reported with diagnosis of benign neoplasm of bladder (ICD D30.3) between 2001 and 2011 27 Figure 6 Number of new patients reported with diagnosis of malignant neoplasm of bladder (ICD D30.3) between 2001 and 2011 27 Figure7 New cases of malignant bladder cancer by age groups in Hungary in 2011 29 Figure 8 Per-patient costs by cost category in the I-PSS severity groups 68 Figure 9 Comparison of BPH patients and age- and sex-matched general population in the 5 dimensions of the EQ-5D questionnaire 78 Figure 10 Comparison of BPH patients and the age- and sex-matched general population in the EQ-5D index 79 Figure 11 Changes of product turnover and sold active agent quantity of epirubicin and mitomycin containing products between 2008 and 2014 88 Figure 12. Did you ever exprience any urine leakage? 94 Figure 13. How much are you irritated by involuntary urine leakage? - age distribution 95 Figure 14. Distribution of incontinence surgeries on gynecology and urinary wards 98 Figure 15. How often does it happen that you cannot hold your urine? 99 Figure 16. How much are you irritated by involuntary urine leakage? 99 Figure 17. In case of urinary urges, do you have to go to the toilet immediately or can you wait? 100 Figure 18. Distribution of symptoms in each age group according to I-PSS categories 104 Figure 19. Distribution of patients showing “rather voiding” and “rather storage” symptoms by age groups based on the I-PSS survey. 106 Figure 20. Adoption curve 113 8 SHORT SUMMARY In my thesis I provide analysis of the health economic aspects of chronic prostatic diseases including benign prostatic hyperplasia, bladder cancer, female and male urinary incontinence, lower urinary tract symptoms and overactive bladder syndrome. Due to the ageing of the population the prevalence and social burden of these diseases increase substantially. These diseases already at present have major cost impacts and the related costs are expected to rapidly increase further in the near future. The disease incidence within the specified age groups appears to be fairly constant, however due to the increasing life expectancy of the population and to the more and more effective therapeutic agents, the total number of patients rise significantly. The costs rise constantly since these chronic diseases are long-lasting and require ongoing medical care. Due to the constantly increasing patient number and social burden these issues receive special attention in more and more developed countries. Some countries develop “ageing strategies” and health economic research of ageing is in the mainstream of health economic research. Substantial data are required in order to make adequate health policy decisions and to find sustainable finance solutions. Little is known about the epidemiology and social burden of chronic urologic diseases in Hungary which makes adequate decision-making in health policy and finance remarkably difficult. In order to come to know the social burden we need to be aware of the epidemiology of these diseases including the number of new cases (incidence), the total patient number (prevalence), the number of patients in the subgroups important from disease severity aspects (since the costs are related to disease severity), the direct and indirect costs associated with the disease and the quality of life implications of the disease. 9 These pieces of information are necessary in order to assess the real social importance of the diseases and to calculate the budget impact and cost-effectiveness of the newer and newer and more and more expensive therapies which is an obligation of the social security system and is also essential to develop a sustainable health care finance system. The research published in the thesis includes the health economic evaluation of several chronic urologic diseases since we need to compare these results. In order to make ranking possible for health policy and financing purposes it is necessary to know the number of patients with the diseases concerned, the direct and indirect costs and the implications on quality of life and work i.e. the social burden. The aims and the hypotheses set for the specific diseases under investigation differed with consideration to the characteristics of the field and the available Hungarian and international literature, so did the methodology applied differ as well. The research results published in the thesis previously were not available either in Hungary or in the wider region; furthermore we have successfully found and published several results for the first time in the literature. The research results fill a knowledge gap and can be of use for promoting decision making in health policy and finance. 10