University of Groningen Health economics of tick-borne diseases Smit, Renata IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2016 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Smit, R. (2016). Health economics of tick-borne diseases [Groningen]: Rijksuniversiteit Groningen Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 11-02-2018 Health Economics of Tick-Borne Diseases Renata Šmit 1 This work was performed within the Research Institute SHARE (Science in Healthy Ageing and healthcaRE) of the University Medical Center Groningen, Faculty of Medical Science, University of Groningen. The printing of this thesis was financially supported by the University of Groningen, the Research Institute SHARE of the Faculty of Medical Sciences and the Groningen Graduate School of Science. Author: Renata Šmit Cover: Image of tick by CanStockPhoto Printed by GrafiMedia ISBN: 978-90-367-9019-2 (printed version) ISBN: 978-90-367-9018-5 (electronic version) © Renata Šmit, 2016. All rights reserved. No part of this thesis may be reproduced or transmitted in any form or by any means without written permission of the author. The copyright of previously published chapters of this thesis remains with the publisher or journal. 2 Health Economics of Tick -Borne Diseases Proefschrift ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen op gezag van de rector magnificus prof. dr. E. Sterken en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op vrijdag 18 november 2016 om 12.45 uur door Renata Šmit geboren op 11 juli 1971 te Ljubljana, Slovenië 3 Promotores Prof. M.J. Postma Prof. K. Poelstra Beoordelingscommissie Prof. H.W. Frijlink Prof. A.W. Friedrich Prof. E. McIntosh 4 To my Mom and Dad – for your continuous support and love 5 6 TABLE OF CONTENTS Chapter 1 Introduction 9 Chapter 2 Vaccines for tick -borne diseases and cost -effectiveness of 25 vaccination: a public health challenge to reduce the diseases’ burden Chapter 3 Review of tick -borne encephalitis and vaccines: clinical 33 and economical aspects Chapter 4 Lyme borreliosis: reviewing potential vaccines, clinical 61 aspects and health economics Chapter 5 The burden of tick -borne encephalitis in disability - 93 adjusted life years (DALYs) for Slovenia Chapter 6 Cost -effectiveness of tick -borne encephalitis vaccination 121 in Slovenian adults Annex 6.1 Some details on Cost -effectiveness of tick -borne 141 encephalitis vaccination in Slovenian adults Annex 6.2 Further details on Cost -effectiveness of tick -borne 145 encephalitis vaccination in Slovenian adults Chapter 7 Discussion and Conclusions 153 Summary 165 Samenvatting 167 Bibliography 169 Acknowledgements 170 Research Institute for Health Research (SHARE ) 172 Curriculum Vitae 175 7 8 CHAPTER 1 Introduction 9 10 Introduction Introduction Vaccination is one of the most health and cost effective public interventions with long-term benefits. Vaccination can protect individuals of all age groups against potentially serious infectious diseases and it can save many human lives [1]. Vaccination can be beneficial for children and adolescents in terms of growing into healthy, productive adults that can fully contribute to the economic progress of a society. Vaccination of older adults can be beneficial in terms of having a healthier and independent life. Healthy older adults can be an active family member and they can contribute to the society. Therefore, promoting vaccination for all ages and healthy ageing throughout whole life can contribute to the health of the population as a whole [2,3]. Decision-making when considering inclusion, substitution or exclusion of specific vaccine in the national vaccination programme is a demanding, time consuming and complex process [4,5]. Decision makers need information on disease epidemiology and disease burden, vaccine safety and quality and efficacy/effectiveness, duration of immunity, herd immunity, ethical and humanitarian viewpoint of vaccine, logistics and availability, vaccine licensure status, equity and preference and acceptability, and comparison with other intervention and experience of other countries when deciding on vaccination policy [6,7]. Next, health economics and financial evaluations are playing a growing role in the final decision on vaccination policy and allocation of public health resources. A basis for a decision- making can be served by making a comparison of two or more vaccines/vaccination programmes in terms of costs and health benefits. The main types of this kind of economic evaluation are cost-effectiveness analysis (CEA) and cost-benefit analysis (CBA) [6,7,8]. CEA is the most often used in decision-making process on vaccination, and its importance is only increasing. In CEA, the costs are compared to the health outcomes of at least two vaccines. Health outcomes are expressed in natural units such as cases avoided or number of life years saved. CEA results are presented as an incremental cost-effectiveness ratio (ICER). The ICER is calculated as follows: *./ *! $)/ -1 )/$*) ͯ *./ *! $)/ -1 )/$*) ̓̽̿͌ = (1) # '/# *0/*( *! $)/ -1 )/$*) ͯ # '/# *0/*( *! $)/ -1 )/$*) 11 Chapter 1 $)- ( )/' *./. ̓̽̿͌ = (2) $)- ( )/' # '/# *0/*( . Where: • Intervention A = vaccination. • Intervention B = comparator. When intervention A is a new vaccine, then its comparator is usually “no vaccination.” • Costs are expressed in a monetary unit. • Health outcomes are expressed in natural units (number of cases prevented or number of life years or number of deaths prevented). The ICER is shown as cost per health outcome, expressed in natural units. CEA is used to find the most cost-effective vaccination strategy between different vaccines. It is also used for resource allocation and reimbursement decision making of vaccination [4,6,7,8]. A special type of CEA is cost-utility analysis (CUA) in which health outcomes are measured in terms of quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs). The ICER (cost-utility ratio) is calculated as follows: $)- ( )/' *./. ) / *./. ̓̽̿͌ = = (3) $)- ( )/' # '/# *0/*( . . *- . In CUA, the ICER is shown as cost per QALYs gained or cost per DALYs averted. QALYs are defined as a measure of the value of patients’ health states. QALYs are one measure that combine both the quantity and the quality of patients’ life. One QALY means one year living in perfect health. QALYs are calculated as follows: ̻͓͋͆ͧ = ͩͨͨͭ͝͠͝ ̻ ͬ ͙͕ͭͦͧ ͙ͧͤͨ͢ ͢͝ ℎ͕ͨ͠ℎ ͕͙ͧͨͨ ̻ + ͩͨͨͭ͝͠͝ ͬ ͙͕ͭͦͧ ͙ͧͤͨ͢ ͢͝ ℎ͕ͨ͠ℎ ͕͙ͧͨͨ ̼ (4) Where: • Utility or weights = relative value between 0 (death) and 1 (perfect health), expressed as preference from the patient’s perspective for a specific health state. 12 Introduction QALYs can be used to estimate the disease burden. QALYs are one of criteria that can be used for making a decision and for allocation of finite public health resources [4,6,7,8,9]. DALYs are one measure that combines both premature death (YLLs) and disability due to morbidity (YLDs). DALYs are calculated as follows: DALYs = YLLs + YLDs (5) Where: • YLLs = the number of life years lost due to premature death. • YLDs = the number of life years lost due to disability, weighted with a factor between 0 (perfect health) and 1 (death) that reflects the severity of disability. The DALYs methodology, which was first introduced by Murray and co-workers in the Global Burden of Disease project, is usually used to estimate the burden of disease. The World Health Organization (WHO) defines DALYs as the lost years of healthy life. The WHO recommends calculation the burden of the disease expressed in DALYs [6,10]. DALYs can be used to compare relative burdens among different diseases and among different populations [11] and they can be used to prioritize of limited public health resources [12]. Therefore, DALYs can be a useful tool in the decision-making process. In cost-benefit analysis (CBA), both costs and health benefits are measured in monetary units. In CBA, net benefit is calculated by deducting value of costs from value of health benefits. If net benefit is positive then the vaccination programme is recognized as an optimal investment. Benefit-cost ratio is calculated by dividing health benefits by costs. If benefit-cost ratio is higher than 1 then a vaccination programme is recognized an optimal investment. Health benefits are difficult to express in monetary units, therefore CBA is not often used for the economic evaluation of vaccines/vaccination programme [6,7,8] In contrast with CEA, CUA and CBA, the cost analysis (CA) compares only the costs of a vaccines/vaccination programme with the costs of its comparator(s). The cost minimization analysis