Pharmacoeconomic methods for cost effectiveness

Timo Purmonen Pharmacoeconomic Methods for Estimating Cost-effectiveness and Budget Impact of Cancer Treatments in Finland Publications of the University of Eastern Finland Dissertations in Health Sciences TIMO PURMONEN Pharmacoeconomic methods for estimating cost-effectiveness and budget impact of cancer treatments in Finland To be presented by permission of the Faculty of Health Sciences, University of Eastern Finland for public examination in Mediteknia Auditorium, Kuopio, on Saturday, October 27th 2012, at 13:00 Publications of the University of Eastern Finland Dissertations in Health Sciences 124 School of Pharmacy Faculty of Health Sciences University of Eastern Finland Kuopio 2012 Juvenes Print - Suomen Yliopistopaino Oy Tampere, 2012 Series Editors: Professor Veli-Matti Kosma, M.D., Ph.D Institute of Clinical Medicine, Pathology Faculty of Health Sciences Professor Hannele Turunen, Ph.D Department of Nursing Science Faculty of Health Sciences Professor Olli Gröhn, Ph.D A.I Virtanen Institute for Molecular Sciences Faculty of Health Sciences Distributor: University of Eastern Finland Kuopio Campus Library P.O.Box 1627 FI-70211 Kuopio, Finland http://www.uef.fi/kirjasto ISBN (print): 978-952-61-0858-2 ISBN (pdf): 978-952-61-0859-9 ISSN (print): 1798-5706 ISSN (pdf): 1798-5714 ISSN-L: 1798-5706 III Author’s address: School of Pharmacy University of Eastern Finland KUOPIO FINLAND Supervisors: Associate Professor Janne Martikainen, Ph.D School of Pharmacy University of Eastern Finland KUOPIO FINLAND Professor Hannes Enlund, Ph.D Finnish Medicines Agency KUOPIO FINLAND Reviewers: Professor Marja Blom, Ph.D Faculty of Pharmacy University of Helsinki HELSINKI FINLAND Adjunct Professor Risto P Roine, M.D., Ph.D Hospital district of Helsinki and Uusimaa HELSINKI FINLAND Opponent: Adjunct Professor Juha Laine, Ph.D Pfizer Oy HELSINKI FINLAND IV V Purmonen, Timo Pharmacoeconomic methods for estimating cost-effectiveness and budget impact of cancer treatments in Finland University of Eastern Finland, Faculty of Health Sciences, 2012 Publications of the University of Eastern Finland Dissertations in Health Sciences 124 2012 84 p ISBN (print): 978-952-61-0858-2 ISBN (pdf): 978-952-61-0859-9 ISSN (print): 1798-5706 ISSN (pdf): 1798-5714 ISSN-L: 1798-5706 ABSTRACT Economic evaluations are being used increasingly often in attempts to meet the challenges of optimally allocating scarce health care resources The cost-effectiveness of cancer treatments has been assessed widely perhaps because there is a global interest about the economic issues related to cancer Cancer is one of the leading causes of morbidity and mortality worldwide, and thus, is a major challenge to health care funding The burden of cancer is likely to increase due to ageing of the population, intensive care with targeted drugs, and increasing treatment costs Thus, cancer consumes a large and potentially increasing proportion of the total health care budget The general aim of this thesis was to study pharmacoeconomic methods and to apply them to evaluate the cost-effectiveness and budget impact of cancer treatments in Finland In most cases, new treatments are more effective but also more expensive compared to their predecessors The thesis consists of studies into sunitinib in the treatment of metastatic renal cell carcinoma (mRCC), and trastuzumab in the treatment of HER2-positive early breast cancer The studies include various elements of economic evaluations, including cost-effectiveness analyses, budget impact analyses, value of information analyses, and burden of illness estimates The utilized methods were chosen individually in each of the studies The results of this thesis revealed that renal cell carcinoma imposes a considerable economic burden on society, and leads to premature deaths and productivity losses Sunitinib was found to be costeffective as a second line treatment compared to the current treatment practice at the time of the study (best supportive care), in Finland The conducted literature review revealed that sunitinib could be considered as a cost-effective treatment option in the treatment of mRCC, globally Analyses of short-course trastuzumab demonstrated a good cost-effectiveness profile compared to treatment without trastuzumab, in HER2-positive early breast cancer The value of information analysis illustrated that most of the uncertainty in the results was related to effectiveness parameters Furthermore, the budget impact analysis indicated that treatment length has a major effect on the budget impact of trastuzumab Pharmacoeconomic methods represent a useful tool to support decision making related to the introduction of new cancer treatments These studies revealed that the utilized cancer model was suitable for modeling the natural disease progression with respect to mRCC and breast cancer Although the results, based on modeling, are surrounded by uncertainty, this may be quantified to reduce decision uncertainty A probabilistic approach was applied to cost-effectiveness analyses and budget impact analysis This approach can achieve a better recognition of uncertainty and it enhances the methodology currently used in budget impact analyses National Library of Medicine Classification: QV 269, QV 736, QZ 267 Medical Subject Headings: Costs and Cost Analysis; Cost of Illness; Economics, Pharmaceutical; Budgets; Neoplasms/drug therapy; Antineoplastic Agents; Disease Progression; Models, Statistical; Finland VI VII Purmonen, Timo Lääketaloustieteelliset menetelmät syöpälääkkeiden kustannusvaikuttavuuden ja budjettivaikutuksen arvioinnissa Itä-Suomen yliopisto, Terveystieteiden tiedekunta, 2012 Publications of the University of Eastern Finland Dissertations in Health Sciences 124 2012 84 s ISBN (print): 978-952-61-0858-2 ISBN (pdf): 978-952-61-0859-9 ISSN (print): 1798-5706 ISSN (pdf): 1798-5714 ISSN-L: 1798-5706 TIIVISTELMÄ Lääkehoitojen taloudellisia arviointeja hyödynnetään terveydenhuollon rajallisten resurssien kohdentamispäätöksiä tehtäessä yhä useammin Syöpäsairaudet ovat maailmanlaajuisesti yksi merkittävimmistä kuolleisuutta ja sairastavuutta aiheuttavista sairauksista Väestön ikääntymisen, kehittyvien ja entistä kalliimpien hoitomuotojen myötä syöpä aiheuttaa huomattavan taakan yhteiskunnalle Tulevaisuudessa syövän odotetaan vievän yhä suuremman osan terveydenhuoltoon kohdennetuista resursseista, minkä vuoksi mielenkiinto syövän hoidossa käytettävien hoitomenetelmien taloudelliseen arviointiin on lisääntynyt kustannusvaikuttavimpien hoitomenetelmien tunnistamiseksi Tämän tutkimuksen tavoitteena oli kehittää lääkehoitojen taloudellisessa arvioinnissa käytettäviä menetelmiä sekä soveltaa niitä syöpälääkkeiden kustannusvaikuttavuuden ja budjettivaikutuksen arviointiin Suomen terveydenhuollon olosuhteissa Tutkimus koostuu osatutkimuksista, joissa arvioidaan kahta lääkehoitoa (sunitinibia metastasoituneen munuaissyövän hoidossa ja trastutsumabia aikaisen vaiheen HER2-positiivisen rintasyövän hoidossa) lääketaloudellisesta näkökulmasta Osatutkimuksissa on hyödynnetty useita erilaisia taloudellisen arvioinnin menetelmiä, kuten kustannusvaikuttavuusanalyyseja, budjettivaikutusanalyyseja sekä taudin taakkaa ja lisätutkimusnäytön arvoa kuvaavia analyyseja Menetelmät eri osatutkimuksissa on valittu kyseisen tutkimuksen näkökulman ja tavoitteen mukaisesti Tutkimus osoitti, että munuaissyöpä aiheuttaa huomattavan taloudellisen taakan yhteiskunnalle, sekä johtaa ennenaikaisiin kuolemiin ja tuotannonmenetyksiin Sunitinibi-hoidon osoitettiin olevan kustannusvaikuttava toisen linjan hoitovaihtoehto verrattuna vallitsevaan hoitokäytäntöön Suomessa Lisäksi kansainvälisiin tutkimuksiin pohjautuvan kirjallisuuskatsauksen perusteella havaittiin, että sunitinibia voidaan pitää potentiaalisesti kustannusvaikuttavana hoitovaihtoehtona metastasoituneen munuaissyövän hoidossa myös maailmanlaajuisesti Lyhytkestoisen trastutsumabi-hoidon kustannukset ovat toteutetun arvioinnin perusteella kohtuulliset verrattuna sillä saavutettuihin hyötyihin aikaisen vaiheen HER2-positiivisen rintasyövän hoidossa Hoidon keston havaittiin olevan merkittävä trastutsumabin budjettivaikutukseen vaikuttava tekijä sairaanhoitopiiritasolla Suurin kustannusvaikuttavuusanalyysin tuloksiin vaikuttava yksittäinen epävarmuuden lähde liittyi trastutsumabi-hoidon tehoa kuvaaviin parametreihin Lääketaloustieteellisiä menetelmiä voidaan hyödyntää uusien syöpälääkkeiden käyttöönottopäätöksiä tehtäessä Tutkimus osoitti, että käytetty päätösanalyyttinen mallinnus soveltuu metastasoituneen munuaissyövän ja rintasyövän etenemisen kuvaamiseen Mallinnukset ovat yksinkertaistuksia todellisuudesta ja lisäksi käytettäviin parametreihin liittyy aina epävarmuutta Päätöksentekoon liittyvää epävarmuutta voidaan kuitenkin vähentää kuvaamalla parametriepävarmuuden määrää esimerkiksi tutkimuksessa käytettyjen probabilististen herkkyysanalyysien avulla Lääketaloustieteelliset 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Expert Rev Pharmacoeconomics Outcomes Res 8:433–442, 2008 Appendix Appendix A proposal for national guidelines for budget impact analysis The following proposal is based on ISPOR guidance (Mauskopf et al 2007), and national guidelines from Poland and Canada (Orlewska and Mierzejewski 2004, Marshall et al 2008), which have been synthesized according to the author’s own views considering the observed inconsistencies in previously published studies (Orlewska and Gulácsi 2009) The proposal is aimed to be a starting point for discussion about the need and content of national guidelines The purpose is to enable uniformity and comparability of budget impact analyses both nationally and internationally This proposal will also propose what could be the minimum requirement to be considered in estimating the budget impact of pharmaceuticals in Finland General structure The reporting of the methods, results, and assumptions used, should be transparent, and the analytical method should be properly presented Definition of study perspective Defining the study perspective is possibly the most important factor in a budget impact analysis This will affect all the subsequent decisions Budget impact analyses should most preferably be performed from the payer’s perspective (e.g hospital, hospital district, municipality, Social Insurance Institute) However, a societal perspective may also be utilized depending on the aim of the study Definition of treatment comparators In budget impact analysis, the introduced treatment is always compared to some other treatment It is not sufficient to calculate the cost of the new treatment, since the introduction of the treatment will have consequences on the current treatment practice Thus, a calculation of the cost of “drug A”, cannot be considered as a budget impact analysis Budget impact analysis is rather a comparison of two alternative treatment mixes – the treatment mix without new treatment and the treatment mix including the new treatment For this reason the current care has to be defined, as this forms the basis on which the changes happen, and it also acts as the comparator in the indication of interest The treatment of interest is the new introduced treatment, along with the changes it is expected to evoke in the current treatment practice over time The expected market penetration of the new product should be included as illustrations of future treatment practice Definition of target population All decisions related to target population should be made in accordance with the study perspective The target population is defined by the aim and perspective of the study, but in general it should be those patients who potentially may benefit from the treatment The target population should include all potential patients who are eligible to receive the new treatment, during the time period of the performed analysis Subgroup analyses may be performed when sufficient data is available Nevertheless, the potential consequences of an adoption decision should always be presented at a level of the entire population of interest The target population may be based on incidence, prevalence, or the combination of these depending on the treatment and disease characteristics and the study aim Hypothetical population sizes should be avoided Time horizon The time horizon should be relevant to the budget holder, for whom the analysis is performed A suitable time horizon could be years or less With a longer time perspective, the uncertainty increases substantially Selection of data sources Official data from national registers and statistics should be emphasized in the selection of data sources Data should be country-specific, identifiable and clearly stated Local registers from the target organization, published peer-reviewed literature, and clinical trials are preferred over unscientific data Protocol-driven resource use should be excluded if data from clinical trials are used Expert opinion as well as data from e.g manufacturer’s market predictions may have to be utilized due to the predictive nature of these analyses Irrespective of the utilized data source, all data should be consistent with the study perspective Use of modeling A model-based approach may be required in estimations performed over time The design of the model may vary among studies, as it should be constructed according to the needs of each individual study In principle, the budget impact model should be an open cohort model, but the use of closed cohort models cannot be ruled out Resource use and unit costs Resource use should ideally be based on the actual resource use observed in the target organization The unit costs from the target organization should be used if possible Alternatively, in Finland, Finnish health care unit costs, which depict the average costs in the whole country, may be used (Hujanen et al 2008) Aggregate level costs may be used if necessary Discounting Discounting is not recommended Budget impact analysis deals with financial streams over time, and thus it is not necessary to use discounting (Annemans 2010) Furthermore, discounted costs would not reflect the actual amount that could be expected to be caused by the introduction of a new treatment (Marshall et al 2008) Discounting is also not recommended in the ISPOR guidelines, though it does not exclude the possibility to utilize discounting (Mauskopf et al 2007) Incorporation of treatment effect The minimum requirement in all budget impact analyses is to describe the differences in the treatment effect, adverse events, and usability The incorporation of the treatment effect in budget impact models is controversial In studies involving an acute health condition, this may be unnecessary However, in chronic diseases, treatment effect may be relevant to consider, as well as in cases where there is large variations in treatment costs depending on the stage of the disease Reporting results in budget impact analysis All studies should present results from a reference case, which includes the parameter values and assumptions that the authors consider to be most relevant and correct Nevertheless, the intention of budget impact analysis is not to give one absolutely correct value, but by definition, to “provide a range of predictions specific to that decisionmaker’s information needs” (Mauskopf et al 2007) This may be implemented by using a selection of sensitivity analyses Scenario analyses and one-way sensitivity analyses depict the range within where the true value would most likely lie The reporting of the results should enable the availability of results on a yearly basis, as well as over the entire study period Decomposition of results by cost types may be performed In addition, the results may be presented for distinct subpopulations However, the results should always include estimates related to the entire target population In budget impact analysis, the results of these sensitivity analyses should be reported side by side along with the base-case results Probabilistic sensitivity analysis In order to confer natural variation into the results, the use of a probabilistic sensitivity analysis (PSA) is recommended In PSA, all pre-defined model parameters are allowed to vary simultaneously according to their probability distributions The PSA results should then be depicted as affordability curves showing the probabilities that a treatment is affordable as a function of the budget constraint Timo Purmonen Pharmacoeconomic Methods for Estimating Cost-effectiveness and Budget Impact of Cancer Treatments in Finland The cost of cancer is increasing due to the ageing of the population, increased survival times and introduction of novel cancer treatments Economic evaluations are now being used to meet the challenges related to optimal allocation of scarce health care resources In this study, pharmacoeconomic methods were used to assess the quantity of health benefits gained with the resources invested in new cancer treatments, as well as the potential affordability of these treatments Publications of the University of Eastern Finland Dissertations in Health Sciences isbn 978-952-61-0858-2 ... supportive care CBA Cost- benefit analysis CEA Cost- effectiveness analysis CEAC Cost- effectiveness acceptability curve CER Cost- effectiveness ratio CMA Cost- minimization analysis CRD Centre for Reviews... COST OF CANCER IN FINLAND METHODS USED IN PHARMACOECONOMIC EVALUATION 4.1 Incremental cost- effectiveness ratio and willingness to pay threshold in a costeffectiveness... additional costs among the entire target population (Annemans 2010) 4.1 INCREMENTAL COST- EFFECTIVENESS RATIO AND WILLINGNESS TO PAY THRESHOLD IN A COST- EFFECTIVENESS ANALYSIS In a cost- effectiveness