TY  - JOUR
AB  - Background and Objective Although value sets for the five-level version of the generic health-related quality-of-life instrument EQ-5D are emerging, there is still no value set available in the literature based on time trade-off valuations made by individuals experiencing the valued health states. The aim of this study was to estimate experience-based value sets for the EQ-5D-5L for Sweden using time trade-off and visual analogue scale valuation methods. Methods In a large, cross-sectional, population-based, self-administered postal health survey, the EQ-5D-5L descriptive system, EQ visual analogue scale and a time trade-off question were included. Time trade-off and visual analogue scale valuations of the respondent's current health status were used in statistical modelling to estimate a single-index value of health for each of the 3125 health states. Ordinary least-squares and generalised linear models were estimated with the main effect within each of the five dimensions represented by 20 dummy variables reflecting the additional decrement in value for levels 2-5 when the severity increases by one level sequentially beginning from having no problem. Interaction variables representing the occurrence of severity levels in at least one of the dimensions were tested: severity level 2 or worse (N2); severity level 3 or worse (N3); severity level 4 or worse (N4); severity level 5 (N5). Results A total of 896 health states (28.7% of the 3125 possible EQ-5D-5L health states) were reported by the 25,867 respondents. Visual analogue scale (n = 23,899) and time trade-off (n = 13,381) responders reported valuations of their currently experienced health state. The preferred regression models used ordinary least-squares estimation for both time trade-off and visual analogue scale values and showed consistency in all coefficients after combining certain levels. Levels 4 and 5 for the dimensions of mobility, self-care and usual activities were combined in the time trade-off model. Including the interaction variable N5, indicating severity level 5 in at least one of the five dimensions, made it possible to distinguish between the two worst severity levels where no other dimension is at level 5 as this coefficient is applied only once. In the visual analogue scale regression model, levels 4 and 5 of the mobility dimension were combined. The interaction variables N2-N4 were included, indicating that each of these terms reflect a statistically significant decrement in visual analogue scale value if any of the dimensions is at severity level 2, 3 or 4, respectively. Conclusions Time trade-off and visual analogue scale value sets for the EQ-5D-5L are now available for Sweden. The time trade-off value set is the first such value set based on experience-based time trade-off valuation. For decision makers with a preference for experience-based valuations of health states from a representative population-based sample, the reported value sets may be considered fit for purpose to support resource allocation decision as well as evaluating population health and healthcare performance.
AU  - Burström, K.*
AU  - Teni, F.S.*
AU  - Gerdtham, U.G.*
AU  - Leidl, R.
AU  - Helgesson, G.*
AU  - Rolfson, O.*
AU  - Henriksson, M.*
C1  - 58879
C2  - 48411
CY  - 5 The Warehouse Way, Northcote 0627, Auckland, New Zealand
SP  - 839-856
TI  - Experience-based Swedish TTO and VAS value sets for EQ-5D-5L health states.
JO  - Pharmacoeconomics
VL  - 38
IS  - 8
PB  - Adis Int Ltd
PY  - 2020
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - In the context of an aging population with increasing diabetes prevalence, people are living longer with diabetes, which leads to increased multimorbidity and economic burden.The primary aim was to explore different strategies that address the economic impact of multiple type 2 diabetes-related complications and their interactions.We used a generalized estimating equations approach based on nationwide statutory health insurance data from 316,220 patients with type 2 diabetes (baseline year 2012, 3 years of follow-up). We estimated annual total costs (in 2015 euros) for type 2 diabetes-related complications and, in addition, explored different strategies to assess diabetes-related multimorbidity: number of prevalent complications, co-occurrence of micro- and macrovascular complications, disease-disease interactions of prevalent complications, and interactions between prevalent/incident complications.The increased number of complications was significantly associated with higher total costs. Further assessment of interactions showed that macrovascular complications (e.g., chronic heart failure) and high-cost complications (e.g., end-stage renal disease, amputation) led to significant positive effects of interactions on costs, whereas early microvascular complications (e.g., retinopathy) caused negative interactions. The chronology of the onset of these complications turned out to have an additional impact on the interactions and their effect on total costs.Health economic diabetes models and evaluations of interventions in patients with diabetes-related complications should pay more attention to the economic effect of specific disease interactions. Politically, our findings support the development of more integrated diabetes care programs that take better account of multimorbidity. Further observational studies are needed to elucidate the shared pathogenic mechanisms of diabetes complications.
AU  - Kähm, K.
AU  - Laxy, M.
AU  - Schneider, U.*
AU  - Holle, R.
C1  - 54225
C2  - 45301
CY  - 5 The Warehouse Way, Northcote 0627, Auckland, New Zealand
SP  - 63-74
TI  - Exploring different strategies of assessing the economic impact of multiple diabetes-associated complications and their interactions: A large claims-based in Germany.
JO  - Pharmacoeconomics
VL  - 37
IS  - 1
PB  - Adis Int Ltd
PY  - 2019
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - Background and Objective Accurate prediction of relevant outcomes is important for targeting therapies and to support health economic evaluations of healthcare interventions in patients with diabetes. The United Kingdom Prospective Diabetes Study (UKPDS) risk equations are some of the most frequently used risk equations. This study aims to analyze the calibration and discrimination of the updated UKPDS risk equations as implemented in the UKPDS Outcomes Model 2 (UKPDS-OM2) for predicting cardiovascular (CV) events and death in patients with type 2 diabetes mellitus (T2DM) from population-based German samples. Methods Analyses are based on data of 456 individuals diagnosed with T2DM who participated in two population-based studies in southern Germany (KORA (Cooperative Health Research in the Region of Augsburg)-A: 1997/1998, n = 178; KORA-S4: 1999-2001, n = 278). We compared the participants' 10-year observed incidence of mortality, CV mortality, myocardial infarction (MI), and stroke with the predicted event rate of the UKPDS-OM2. The model's calibration was evaluated by Greenwood-Nam-D'Agostino tests and discrimination was evaluated by C-statistics. Results Of the 456 participants with T2DM (mean age 65 years, mean diabetes duration 8 years, 56% male), over the 10-year follow-up time 129 died (61 due to CV events), 64 experienced an MI, and 46 a stroke. The UKPDS-OM2 significantly over-predicted mortality and CV mortality by 25% and 28%, respectively (Greenwood-Nam-D'Agostino tests: p < 0.01), but there was no significant difference between predicted and observed MI and stroke risk. The model poorly discriminated for death (C-statistic [95% confidence interval] = 0.64 [0.60-0.69]), CV death (0.64 [0.58-0.71]), and MI (0.58 [0.52-0.66]), and failed to discriminate for stroke (0.57 [0.47-0.66]). Conclusions The study results demonstrate acceptable calibration and poor discrimination of the UKPDS-OM2 for predicting death and CV events in this population-based German sample. Those limitations should be considered when using the UKPDS-OM2 for economic evaluations of healthcare strategies or using the risk equations for clinical decision-making.
AU  - Laxy, M.
AU  - Schöning, V.M.
AU  - Kurz, C.F.
AU  - Holle, R.
AU  - Peters, A.
AU  - Meisinger, C.
AU  - Rathmann, W.*
AU  - Mühlenbruch, K.*
AU  - Kähm, K.
C1  - 56648
C2  - 47168
CY  - 5 The Warehouse Way, Northcote 0627, Auckland, New Zealand
SP  - 1485-1494
TI  - Performance of the UKPDS outcomes model 2 for predicting death and cardiovascular events in patients with type 2 diabetes mellitus from a German Population-Based Cohort.
JO  - Pharmacoeconomics
VL  - 37
IS  - 12
PB  - Adis Int Ltd
PY  - 2019
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - Introduction: Etelcalcetide is a novel intravenous calcimimetic for the treatment of secondary hyperparathyroidism (SHPT) in haemodialysis patients. The clinical efficacy and safety of etelcalcetide (in addition to phosphate binders and vitamin D and/or analogues [PB/VD]) was evaluated in three phase III studies, including two placebo-controlled trials and a head-to-head study versus the oral calcimimetic cinacalcet. Objective: The objective of this study was to develop a decision-analytic model for economic evaluation of etelcalcetide compared with cinacalcet. Methods: We developed a life-time Markov model including potential treatment effects on mortality, cardiovascular events, fractures, and subjects’ persistence. Long-term efficacy of etelcalcetide was extrapolated from the reduction in parathyroid hormone (PTH) in the phase III trials and the available data from the outcomes study in cinacalcet (EVOLVE trial). Etelcalcetide was compared with cinacalcet, both in addition to PB/VD. We applied unit costs averaged from five European countries and a range of potential etelcalcetide pricing options assuming parity price to weekly use of cinacalcet and varying it by a 15 or 30% increase. Results: Compared with cinacalcet, the incremental cost-effectiveness ratio of etelcalcetide was €1,355 per QALY, €24,521 per QALY, and €47,687 per QALY for the three prices explored. The results were robust across the probabilistic and deterministic sensitivity analyses. Conclusions: Our modelling approach enabled cost-utility assessment of the novel therapy for SHPT based on the observed and extrapolated data. This model can be used for local adaptations in the context of reimbursement assessment.
AU  - Stollenwerk, B.
AU  - Iannazzo, S.*
AU  - Akehurst, R.*
AU  - Adena, M.*
AU  - Briggs, A.*
AU  - Dehmel, B.*
AU  - Parfrey, P.*
AU  - Belozeroff, V.*
C1  - 53083
C2  - 44319
SP  - 603-612
TI  - A decision-analytic model to assess the cost-effectiveness of etelcalcetide vs. cinacalcet.
JO  - Pharmacoeconomics
VL  - 36
IS  - 5
PY  - 2018
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - INTRODUCTION: Expert judgement has a role in model-based economic evaluations (EEs) of healthcare interventions. This study aimed to produce reporting criteria for two types of study design to use expert judgement in model-based EE: (i) an expert elicitation (quantitative) study; and (ii) a Delphi study to collate (qualitative) expert opinion. METHODS: A two-round online Delphi process identified the degree of consensus for four core definitions (expert; expert parameter values; expert elicitation study; expert opinion) and two sets of reporting criteria in a purposive sample of experts. The initial set of reporting criteria comprised 17 statements for reporting a study to elicit parameter values and/or distributions and 11 statements for reporting a Delphi survey to obtain expert opinion. Fifty experts were invited to become members of the Delphi process panel by e-mail. Data analysis summarised the extent of agreement (using a pre-defined 75 % 'consensus' threshold) on the definitions and suggested reporting criteria. Free-text comments were analysed using thematic analysis. RESULTS: The final panel comprised 12 experts. Consensus was achieved for the definitions of expert (88 %); expert parameter values (83 %); and expert elicitation study (83 %). The panel recommended criteria to use when reporting an expert elicitation study (16 criteria) and a Delphi study to collate expert opinion (11 criteria). CONCLUSION: This study has produced guidelines for reporting two types of study design to use expert judgement in model-based EE: (i) an expert elicitation study requiring 16 reporting criteria; and (ii) a Delphi study to collate expert opinion requiring 11 reporting criteria.
AU  - Iglesias, C.P.*
AU  - Thompson, A.*
AU  - Rogowski, W.H.
AU  - Payne, K.*
C1  - 49024
C2  - 41554
CY  - Northcote
SP  - 1161-1172
TI  - Reporting guidelines for the use of expert judgement in model-based economic evaluations.
JO  - Pharmacoeconomics
VL  - 34
IS  - 11
PB  - Adis Int Ltd
PY  - 2016
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - OBJECTIVE: The aim of this study was to assess the cost effectiveness of the novel fixed-dose anticoagulant rivaroxaban compared with the current standard of care, warfarin, for the prevention of stroke in patients with atrial fibrillation (AF). METHODS: A Markov model was constructed to model the costs and health outcomes of both treatments, potential adverse events, and resulting health states over 35 years. Analyses were based on a hypothetical cohort of 65-year-old patients with non-valvular AF at moderate to high risk of stroke. The main outcome measure was cost per quality-adjusted life-year (QALY) gained over the lifetime, and was assessed from the German Statutory Health Insurance (SHI) perspective. Costs and utility data were drawn from public data and the literature, while event probabilities were derived from both the literature and rivaroxaban's pivotal ROCKET AF trial. RESULTS: Stroke prophylaxis with rivaroxaban offers health improvements over warfarin treatment at additional cost. From the SHI perspective, at baseline the incremental cost-effectiveness ratio of rivaroxaban was 15,207 per QALY gained in 2014. The results were robust to changes in the majority of variables; however, they were sensitive to the price of rivaroxaban, the hazard ratios for stroke and intracranial hemorrhage, the time horizon, and the discount rate. CONCLUSIONS: Our results showed that the substantially higher medication costs of rivaroxaban were offset by mitigating the shortcomings of warfarin, most notably frequent dose regulation and bleeding risk. Future health economic studies on novel oral anticoagulants should evaluate the cost effectiveness for secondary stroke prevention and, as clinical data from direct head-to-head comparisons become available, new anticoagulation therapies should be compared against each other.
AU  - Mensch, A.*
AU  - Stock, S.*
AU  - Stollenwerk, B.
AU  - Müller, D.*
C1  - 42842
C2  - 35417
CY  - Northcote
SP  - 271-283
TI  - Cost effectiveness of rivaroxaban for stroke prevention in German patients with atrial fibrillation.
JO  - Pharmacoeconomics
VL  - 33
IS  - 3
PB  - Adis Int Ltd
PY  - 2015
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - CONTEXT: This study assesses if, and how, existing methods for economic evaluation are applicable to the evaluation of personalized medicine (PM) and, if not, where extension to methods may be required. METHODS: A structured workshop was held with a predefined group of experts (n = 47), and was run using a modified nominal group technique. Workshop findings were recorded using extensive note taking, and summarized using thematic data analysis. The workshop was complemented by structured literature searches. RESULTS: The key finding emerging from the workshop, using an economic perspective, was that two distinct, but linked, interpretations of the concept of PM exist (personalization by 'physiology' or 'preferences'). These interpretations involve specific challenges for the design and conduct of economic evaluations. Existing evaluative (extra-welfarist) frameworks were generally considered appropriate for evaluating PM. When 'personalization' is viewed as using physiological biomarkers, challenges include representing complex care pathways; representing spillover effects; meeting data requirements such as evidence on heterogeneity; and choosing appropriate time horizons for the value of further research in uncertainty analysis. When viewed as tailoring medicine to patient preferences, further work is needed regarding revealed preferences, e.g. treatment (non)adherence; stated preferences, e.g. risk interpretation and attitude; consideration of heterogeneity in preferences; and the appropriate framework (welfarism vs. extra-welfarism) to incorporate non-health benefits. CONCLUSIONS: Ideally, economic evaluations should take account of both interpretations of PM and consider physiology and preferences. It is important for decision makers to be cognizant of the issues involved with the economic evaluation of PM to appropriately interpret the evidence and target future research funding.
AU  - Rogowski, W.H.
AU  - Payne, K.*
AU  - Schnell-Inderst, P.*
AU  - Manca, A.*
AU  - Rochau, U.*
AU  - Jahn, B.*
AU  - Alagoz, O.*
AU  - Leidl, R.
AU  - Siebert, U.*
C1  - 32370
C2  - 35013
SP  - 49-59
TI  - Concepts of 'personalization' in personalized medicine: Implications for economic evaluation.
JO  - Pharmacoeconomics
VL  - 33
IS  - 1
PY  - 2015
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - BACKGROUND: Lung cancer is among the top causes of cancer-related deaths. Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors can increase progression-free survival compared with standard chemotherapy in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). OBJECTIVE: The aim of the study was to evaluate the cost-effectiveness of EGFR mutation analysis and first-line therapy with erlotinib for mutation-positive patients compared with non-individualized standard chemotherapy from the perspective of German statutory health insurance. METHODS: A state transition model was developed for a time horizon of 10 years (reference year 2014). Data sources were published data from the European Tarceva versus Chemotherapy (EURTAC) randomized trial for drug efficacy and safety and German cost data. We additionally performed deterministic, probabilistic and structural sensitivity analyses. RESULTS: The individualized strategy incurred 0.013 additional quality-adjusted life-years (QALYs) and additional costs of 200, yielding an incremental cost-effectiveness ratio (ICER) of 15,577/QALY. Results were most sensitive to uncertainty in survival curves and changes in utility values. Cross-validating health utility estimates with recent German data increased the ICER to about 58,000/QALY. The probabilistic sensitivity analysis indicated that the individualized strategy is cost-effective, with a probability exceeding 50 % for a range of possible willingness-to-pay thresholds. LIMITATIONS: The uncertainty of the predicted survival curves is substantial, particularly for overall survival, which was not a primary endpoint in the EURTAC study. Also, there is limited data on quality of life in metastatic lung cancer patients. CONCLUSIONS: Individualized therapy based on EGFR mutation status has the potential to provide a cost-effective alternative to non-individualized care for patients with advanced adenocarcinoma. Further clinical research is needed to confirm these results.
AU  - Schremser, K.
AU  - Rogowski, W.H.
AU  - Adler-Reichel, S.*
AU  - Tufman, A.L.*
AU  - Huber, R.M.
AU  - Stollenwerk, B.
C1  - 45335
C2  - 37282
SP  - 1215-1228
TI  - Cost-effectiveness of an individualized first-line treatment strategy offering erlotinib based on EGFR mutation testing in advanced lung adenocarcinoma patients in Germany.
JO  - Pharmacoeconomics
VL  - 33
IS  - 11
PY  - 2015
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - Background: Individualized medicine (IM) is a rapidly evolving field that is associated with both visions of more effective care at lower costs and fears of highly priced, low-value interventions. It is unclear which view is supported by the current evidence. Objective: Our objective was to systematically review the health economic evidence related to IM and to derive general statements on its cost-effectiveness. Data sources: A literature search of MEDLINE database for English- and German-language studies was conducted. Study appraisal and synthesis method: Cost-effectiveness and cost-utility studies for technologies meeting the MEDLINE medical subject headings (MeSH) definition of IM (genetically targeted interventions) were reviewed. This was followed by a standardized extraction of general study characteristics and cost-effectiveness results. Results: Most of the 84 studies included in the synthesis were from the USA (n = 43, 51 %), cost-utility studies (n = 66, 79 %), and published since 2005 (n = 60, 71 %). The results ranged from dominant to dominated. The median value (cost-utility studies) was calculated to be rounded $US22,000 per quality-adjusted life year (QALY) gained (adjusted to $US, year 2008 values), which is equal to the rounded median cost-effectiveness in the peer-reviewed English-language literature according to a recent review. Many studies reported more than one strategy of IM with highly varying cost-effectiveness ratios. Generally, results differed according to test type, and tests for disease prognosis or screening appeared to be more favorable than tests to stratify patients by response or by risk of adverse effects. However, these results were not significant. Limitations: Different definitions of IM could have been used. Quality assessment of the studies was restricted to analyzing transparency. Conclusions: IM neither seems to display superior cost-effectiveness than other types of medical interventions nor to be economically inferior. Instead, rather than 'whether' healthcare was individualized, the question of 'how' it was individualized was of economic relevance.
AU  - Hatz, M.H.M.
AU  - Schremser, K.
AU  - Rogowski, W.H.
C1  - 30698
C2  - 33822
CY  - Auckland
SP  - 443-455
TI  - Is individualized medicine more cost-effective? A systematic review.
JO  - Pharmacoeconomics
VL  - 32
IS  - 5
PB  - Adis Int Ltd
PY  - 2014
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - Background: Thrombosis inhibitors can be used to treat acute coronary syndromes (ACS). However, there are various alternative treatment strategies, of which some have been compared using health economic decision models. Objective: To assess the quality of health economic decision models comparing thrombosis inhibitors in patients with ACS undergoing percutaneous coronary intervention, and to identify areas for quality improvement. Data Sources: The literature databases MEDLINE, EMBASE, EconLit, National Health Service Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). Study Appraisal and Synthesis Methods: A review of the quality of health economic decision models was conducted by two independent reviewers, using the Philips checklist. Results: Twenty-one relevant studies were identified. Differences were apparent regarding the model type (six decision trees, four Markov models, eight combinations, three undefined models), the model structure (types of events, Markov states) and the incorporation of data (efficacy, cost and utility data). Critical issues were the absence of particular events (e.g. thrombocytopenia, stroke) and questionable usage of utility values within some studies. Limitations: As we restricted our search to health economic decision models comparing thrombosis inhibitors, interesting aspects related to the quality of studies of adjacent medical areas that compared stents or procedures could have been missed. Conclusions: This review identified areas where recommendations are indicated regarding the quality of future ACS decision models. For example, all critical events and relevant treatment options should be included. Models also need to allow for changing event probabilities to correctly reflect ACS and to incorporate appropriate, age-specific utility values and decrements when conducting cost-utility analyses.
AU  - Hatz, M.H.M.
AU  - Leidl, R.
AU  - Yates, N.A.
AU  - Stollenwerk, B.
C1  - 30577
C2  - 33715
CY  - Auckland
SP  - 377-393
TI  - A systematic review of the quality of economic models comparing thrombosis inhibitors in patients with acute coronary syndrome undergoing percutaneous coronary intervention.
JO  - Pharmacoeconomics
VL  - 32
IS  - 4
PB  - Adis Int Ltd
PY  - 2014
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - Background: Cystic fibrosis (CF) is the most common life-shortening genetic disorder among Whites worldwide. Because many of these patients experience chronic endobronchial colonization and have to take antibiotics and be treated as inpatients, societal costs of CF may be high. As the disease severity varies considerably among patients, costs may differ between patients. Objectives: Our objectives were to calculate the average total costs of CF per patient and per year from a societal perspective; to include all direct medical and non-medical costs as well as indirect costs; to identify the main cost drivers; to investigate whether patients with CF can be grouped into homogenous cost groups; and to determine the influence of specific factors on different cost categories. Methods: Resource utilization data were collected for 87 patients admitted to an inpatient unit at a CF treatment centre during the first 6 months of 2004 and 125 patients who visited the centre's CF outpatient unit during the entire year. Fifty-four patients were admitted to the hospital and also visited the outpatient unit. Since all patients were exclusively treated at the centre, data could be aggregated. Costs that varied greatly between patients were measured per patient. The remaining costs were summarized as overhead costs and allocated on the basis of days of treatment or contacts per patient. Costs of the outpatient and inpatient units and costs for drugs patients received at the outpatient pharmacy were summarized as direct medical costs. Direct non-medical costs (i.e. travel expenses), as well as indirect costs (i. e. absence from work, productivity losses), were also included in the analysis. Main cost drivers were detected by the analysis of different cost categories. Patients were classified according to a diagnosis-related severity model, and median comparison tests (Wilcoxon-Mann-Whitney tests) were performed to investigate differences between the severity groups. Generalized least squares (GLS) regressions were used to identify variables influencing different cost categories. A sensitivity analysis using Monte Carlo simulation was performed. Results: The mean total cost per patient per year was 41 468 (year 2004 values). Direct medical costs accounted for more than 90% of total costs and averaged (sic)38 869 ((sic)3876 to (sic)88 096), whereas direct non-medical costs were minimal. Indirect costs amounted to (sic)2491 (6% of total costs). Costs for drugs patients received at the outpatient pharmacy were the main cost driver. Costs rose with the degree of severity. Patients with moderate and severe disease had significantly hieher direct costs than the relatively milder group. Regression analysis revealed that direct costs were mainly affected by the diagnosis-related severity level and the expiratory volume; the coefficient indicating the relationship between costs for mild CF patients and other patients rose with the degree of severity. A similar result was obtained for drug costs per patient as the dependent variable. Monte Carlo simulation suggests that there is a 90% probability that annual costs will be lower than (sic)37 300. Conclusions: The share of indirect costs as a percentage of total costs for CF was rather low in this study. However, the relevance of indirect costs is likely to increase in the future as the life expectancy of CF patients increases, which is likely to lead to a rising work disability rate and thus increase indirect costs. Moreover we found that infection with Pseudomonas aeruginosa increases costs substantially. Thus, a decrease of the prevalence of P. aeruginosa would lead to substantial savings for society.
AU  - Heimeshoff, M.*
AU  - Hollmeyer, H.*
AU  - Schreyögg, J.
AU  - Tiemann, O.
AU  - Staab, D.*
C1  - 10415
C2  - 30567
SP  - 763-777
TI  - Cost of illness of cystic fibrosis in Germany: Results from a large cystic fibrosis centre.
JO  - Pharmacoeconomics
VL  - 30
IS  - 9
PB  - Adis Int. Ltd.
PY  - 2012
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - Background: Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death worldwide. It has serious health effects and causes substantial costs for society. Objectives: The aim of the present paper was to develop a state-of-the-art decision-analytic model of COPD whereby the cost effectiveness of interventions in Germany can be estimated. To demonstrate the applicability of the model, a smoking cessation programme was evaluated against usual care. Methods: A seven-stage Markov model (disease stages I to IV according to the GOLD [Global Initiative for Chronic Obstructive Lung Disease] classification, states after lung-volume reduction surgery and lung transplantation, death) was developed to conduct a cost-utility analysis from the societal perspective over a time horizon of 10, 40 and 60 years. Patients entered the cohort model at the age of 45 with mild COPD. Exacerbations were classified into three levels: mild, moderate and severe. Estimation of stage-specific probabilities (for smokers and quitters), utilities and costs was based on German data where possible. Data on effectiveness of the intervention was retrieved from the literature. A discount rate of 3% was applied to costs and effects. Probabilistic sensitivity analysis was used to assess the robustness of the results. Results: The smoking cessation programme was the dominant strategy compared with usual care, and the intervention resulted in an increase in health effects of 0.54 QALYs and a cost reduction of €1115 per patient (year 2007 prices) after 60 years. In the probabilistic analysis, the intervention dominated in about 95% of the simulations. Sensitivity analyses showed that uncertainty primarily originated from data on disease progression and treatment cost in the early stages of disease. Conclusions: The model developed allows the long-term cost effectiveness of interventions to be estimated, and has been adapted to Germany. The model suggests that the smoking cessation programme evaluated was more effective than usual care as well as being cost-saving. Most patients had mild or moderate COPD, stages for which parameter uncertainty was found to be high. This raises the need to improve data on the early stages of COPD.
AU  - Menn, P.
AU  - Leidl, R.
AU  - Holle, R.
C1  - 8354
C2  - 30071
SP  - 825-840
TI  - A lifetime Markov model for the economic evaluation of chronic obstructive pulmonary disease.
JO  - Pharmacoeconomics
VL  - 30
IS  - 9
PB  - Adis Int. Ltd.
PY  - 2012
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - BACKGROUND: Market authorization does not guarantee patient access to any given drug. This is particularly true for costly orphan drugs because access depends primarily on co-payments, reimbursement policies and prices. The objective of this article is to identify differences in the availability of orphan drugs and in patient access to them in 11 pharmaceutical markets: Australia, Canada, England, France, Germany, Hungary, the Netherlands, Poland, Slovakia, Switzerland and the US. METHODS: Four rare diseases were selected for analysis: pulmonary arterial hypertension (PAH), Fabry disease (FD), hereditary angioedema (HAE) and chronic myeloid leukaemia (CML). Indicators for availability were defined as (i) the indications for which orphan drugs had been authorized in the treatment of these diseases; (ii) the application date; and (iii) the date upon which these drugs received market authorization in each country. Indicators of patient access were defined as (i) the outcomes of technology appraisals; (ii) the extent of coverage provided by healthcare payers; and (iii) the price of the drugs in each country. For PAH we analysed bosentan, iloprost, sildenafil, treprostinil (intravenous and inhaled) as well as sitaxentan and ambrisentan; for FD we analysed agalsidase alfa and agalsidase beta; for HAE we analysed icatibant, ecallantide and two complement C1s inhibitors; for CML we analysed imatinib, dasatinib and nilotinib. RESULTS: Most drugs included in this study had received market authorization in all countries, but the range of indications for which they had been authorized differed by country. The broadest range of indications was found in Australia, and the largest variations in indications were found for PAH drugs. Authorization process speed (the time between application and market authorization) was fastest in the US, with an average of 362 days, followed by the EU (394 days). The highest prices for the included drugs were found in Germany and the US, and the lowest in Canada, Australia and England. Although the prices of all of the included drugs were high compared with those of most non-orphan drugs, most of the insurance plans in our country sample provided coverage for authorized drugs after a certain threshold. CONCLUSIONS: Availability of and access to orphan drugs play a key role in determining whether patients will receive adequate and efficient treatment. Although the present study showed some variations between countries in selected indicators of availability and access to orphan drugs, virtually all of the drugs in question were available and accessible in our sample. However, substantial co-payments in the US and Canada represent important barriers to patient access, especially in the case of expensive treatments such as those analysed in this study. Market exclusivity is a strong instrument for fostering orphan drug development and drug availability. However, despite the positive effect of this instrument, the conditions under which market exclusivity is granted should be reconsidered in cases where the costs of developing an orphan drug have already been amortized through the use of the drug's active ingredient for the treatment of a common indication.
AU  - Blankart, C.R.B.
AU  - Stargardt, T.
AU  - Schreyögg, J.
C1  - 4697
C2  - 28285
SP  - 63-82
TI  - Availability of and access to orphan drugs: An international comparison of pharmaceutical treatments for pulmonary arterial hypertension, Fabry disease, hereditary angioedema and chronic myeloid leukaemia.
JO  - Pharmacoeconomics
VL  - 29
IS  - 1
PB  - Adis Data Information
PY  - 2011
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - BACKGROUND: Decision makers responsible for allocation of healthcare resources may require that health states are valued by the population for whom they are making decisions. To achieve this, health-state descriptions can be combined with a value set that reflects the valuations of the target population. In the decision-utility approach, such a value set is at least partly based on wants and expectations regarding given health states. This may reflect aspects different from the health state experienced and valued by a respondent. OBJECTIVES: To derive a value set that is completely based on experienced health states, emphasising the patient's perspective, and test its predictive performance in comparison with established approaches. METHODS: Problem descriptions and rating scale valuations of the EQ-5D were drawn from two representative German population surveys in 2006 and 2007. Two models based on given health states but differing in valuation method (1a, b) were analysed, along with three models based on experienced health states: (2) ordinary least squares regression; (3) scale-transformed regression; and (4) a generalized linear model with binomial error distribution and constraint parameter estimation. The models were compared with respect to issues in specification, and accuracy in predicting the actual valuations of experienced health states in a new data set, using correlation, mean error and ranking measures for the latter. In addition, the impact of standardizing experience-based index models for age and sex of the subjects was investigated. RESULTS: Models 1 (a, b), 2 and 3 partly led to plausible and comparable parameter estimates, but also led to problems of insignificance and inconsistencies in some of the estimates. Model 4 achieved consistency and featured partly equivalent and partly better predictive accuracy. Using this model, mean valuations of health states were much better predicted by the experience-based approach than by the decision-utility approach, especially for health states that frequently (>10) occurred in the population sample. Standardizing the experience-based index models for age and sex further improved predictive accuracy and strengthened the position of model 4. CONCLUSIONS: A value set for the EQ-5D can be plausibly estimated from experience-based valuations. The approach offers an alternative to decision makers who prefer experience-based valuation over decision utilities in the measurement of health outcome. Although usefulness in population samples was shown, use in a clinical context will first require indication-specific tests. Current limitations include use in a general population only, and a restricted range of health states covered.
AU  - Leidl, R.
AU  - Reitmeir, P.
C1  - 6430
C2  - 28669
SP  - 521-534
TI  - A value set for the EQ-5D based on experienced health states: Development and testing for the German population.
JO  - Pharmacoeconomics
VL  - 29
IS  - 6
PB  - Adis Int Ltd.
PY  - 2011
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - BACKGROUND: Various software packages are commonly used for the implementation and calculation of decision-analytic models for health economic evaluations. However, comparison of these programs with regard to ease of implementing a model is lacking. OBJECTIVES: (i) to compare the assets and drawbacks of three commonly used software packages for Markov models with regard to ease of implementation; and (ii) to investigate how a technical model validation can be conducted by comparing the results of the three implementations. METHODS: A Markov model on chronic obstructive pulmonary disease was implemented in TreeAge, Microsoft Excel and Arena with the same assumptions on model structure, transition probabilities and costs. A hypothetical smoking cessation programme for patients in stage 1 was evaluated against usual care. The packages were compared with respect to time and effort for implementation, run-time, features for the presentation of results, and flexibility. Agreement between the packages on average costs and life-years gained and on the incremental cost-effectiveness ratio was considered for technical validation in the form of expected values (between TreeAge and Excel only) and Monte Carlo simulations. RESULTS: Ease of implementation was best in TreeAge, whereas Arena offered the highest flexibility. Deterministic results were in agreement between TreeAge and Excel, as were simulated values between all three packages. CONCLUSIONS: Excel offers an intuitive spreadsheet interface, but the acquisition of and the training in TreeAge or Arena is worthwhile for more complex models. Double implementation is a practicable validation technique that should be conducted to ensure correct model implementation.
AU  - Menn, P.
AU  - Holle, R.
C1  - 2257
C2  - 26670
SP  - 745-753
TI  - Comparing three software tools for implementing markov models for health economic evaluations.
JO  - Pharmacoeconomics
VL  - 27
IS  - 9
PB  - Adis Data Information BV
PY  - 2009
SN  - 1170-7690
ER  - 

TY  - JOUR
AB  - Osteoporosis is a frequent complication in patients with inflammatory bowel disease. Recent studies have shown bisphosphonates to considerably reduce fracture risk in patients with osteoporosis, and preventing fractures with bisphosphonates has been reported to be cost effective in older populations. However, no studies of the cost effectiveness of these agents in preventing fractures in patients with inflammatory bowel disease are available. OBJECTIVE: To investigate the cost effectiveness of the bisphosphonate ibandronate combined with calcium/colecalciferol ('ibandronate') in patients with osteopenia or osteoporosis due to inflammatory bowel disease in Germany. Treatment strategies used for comparison were sodium fluoride combined with calcium/colecalciferol ('fluoride') and calcium/colecalciferol ('calcium') alone. STUDY DESIGN AND METHODS: A cost-utility analysis was conducted using data from a randomized controlled trial (RCT). Changes in bone mineral density (BMD) were adjusted and predicted for a standardized population receiving each respective treatment. A Markov model was developed, with probabilities of transition to fracture states consisting of BMD-dependent and -independent components. The BMD-dependent component was assessed using predicted change in BMD from the RCT. The independent component captured differences in bone quality and micro-architecture resulting from prevalent fractures or treatment with anti-resorptive drugs.The analysis was conducted for a population with a mean age of the RCT patients (women aged 36 years, men aged 38 years) with osteopenia (T-score about -2.0 at baseline), a population of the same age with osteoporosis (T-score of -3.0 at baseline) and for an older population (both sexes aged 65 years) with osteoporosis (T-score of -3.0). Outcomes were measured as costs per QALY gained from a societal perspective. The treatment duration in the RCT was 42 months. A 5-year period was assumed to follow, during which the treatment effects linearly declined to 0. The simulation time was 10 years.Prices for medication and treatment were presented as year 2004 values; costs and effects were discounted at 5%. To test the robustness of the results, univariate and probabilistic sensitivity analyses (Monte Carlo simulation) were conducted. RESULTS: The calcium strategy dominated the fluoride strategy. When the ibandronate strategy was compared with the calcium strategy, the base-case cost-effectiveness ratios (costs per QALY gained) were between euro 407 375 for an older female population with osteoporosis and euro 6 516 345 for a younger female population with osteopenia. Univariate sensitivity analyses resulted in variations between 4% of base-case results and dominance of calcium. In Monte Carlo simulations, conducted for the various populations, the probability of an ICER of ibandronate below euro 50 000 per QALY was never greater than 20.2%. CONCLUSION: The ibandronate strategy is unlikely to be considered cost effective by decision makers in men or women with characteristics of those in the target population of the RCT, or in older populations with osteoporosis.
AU  - Kreck, S.*
AU  - Klaus, J.*
AU  - Leidl, R.
AU  - von Tirpitz, C.*
AU  - Konnopka, A.*
AU  - Matschinger, H.*
AU  - König, H.H.*
C1  - 2657
C2  - 25684
SP  - 311-328
TI  - Cost effectiveness of ibandronate for the prevention of fractures in inflammatory bowel disease-related osteoporosis: Cost-utility analysis using a Markov model.
JO  - Pharmacoeconomics
VL  - 26
IS  - 4
PB  - Wolters Kluwer Health Adis
PY  - 2008
SN  - 1170-7690
ER  - 

TY  - JOUR
AU  - Bos, J.M.*
AU  - Rümke, H.C.*
AU  - Welte, R.
AU  - Spanjaard, L.*
AU  - van Alphen, L.*
AU  - Postma, M.J.*
C1  - 4708
C2  - 23502
SP  - 141-153
TI  - Combination vaccine against invasive meningococcal B and pneumococcal infections: Potential epidemiological and economic impact in The Netherlands.
JO  - Pharmacoeconomics
VL  - 24
PY  - 2006
SN  - 1170-7690
ER  - 

TY  - JOUR
AU  - Stark, R.G.
AU  - König, H.-H.*
AU  - Leidl, R.
C1  - 4978
C2  - 24077
SP  - 797-814
TI  - Costs of inflammatory bowel disease in Germany.
JO  - Pharmacoeconomics
VL  - 24
PY  - 2006
SN  - 1170-7690
ER  - 

TY  - JOUR
AU  - Welte, R.
AU  - Trotter, C.*
AU  - Edmunds, W.*
AU  - Postma, M.J.*
AU  - Beutels, P.*
C1  - 4849
C2  - 23167
SP  - 855-874
TI  - The Role of Economic Evaluation in Vaccine Decision Making.
JO  - Pharmacoeconomics
VL  - 23
PY  - 2005
SN  - 1170-7690
ER  - 

TY  - JOUR
AU  - Welte, R.
AU  - Feenstra, T.*
AU  - Jager, H.*
AU  - Leidl, R.
C1  - 3802
C2  - 21951
SP  - 857-876
TI  - A decision chart for assessing and improving the transferability of economic evaluation results between countries.
JO  - Pharmacoeconomics
VL  - 22
PY  - 2004
SN  - 1170-7690
ER  -