Ej Soini

Cost–utility of different treatment strategies after the failure of tumour necrosis factor inhibitor in rheumatoid arthritis in the Finnish setting

Objective. To evaluate the cost–utility of different treatment strategies in severe RA after TNF-inhibitor failure. Methods. The cost-effectiveness of treatment strategies was compared in a group of hypothetical Finnish RA patients. Initially, the patients received either best supportive care (BSC) or one of the following treatments before BSC: adalimumab (ADAL), abatacept (ABAT), etanercept (ETAN), infliximab (INFL) or rituximab (RTX). Further treatments were added to the most cost-effective strategy in a stepwise manner. The analysis was performed on an Excel-based Markov state transition model using the probabilistic approach. The clinical outcomes related to treatments were estimated from published clinical trials. The gained quality-adjusted life-years (QALYs) were estimated based on Health Utilities Index (HUI-3) and disease severity scores (HAQ). The resource use and costs were obtained from the Finnish treatment practice, one published study, the Finnish Unit Cost list and Finnish Medicine Tariffs. Results. Treatment with RTX was more effective and less costly than treatment with ADAL, ABAT or ETAN after TNF-inhibitor failure. An additional QALY gained with RTX costs 30 248 euros compared with BSC. The incremental cost-effectiveness ratios (ICERs) are 50 941, 50 372, 36 121 and 67 003 euros per QALY gained for adding ADAL, ETAN, INFL and ABAT to the RTX strategy, respectively. According to the cost-effectiveness acceptability frontier (CEAF), only BSC or treatments with RTX or RTX followed by INFL should be considered after TNF-inhibitor failure, if willingness to pay is between 0 and 50 000 euros per QALY gained. Conclusions. Treatment with RTX is a cost-effective treatment strategy in RA patients in Finland.

Cost-effectiveness of adalimumab, etanercept, and tocilizumab as first-line treatments for moderate-to-severe rheumatoid arthritis.

Abstract Objective: The aim of this study was to assess the cost-utility and value of reducing the uncertainty associated with the decision to use first-line biologic treatment (bDMARD) after the failure of one or more traditional drugs (tDMARD) in moderate-to-severe rheumatoid arthritis (msRA) in Finland. Research design and methods: The treatment sequences were compared among 3000 hypothetical Finnish msRA patients using a probabilistic microsimulation model in a lifetime scenario. Adalimumab + methotrexate, etanercept + methotrexate, or tocilizumab + methotrexate were used as first biologics followed by rituximab + methotrexate and infliximab + methotrexate. Best supportive care (BSC), including tDMARDs, was assumed to be used after the exhaustion of the biologics. Methotrexate alone was added as a further comparator. Efficacy was based on ACR responses that were obtained from a mixed treatment comparison. The resources were valued with Finnish unit costs (year 2010) from the healthcare payer perspective. Additional analyses were carried out, including productivity losses. The Health Assessment Questionnaire (HAQ) values were mapped to the EQ-5D values using the tocilizumab trials; 3% annual discounting for costs and quality-adjusted life years (QALY) and extensive sensitivity analyses were completed. Main outcome measures: Incremental cost per QALY gained and multinomial expected value of perfect information (mEVPI). Results: bDMARDs significantly increase the QALYs gained when compared to methotrexate alone. Tocilizumab + methotrexate was more cost-effective than adalimumab + methotrexate or etanercept + methotrexate in comparison with methotrexate alone, and adalimumab + methotrexate was dominated by etanercept + methotraxate. A QALY gained with retail-priced (wholesale-priced) tocilizumab + methotrexate costs €18,957 (€17,057) compared to methotrexate alone. According to the cost-effectiveness efficiency frontier and cost-effectiveness acceptability frontier (CEAF), tocilizumab + methotrexate should be considered before rituximab + methotrexate, infliximab + methotrexate, and BSC. Based on the CEAF, tocilizumab + methotrexate had a 60–93% probability of being cost-effective with €20,000 per QALY gained (mEVPI €230–2182). Conclusions: Tocilizumab + methotrexate is a potentially cost-effective bDMARD treatment for msRA, indicating a low value of additional research information with the international threshold values. Limitations: Efficacy based on an indirect comparison (certolizumab pegol, golimumab excluded), fixed treatment sequence after the exhaustion of first bDMARD, Swedish resource use data according to HAQ scores, and inpatient costs assumed to include surgery.

Economic evaluation of sunitinib malate in second-line treatment of metastatic renal cell carcinoma in Finland

BACKGROUND Cytokine therapy is currently used as first-line treatment of metastatic renal cell carcinoma (mRCC). Until recently, treatments with proven efficacy after the failure of first-line cytokine therapy were not available. In recent clinical trials, sunitinib has been associated with good response rates in patients with mRCC. OBJECTIVE The aim of this study was to analyze the cost-effectiveness of sunitinib as second-line therapy for cytokine-refractory mRCC compared with current routine clinical practice in Finland (ie, best supportive care [BSC], including palliative biochemotherapy). METHODS A probabilistic decision-analytic model was developed to estimate the cost-effectiveness of sunitinib. Data were gathered from clinical trials, literature sources, and expert opinions, as well as from a local sample (n = 39) from 2 university hospitals in Finland. Clinical experts treating patients with mRCC in Finland provided the information on care practices of prescribing sunitinib. The analysis was conducted from the perspective of the health care payer in Finland. RESULTS According to estimated incremental cost-effectiveness ratios (ICERs), 1 progression-free month gained cost euro4802 (2005 Euros); 1 life-year gained cost euro30,831; and 1 quality-adjusted life-year (QALY) gained cost euro43,698, compared with BSC, in the treatment of mRCC. The expected mean cost in BSC was euro5543. When parameter uncertainty was considered, the probability of sunitinib being the more cost-effective choice of treatment was ~70% at the willingness-to-pay level of euro45,000/QALY gained. CONCLUSIONS Based on the results of this cost-effectiveness analysis, sunitinib is potentially cost-effective as a second-line treatment of mRCC compared with the treatment currently practiced in Finnish hospitals. The ICER (euro/QALY gained) obtained in the present study was less than the value considered suitable for novel oncology treatments.

Risk factors for persistent frequent use of the primary health care services among frequent attenders: A Bayesian approach

Abstract Objectives . The aim of this study was to examine risk factors that predict persistent healthcare frequent attendance among a frequent attender (FA) population. Design. Prospective cohort study without intervention. Setting. Primary healthcare centre in Tampere, Finland. Subjects. A total of 85 primary healthcare working-age patients participated in the study. All participants were FAs in the first study year. Main outcome measures. We identified two groups of patients: temporary FAs and persistent FAs. A patient was considered as a persistent FA if he or she visited the health centre at least eight times a year for at least three out of four follow-up years. Some 59 different variables were examined as potential risk factors for persistent FA. P-course, a web-based Na ï ve Bayesian classification tool, was used for the modelling of the data. Results. In our model, the most influential predictive risk factors for persistent frequent attendance in an FA population were female gender, body mass index above 30, former frequent attendance, fear of death, alcohol abstinence, low patient satisfaction, and irritable bowel syndrome. New observations were high body mass index, alcohol abstinence, irritable bowel syndrome, low patient satisfaction, and fear of death. Conclusions. In FA analyses, distinction between temporary and persistent frequent attendance should be made. Our Bayesian model could be used for identifying persistent FAs in uncertain situations. The model can quite easily be further developed as a practical decision support tool for general practitioners. However, before its use in practice, the external validity of the model will need to be defined.

Cost-effectiveness of statins in the prevention of coronary heart disease events in middle-aged Finnish men

ABSTRACT Objective: This study evaluated the long-term cost-effectiveness of atorvastatin 20 mg, rosuvastatin 10 mg and simvastatin 40 mg in primary and secondary prevention of CHD in Finland. Research design and methods: The effect of statin therapy on the incidence of CHD and the expected total costs of the disease were described using a Markov state transition model. Due to the limited amount of evidence concerning mortality and morbidity for rosuvastatin, the model was used to transmute the efficiency data of all statins (decrease in total cholesterol) into long-term endpoints (myocardial infarction, death) using risk functions of the FINRISK and 4S studies. The study followed a characterized cohort of 55-year-old Finnish men with an average 3.3–6.6 % baseline risk of dying from cardiovascular disease within a 10-year period. Main outcome measures: Incremental cost-effectiveness ratios (ICERs) for atorvastatin and rosuvastatin, compared with simvastatin, measured as cost of life years gained (€/LYG) and cost of quality adjusted life years gained (€/QALY). Results: The use of rosuvastatin increased the life expectancy by 0.27 years on average (LYG) compared with simvastatin, producing additional 0.08 quality-adjusted life-years (QALYs). Compared with simvastatin, the cost of one LYG with rosuvastatin was €10 834 and the cost of one QALY gained was €36 548 (discount rate 5 % per annum). Corresponding figures for atorvastatin were €31 286/LYG and €105 599/QALY. Conclusions: If the decision makers’ willingness to pay for a QALY gained is around €40 000 there is a high probability ( > 50 % ) that rosuvastatin represents a cost-effective form of therapy in the prevention of CHD in middle-aged men with an average 3.3–6.6 % risk of dying within 10 years from cardiovascular disease. However, the true clinical impact of these results needs confirmation from on-going clinical trials, as the role of rosuvastatin in reducing clinical events is pending, but for simvastatin and atorvastatin established.

Direct costs of warfarin treatment among patients with atrial fibrillation in a Finnish health care setting

ABSTRACT Objective: The main objective was to estimate the mean direct costs of warfarin treatment for atrial fibrillation (AF) patients. Secondly, the costs of initiating warfarin treatment during a 60-day period and the impact of International Normalized Ratio (INR) and co-morbidities on costs were estimated. Design and data: The study was performed as a retrospective cohort study over a 12‐month period in a Finnish communal health care setting. All AF patients aged 65 years or older (n = 250) with warfarin treatment were identified from the database of the health service district of an urban area. Patient specific information related to co-morbidities, INR-control, complications and health care resource use were collected. Cost information was obtained from the Finnish national health care unit cost list. Methods: The effect of treatment balance and other background variables on treatment costs were evaluated using ordinary least squares regression (OLS), log-transformed OLS and generalized linear model (GLM). The mean costs were calculated on the basis of the different models and bias corrected and accelerated (BCa) bootstrap confidence intervals (CIs) were calculated for the mean costs. Results: The best fitting cost model was log-transformed OLS. The costs of warfarin treatment on the basis of the log-transformed model were 589.82 euros (BCa 95% CI: 586.68–591.99) per patient compared to 616.00 euros (BCa 95% CI: 579.98–652.96) obtained with the OLS-model. For the treatment initiation period, the mean costs were 263 euros (BCa 95% CI: 218.90–314.71). Depending on the way that INR-control was defined, the mean costs were 95.27 euros or 166.92 euros higher for patients who were not in the defined INR-balance. Conclusions: The INR-control has a significant impact on the warfarin treatment costs. The choice of model influences the estimated mean costs. In addition, different models identify statistically significant effects between different background variables and costs.

Population-based health-economic evaluation of the secondary prevention of coronary heart disease in Finland

Abstract Objective: To evaluate the cost-effectiveness of generic atorvastatin 20 mg (A20), branded rosuvastatin 10 mg (R10), generic simvastatin 40 mg (S40) and the combination of generic S40 + branded ezetimibe 10 mg (S40 + EZ10) for the secondary prevention of coronary heart disease (CHD) in Finnish patients not meeting the target goal of low-density lipoprotein cholesterol (LDL-C) with S40. Research design and methods: A probabilistic Markov model was employed to evaluate the costs and health outcomes of the different therapies based on the cardiovascular events avoided. The model included Framingham risk equations, Finnish population characteristics, event rates, quality of life estimates, resource use and unit costs. The LDL-C lowering efficacies were gathered from a systematic literature review, based on a search of Medline carried out in June 2008 (no time limit). Main outcome measures: Incremental cost per quality-adjusted life year (QALY) gained and incremental cost per life year gained (LYG). Results: The efficacy (LDL-C decrease) gained from switching S40 to S40 + EZ10 was consistent in the literature review, whereas the LDL-C decrease gained from switching S40 to A20/R10 was uncertain. The incremental cost per QALY gained from switching generic S40 was lowest for S40 + EZ10 (€22,841 [€24,017] and €26,595 [€46,686] for diabetic and non-diabetic men [women], respectively). The respective incremental cost per QALY gained for S40 + EZ10 vs. A20 were €19,738 (€21,405) and €23,596 (€40,087). A20 dominated R10. Based on the cost-effectiveness acceptability frontier with a willingness-to-pay value of €30,000 per QALY gained, the probability of cost-effectiveness for switching generic S40 to S40 + EZ10 was 100% for men and diabetic women. Sensitivity analyses showed that results were robust. Conclusions: In the Finnish secondary prevention population that is not at goal on S40, switching generic S40 to S40 + EZ10 is more cost-effective than switching S40 to generic A20 or R10.

Health economic consequences of reducing salt intake and replacing saturated fat with polyunsaturated fat in the adult Finnish population: estimates based on the FINRISK and FINDIET studies

Background/Objectives:To predict the health economic consequences of modest reductions in the daily intake of salt (−1.0 g per day) and replacement of saturated fat (SFA, −1.0 energy percent (E%)) with polyunsaturated fat (PUFA, +1.0 E%) in the Finnish population aged 30–74 years.Subjects/Methods:A Markov model with dynamic population structure was constructed to present the natural history of cardiovascular diseases (CVDs) based on the most current information about the age- and sex-specific cardiovascular risk factors, dietary habits and nutrient intake. To predict the undiscounted future health economic consequences of the reduction of dietary salt and SFA, the model results were extrapolated for the years 2010–2030 by replacing the baseline population in the year 2007 with the extrapolated populations from the official Finnish statistics. Finnish costs ([euro ]2009, societal perspective) and EQ-5D utilities were obtained from published references.Results:During the next 20 years, a population-wide intervention directed at salt intake and dietary fat quality could potentially lead to 8000–13 000 prevented CVD cases among the Finnish adults compared the situation in year 2007. In addition, the reduced incidence of CVDs could gain 26 000–45 000 quality-adjusted life years and save [euro ]150–225 million over the same time period.Conclusion:A modest reduction of salt and replacement of SFA with PUFA in food products can significantly reduce the burden of CVD in the adult Finnish population. This impact may be even larger in the near future due to the ageing of Finnish population.

Economic evaluation comparing From Home To Operation same day admission and preoperative admission one day prior to the surgery process : a randomized, controlled trial of laparoscopic cholecystectomy

ABSTRACT Objective: A novel preoperative procedure From Home To Operation (FHTO) seeks to combat increasing operation and infection rates. This is the first prospective randomized controlled trial (RCT) comparing the cost-effectiveness and cost-utility of FHTO and conventional ward procedures for standardized Laparoscopic Cholecystectomy (LC). Research design and methods: During 12/2004–7/2005, 47 patients with symptomatic gallstones were randomized to receive LC in the FHTO (28 patients) or in a conventional manner (19 patients) in a Finnish hospital setting. The 15D quality of life tool was administered at the baseline and 1 month after. Main outcome measures: A stochastic approach over a month interval for hospital costs, length of postoperative stay, infection rate and Quality-Adjusted Life Years (QALY) was employed. Results: Baseline group characteristics were similar. The mean health care costs with FHTO (1695 EUR) were significantly lower ( p < 0.001) than in the conventional arm (2234 EUR). The number of patients discharged on the first postoperative day was 27 (96.4%) and 15 (78.9%) with two (7.1%) infections in the FHTO and four (21.1%) in the conventional arm. A difference in QALYs gained (0.0174; p = 0.030) favouring FHTO was observed. According to a cost-effectiveness acceptability curve, the probability of FHTO being cost-effective was 99%. The results were robust to probabilistic sensitivity analyses. Conclusions: FHTO can introduce substantial cost savings and have a positive impact on both clinical measures and quality of life. Studies with larger numbers of patients are needed to assess whether conventional ward procedure can be a source of infections, which can be avoided with FHTO. Clinical Trial Registry: ICJME-qualified registry of the Hospital District of Helsinki and Uusimaa (number 217849).

Bayesian predictors of very poor health related quality of life and mortality in patients with COPD

BackgroundChronic obstructive pulmonary disease (COPD) is associated with increased mortality and poor health-related quality of life (HRQoL) compared with the general population. The objective of this study was to identify clinical characteristics which predict mortality and very poor HRQoL among the COPD population and to develop a Bayesian prediction model.MethodsThe data consisted of 738 patients with COPD who had visited the Pulmonary Clinic of the Helsinki and Turku University Hospitals during 1995–2006. The data set contained 49 potential predictor variables and two outcome variables: survival (dead/alive) and HRQoL measured with a 15D instrument (very poor HRQoL < 0.70 vs. typical HRQoL ≥ 0.70).In the first phase of model validation we randomly divided the material into a training set (n = 538), and a test set (n = 200). This procedure was repeated ten times in random fashion to obtain independently created training sets and corresponding test sets. Modeling was performed by using the training set, and each model was tested by using the corresponding test set, repeated in each training set. In the second phase the final model was created by using the total material and eighteen most predictive variables. The performance of six logistic regressions approaches were shown for comparison purposes.ResultsIn the final model, the following variables were associated with mortality or very poor HRQoL: age at onset, cerebrovascular disease, diabetes, alcohol abuse, cancer, psychiatric disease, body mass index, Forced Expiratory Volume (FEV1) % of predicted, atrial fibrillation, and prolonged QT time in ECG. The prediction accuracy of the model was 77%, sensitivity 0.30, specificity 0.95, positive predictive value 0.68, negative predictive value 0.78, and area under the ROC curve 0.69. While the sensitivity of the model reminded limited, good specificity, moderate accuracy, comparable or better performance in classification and better performance in variable selection and data usage in comparison to the logistic regression approaches, and positive and negative predictive values indicate that the model has potential in predicting mortality and very poor HRQoL in COPD patients.ConclusionWe developed a Bayesian prediction model which is potentially useful in predicting mortality and very poor HRQoL in patients with COPD.