Janne Martikainen

Treatment of follicular non-Hodgkin's lymphoma with or without rituximab: cost-effectiveness and value of information based on a 5-year follow-up

Background: Rituximab induction together with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and rituximab maintenance (RCHOP-R) resulted to significant progression-free survival (PFS) benefit in comparison to RCHOP in the EORTC20981 trial of relapsed/refractory follicular non-Hodgkins lymphoma (FL). However, the overall survival (OS) difference between RCHOP-R and RCHOP was insignificant. This study evaluated the cost-effectiveness of RCHOP, RCHOP-R, and CHOP in the treatment of relapsed/refractory FL. Design: A lifetime Markov modeling based on the 5-year EORTC20981 survivals (Weibull regressions) was carried out from the public health care payer perspective. Finnish costs (drug, routine, adverse event, and relapse management) were employed. The main outcomes were incremental cost (€2008) per quality-adjusted life-year (QALY), progression-free year (PFY), and life-years gained (LYG). Analyses included cost-effectiveness acceptability frontier and multinomial expected value of perfect information (mEVPI). Results: RCHOP-R resulted to OS (PFS) benefit compared with RCHOP and CHOP: 6 (10) and 17 (25) months, respectively. The incremental costs per QALY gained/LYG/PFY gained were €18 147/€16 380/€10 416 for RCHOP-R versus RCHOP (mEVPI €5196); €14 360/€13 041/€8976 for RCHOP-R versus CHOP (mEVPI €1986); and €12 123/€11 049/€8004 for RCHOP versus CHOP (mEVPI €1,240). RCHOP-R was the optimal option when the willingness to pay per QALY gained exceeded €18 399. Conclusion: RCHOP-R is a potentially cost-effective treatment option for the FL.

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.

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.

Economic evaluation of temozolomide in the treatment of recurrent glioblastoma multiforme

AbstractBackground: Temozolomide (TMZ) is an oral alkylating agent with demonstrated efficacy as therapy for glioblastoma multiforme (GBM) and anaplastic astrocytoma. TMZ has widely replaced the procarbazine, lomustine plus vincristine (PCV) combination for the treatment of malignant brain tumours as a result of its oral administration and favourable toxicity profile. Objectives: This study had three related aims. First, the cost effectiveness of TMZ (from the Finnish healthcare payer perspective) was compared with PCV in patients with GBM that had relapsed after primary treatment with surgery and radiotherapy. Second, the probability that TMZ is cost effective, compared with PCV, was estimated at different societal willingness-to-pay levels. Third, the value of new information for reducing the uncertainty related to the choice of treatment between TMZ and PCV was evaluated. Methods: The cost effectiveness of TMZ and PCV was evaluated using a decision-modelling approach. Incremental cost-effectiveness ratios (ICERs) for cost per gained life-month, progression-free life-month and QALY were calculated. Various information sources were used to acquire parameter values for the model. The efficacy information of both treatments was derived from the medical literature, quality-of-life (QOL) estimates were gathered from Finnish neurooncologists using visual analogue scale methods, and data on the use of healthcare resources were collected from hospital databases. The exact prices for resource use were gained from the list of Finnish health service unit costs (year 2001 prices). The model was analysed using second-order Monte Carlo simulation. The value of new information on reducing uncertainty was analysed using the expected value of perfect information (EVPI) approach. Results: According to the derived ICERs, 1 extra life-month gained with TMZ costs €2367, 1 extra progression-free life-month costs €2165, and 1 extra QALY costs €32 471, compared with PCV, in the treatment of GBM. The probability of TMZ being the most cost-effective choice of treatment was >60% for all levels of willingness to pay >€5000 per gained life-month. The respective probabilities were >75% for all levels of willingness to pay >€10 000 per gained progressionfree life-month and about 85% for all levels of willingness to pay >€20 000 per gained quality-adjusted life-month. According to EVPI analysis, future research would potentially be cost effective if the costs of research were €4.1 million (maximum). Conclusions: On the basis of this Finnish analysis, TMZ has a high probability of being more cost effective than PCV for patients with GBM. The addition of QOL aspects to the prolonging of survival increases the probability further.

Short-course adjuvant trastuzumab therapy in early stage breast cancer in Finland: Cost-effectiveness and value of information analysis based on the 5-year follow-up results of the FinHer Trial

Abstract Background. Trastuzumab is a standard treatment of HER2-positive early breast cancer in many countries, and it is usually given as a one year adjuvant treatment. However, its cost-effectiveness has not been assessed in Finland. The Finland Herceptin (FinHer) trial has compared a shorter 9-week treatment protocol against no trastuzumab with promising results. The aim of this study was to assess the potential cost-effectiveness of the 9-week treatment based on the recently published five-year follow-up results of the FinHer trial. Methods. An evaluation model of breast cancer treatment was constructed using fitted survival estimates and a long-term Markov model. The cost-effectiveness of 9-week adjuvant treatment was assessed in a Finnish setting, compared to treatment without trastuzumab. The analysis was performed from a societal perspective, and a 3% discount rate was applied for future costs and outcomes. Value of information analysis was performed to estimate the potential value of further research. Results. According to the probabilistic analysis, the incremental cost-effectiveness ratio was €12 000 per quality adjusted life year (QALY), and €9300 per life year gained (LYG), when comparing adjuvant trastuzumab therapy to standard treatment without trastuzumab. The modelled incremental outcomes for trastuzumab treatment were 0.66 QALY and 0.85 LYG for a lifetime perspective. Value of information analysis showed that additional research on treatment effects would be most valuable for reducing uncertainty in the adoption decision. Conclusions. Adjuvant 9-week trastuzumab is likely to be a cost-effective treatment in the Finnish setting. Results from an ongoing trial comparing adjuvant 9-week treatment with the 12-month treatment will play a key role in addressing the uncertainty related to the treatment effect and potential cost-effectiveness of these two treatment protocols.

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.

Budget impact analysis of trastuzumab in early breast cancer: A hospital district perspective

OBJECTIVES Adjuvant trastuzumab is widely used in HER2-positive (HER2+) early breast cancer, and despite its cost-effectiveness, it causes substantial costs for health care. The purpose of the study was to develop a tool for estimating the budget impact of new cancer treatments. With this tool, we were able to estimate the budget impact of adjuvant trastuzumab, as well as the probability of staying within a given budget constraint. METHODS The created model-based evaluation tool was used to explore the budget impact of trastuzumab in early breast cancer in a single Finnish hospital district with 250,000 inhabitants. The used model took into account the number of patients, HER2+ prevalence, length and cost of treatment, and the effectiveness of the therapy. Probabilistic sensitivity analysis and alternative case scenarios were performed to ensure the robustness of the results. RESULTS Introduction of adjuvant trastuzumab caused substantial costs for a relatively small hospital district. In base-case analysis the 4-year net budget impact was 1.3 million euro. The trastuzumab acquisition costs were partially offset by the reduction in costs associated with the treatment of cancer recurrence and metastatic disease. CONCLUSIONS Budget impact analyses provide important information about the overall economic impact of new treatments, and thus offer complementary information to cost-effectiveness analyses. Inclusion of treatment outcomes and probabilistic sensitivity analysis provides more realistic estimates of the net budget impact. The length of trastuzumab treatment has a strong effect on the budget impact.

Early psychosocial intervention does not delay institutionalization in persons with mild Alzheimer disease and has impact on neither disease progression nor caregivers' well-being: ALSOVA 3-year follow-up.

Early diagnosis, initiation of Alzheimers disease (AD) therapy and programs that support care of persons with AD at home are recommended. The objective of this study was to assess the effect of early psychosocial intervention on delaying the institutionalization of persons with AD. We also assessed the influence of intervention on AD progression, behavioral symptoms, and health‐related quality of life (HRQoL) in persons with AD and caregivers.