Taru Hallinen

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.

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.

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.

Price-cost margin in the pharmaceutical industry

This contribution estimates the price-cost margin in the Finnish pharmaceutical industry. The estimation is based on the method developed by Hall who shows that under constant returns to scale total factor productivity growth depends on the growth of output-capital ratio if the market is imperfectly competitive. Measurement of the price-cost margin is based on this theoretical result. We utilize data on the Finnish pharmaceutical industry. The data cover the years 1975–1999 and include information on output, labor hours, and capital stock. The results show that the estimated price-cost margin is in the range 0.59–0.67, which is close to the estimates obtained in the United States market.

Warfarin treatment among Finnish patients with atrial fibrillation: retrospective registry study based on primary healthcare data

Objective To assess the frequency of warfarin use, the achieved international normalised ratio (INR) balance among warfarin users and the primary healthcare outpatient costs of patients with atrial fibrillation (AF). Design Retrospective, non-interventional registry study. Setting Primary healthcare. Participants All patients with AF (n=2746) treated in one Finnish health centre between October 2010 and March 2012. Methods Data on healthcare resource use, warfarin use, individually defined target INR range and INR test results were collected from the primary healthcare database for patients with AF diagnosis. The analysed dataset consisted of a 1-year follow-up. Warfarin treatment balance was estimated with the proportion of time spent in the therapeutic INR range (TTR). The cost of used healthcare resources was valued separately with national and service provider unit costs to estimate the total outpatient treatment costs. The factors potentially impacting the treatment costs were assessed with a generalised linear regression model. Results Approximately 50% of the patients with AF with CHADS-VASc ≥1 used warfarin. The average TTR was 65.2% but increased to 74.5% among patients using warfarin continuously (ie, without gaps exceeding 56 days between successive INR tests) during follow-up. One-third of the patients had a TTR of below 60%. The average outpatient costs in the patient cohort were €314.44 with the national unit costs and €560.26 with the service provider unit costs. The costs among warfarin users were, on average, €524.11 or €939.54 higher compared with the costs among non-users, depending on the used unit costs. A higher TTR was associated with lower outpatient costs. Conclusions The patients in the study centre using warfarin were, on average, well controlled on warfarin, yet one-third of patients had a TTR of below 60%.

Administration costs of intravenous biologic drugs for rheumatoid arthritis.

BackgroundCost-effectiveness studies explicitly reporting infusion times, drug-specific administration costs for infusions or real-payer intravenous drug cost are few in number. Yet, administration costs for infusions are needed in the health economic evaluations assessing intravenously-administered drugs.ObjectivesTo estimate the drug-specific administration and total cost of biologic intravenous rheumatoid arthritis (RA) drugs in the adult population and to compare the obtained costs with published cost estimates.MethodsCost price data for the infusions and drugs were systematically collected from the 2011 Finnish price lists. All Finnish hospitals with available price lists were included. Drug administration and total costs (administration cost + drug price) per infusion were analysed separately from the public health care payer’s perspective. Further adjustments for drug brand, dose, and hospital type were done using regression methods in order to improve the comparability between drugs. Annual expected drug administration and total costs were estimated. A literature search not limited to RA was performed to obtain the per infusion administration cost estimates used in publications. The published costs were converted to Finnish values using base-year purchasing power parities and indexing to the year 2011.ResultsInformation from 19 (95%) health districts was obtained (107 analysable prices out of 176 observations). The average drug administration cost for infliximab, rituximab, abatacept, and tocilizumab infusion in RA were €355.91; €561.21; €334.00; and €293.96, respectively. The regression-adjusted (dose, hospital type; using semi-log ordinary least squares) mean administration costs for infliximab and rituximab infusions in RA were €289.12 (95% CI €222.61–375.48) and €542.28 (95% CI €307.23–957.09). The respective expected annual drug administration costs were €2312.96 for infliximab during the first year, €1879.28 for infliximab during the forthcoming years, and €1843.75 for rituximab. The obtained average administration costs per infusion were higher (1.8–3.3 times depending on the drug) than the previously published purchasing power adjusted and indexed average administration costs for infusions in RA.ConclusionsThe administration costs of RA infusions vary between drugs, and more effort should be made to find realistic drug-specific estimates for cost-effectiveness evaluations. The frequent assumption of intravenous drug administration costs equalling outpatient visit cost can underestimate the costs.

The Impact of the Pharmaceutical Pricing System on Cost-Effectiveness Results: Finnish Analysis

In Finland, the drug retail prices are determined with a regressive pharmaceutical pricing scheme (PPS) that leads to higher absolute sales margins for products with higher wholesale prices. At the same time low-priced products are sold at prices below the true costs of drug delivery. Despite these characteristics retail prices are used to represent all drug costs in health economic evaluations that are required before societal reimbursement of new drugs can be granted. We assessed the impact of PPS induced cost differences on the results of cost-utility analyses in hypothetical examples. The examples show that the Finnish PPS worsens the ICERs obtained for more expensive pharmaceuticals. The Finnish PPS is problematic when the aim is to provide Finnish patients with optimal, cost-effective treatments. In its current form, the PPS discourages innovation and comparability of results with other settings, and may prevent reimbursement of otherwise cost-effective treatments.

Cost-utility analysis of vortioxetine versus agomelatine, bupropion SR, sertraline and venlafaxine XR after treatment switch in major depressive disorder in Finland

ABSTRACT Background: To assess the cost-utility of vortioxetine versus relevant comparators (agomelatine, bupropion SR, sertraline, and venlafaxine XR) in the finnish setting in major depressive disorder (MDD) patients with inadequate response to selective serotonin- /serotonin–norepinephrine reuptake inhibitors. Methods: A one-year analysis was conducted using a decision tree with a Markov state transition component. The health states were remission, relapse and recovery. A Finnish healthcare payer perspective was adopted. Results: Vortioxetine was less costly and more effective versus all comparators in both direct and societal perspectives. Vortioxetine reduced the average annual direct costs by 4% versus venlafaxine XR and 8% versus sertraline. The greater efficacy associated with vortioxetine was translated into a higher percentage of patients in remission and recovery. The model was most sensitive to changes in remission rates at 8 weeks. Conclusion: This cost-utility analysis showed vortioxetine to be a good alternative for MDD patients switching therapy in Finland.