Cost of multiple sclerosis in the Czech Republic: the COMS study.

BACKGROUND: Information about cost of multiple sclerosis (MS) is available from a number of European countries, but no data from the Czech Republic have been published so far. OBJECTIVE: The objective of this study was to establish the cost of MS in the Czech Republic, overall and by level of disease severity. METHODS: Data on demographics, disease history, resource consumption and production losses were collected from 909 patients recruited in 7 MS centres in the Czech Republic. Annual costs were estimated in the societal perspective, using 2007 unit costs. To evaluate the relationship between disability and costs, patients were stratified into those with mild (67%), moderate (27%) and severe (10%) disability using the Expanded Disability Status Scale. RESULTS: Mean total annual costs per patient were €12,272, of which 51% were direct medical costs, 4% direct non-medical costs and 45% indirect costs. The average annual costs in patients with mild, moderate and severe disability amounted to €9905, €14,064 and €22,880, respectively. CONCLUSION: The total costs of MS in the Czech Republic are estimated at €208.6 million per year. Consistent with other studies, the costs increase significantly with the severity of MS.

Costs and outcomes for patients with rheumatoid arthritis treated with biological drugs in Sweden: a model based on registry data.

OBJECTIVE: To design an economic model describing the costs and outcomes for patients treated with tumour necrosis factor alpha (TNFalpha) inhibitors for rheumatoid arthritis (RA) in current clinical practice in Sweden, to be used as a tool to estimate cost-effectiveness of the next generation of treatments. METHODS: The model was constructed as a discrete event simulation (DES) model analysed at patient level. It contains treatment and outcome data for 1903 patients followed in the RA registry for biological drugs in southern Sweden between 1999 and 2007 [the Southern Swedish Arthritis Treatment Group (SSATG) Register]. Resource consumption was based on a survey of 1027 patients in the same region. Costs and quality-adjusted life years (QALYs) are presented for 10(5) years, for patients with the mean characteristics at treatment start in SSATG [Health Assessment Questionnaire (HAQ) score 1.33, disease duration 12.1 years, age 55 years], but also for patients with more or less severe disease. Cost and outcomes (QALYs) are discounted with 3%. RESULTS: The 10-year costs in the base case amount to USD 336,000 (SD USD 64,000) or EUR 223 000, with a total of 4.4 QALYs. Over 5 years, the costs amount to USD 208,000 or EUR 138,000 and QALYs to 2.5. The results were most sensitive to HAQ level at treatment start, but also to underlying disease progression, age, and disease duration. Starting treatment at a lower HAQ level (0.85) reduces costs by 10% and increase QALYs by 20%. CONCLUSION: This analysis is based on the longest available follow-up for patients treated with TNFalpha inhibitors and provides an opportunity to explore treatment strategies when new therapies become available using actual clinical practice data.

The long-term cost of multiple sclerosis in France and potential changes with disease-modifying interventions.

OBJECTIVE: To evaluate the long-term costs and quality of life (QoL) with and without disease-modifying treatments (DMTs) of patients with multiple sclerosis (MS). METHODS: Data on resource consumption, productivity losses, QoL (utility), and fatigue were collected from 1355 patients registered with a patient association and descriptive analyses was performed.A Markov model was developed to estimate costs and utility over 20 years using the survey data. Disease progression without DMTs was taken from an epidemiological cohort in France (EDMUS cohort, LYON). Progression under DMTs was estimated from the Stockholm MS registry. Results are presented as cost per quality-adjusted life-years (QALYs), from the societal perspective, in EUR2007, discounted at 3%. RESULTS: Mean Expanded Disability Status Scale (EDSS) was 4.4 and mean total annual costs per patient were EUR44,400, of which 47% were productivity losses and 11% informal care. Public payers cover an estimated 48% of costs. Mean utility was 0.52, and the loss compared with the normal population was estimated at 0.28. Costs and utility ranged from EUR16,000 and 0.79 at EDSS 1 to EUR76,000 and 0.11 at EDSS 8-9.Over 20 years, costs were estimated at EUR429,000 and QALYs at 8.96 for patients without DMTs and at EUR433,207 and 9.24 QALYs if all patients were starting treated with DMTs at EDSS 1-3. CONCLUSION: Although the data for this analysis come from different sources, the results indicate that the cost increase with DMTs is moderate.

Modeling the cost-effectiveness of a new treatment for MS (natalizumab) compared with current standard practice in Sweden.

OBJECTIVE: To estimate the cost-effectiveness of a new treatment (natalizumab) for multiple sclerosis (MS) compared with current standard therapy with disease-modifying drugs (DMDs) in Sweden. METHODS: A Markov model was constructed to illustrate disease progression based on functional disability (the Expanded Disability Status Scale (EDSS)). The effectiveness of natalizumab was based on a 2-year clinical trial in 942 patients (AFFIRM). The effectiveness of current DMDs was estimated from a matched sample of 512 patients in the Stockholm MS registry. Patients withdrawing from treatment were assumed to follow the disease course of 824 patients with relapsing-remitting disease at onset in the Ontario natural history cohort. Costs and utilities are based on a recent observational study in 1339 patients. All data sets were available at the patient level. Main results are presented from the societal perspective, over a 20-year time frame, in 2005 Euros (euro1 = 9.25 SEK). RESULTS: In the base case, treatment with natalizumab was less expensive and more effective than treatment with current DMDs. When only healthcare costs were considered, the cost per quality-adjusted life year gained with natalizumab was euro38 145. Results are sensitive only to the time horizon of the analysis and assumptions about effectiveness of natalizumab beyond the trial. CONCLUSIONS: This cost-effectiveness analysis used registry data, cohort and observational studies to extrapolate the efficacy findings of natalizumab from the AFFIRM clinical trial to measure effectiveness in clinical practice. The analysis results suggest that for the population considered, natalizumab provides an additional health benefit at a similar cost to current DMDs from a societal perspective.

The costs of treating glaucoma with combinations of topical drugs in Spain.

PURPOSE: This study describes the treatment in ordinary clinical practice in Spain of patients with glaucoma with a two-drug combination therapy. The authors present the treatment outcome as endof-period intraocular pressure (IOP) and the calculated direct medical costs over a 2-year period. METHODS: Data were extracted retrospectively from patient charts recording the use of all medical resources related to glaucoma. Costs were estimated using unit costs from public sources (2005). Descriptive cost analysis according to combination treatment at baseline was performed. RESULTS: The study included 216 patients from 21 centers. Around half of the patients were started on a beta-blocker/prostaglandin analogue combination, while the rest received various other combinations containing either an alpha2-agonist or a carbonic anhydrase inhibitor. Across the seven groups considered, there was a statistically significant difference in the costs of the least and the two most costly groups, while the confidence intervals were overlapping in all other pairwise comparisons. The least costly drug combination was brimonidine/timolol. Assessing IOP at the end of follow-up, all the groups were equally effective (overlapping confidence intervals). In a multivariate regression analysis, the drug combination did not have an independent, significant impact on total direct medical costs, drug costs, or end-of-period IOP. Significant determinants of these variables were surgical interventions and one or more changes of drug combination during the follow-up. CONCLUSIONS: Costs are determined by the response to treatment. Inadequate response triggers treatment changes and sometimes eventually surgical interventions, thereby increasing costs significantly.

The cost-effectiveness of infliximab in the treatment of ankylosing spondylitis in Spain. Comparison of clinical trial and clinical practice data.

OBJECTIVE: To estimate the cost-effectiveness of treating ankylosing spondylitis (AS) with infliximab (Remicade) in Spain for up to 40 years. METHODS: A previously published disease model was adapted to the Spanish setting using resource consumption from a cross-sectional burden of an illness study in 601 patients in Spain. Cost-effectiveness estimates were based on a placebo-controlled clinical trial as well as an open clinical study in Spain. In the model, patients with insufficient response to treatment at 12 weeks [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) <4 or > or =50% reduction] discontinue treatment. The results are presented in 2005 euros, from societal and health-care payer perspectives. RESULTS: In the societal perspective, infliximab treatment dominates standard treatment in both analyses. In the perspective of the health-care system, with the assumption that, over the long term, functional ability of patients on treatment would decline at half the natural rate, the cost per quality-adjusted life year (QALY) gained was estimated at EUR 22 519 (double-blind trial) and EUR 8866 (open study). Assuming that patients' function on treatment remains stable, the cost-effectiveness ratios are EUR 15 157 and EUR 5307, respectively. Under the most conservative assumption (no effect of treatment on progression), the ratios are EUR 31 721 and EUR 13 659, respectively. In addition, the results are sensitive to the time horizon and discontinuation rates. CONCLUSIONS: Our results indicate that infliximab therapy for patients with active AS should be cost-effective both in the societal perspective (dominating) and in the perspective of the health-care system (ranges from EUR 5300 to EUR 32 000 per QALY) in Spain.

The burden of rheumatoid arthritis and access to treatment: uptake of new therapies.

This paper presents data on international differences in use of TNF inhibitors. It is part of a study on burden and cost of RA, access to new therapies and the role of HTA in determining access and cost-effectiveness. United States has the fastest most extensive use of the new drugs, about three times the average in the western European countries and Canada. Eastern and central European countries as well as Australia, South Africa and Turkey lag far behind. However, some smaller European countries, most notably Norway and Sweden have use of the new drugs not far behind the United States. While the income level of the country, and thus the health care expenditures per capita is a major factor for determining use in low and middle income countries, there are still considerable differences among countries with similar high total health care expenditures. Differences in prices are considerable between the US and Europe due to the changes in exchange rates between the US dollar and the Euro, but high and low use is not systematically related to differences in price.

The burden of rheumatoid arthritis and access to treatment: outcome and cost-utility of treatments.

Within the series of articles investigating the burden of rheumatoid arthritis (RA), this paper reviews the methods used for economic assessment of the RA treatments by HTA agencies and other bodies involved in cost-effectiveness analysis and the current status of the field. The overall methods, as well as the challenges, of cost-effectiveness analysis in RA are common to all chronic progressive diseases where much of the treatment benefit is delayed, while costs occur immediately. Also, as in all disabling diseases, much of the costs occur outside the health-care system, due to the rapid loss of work capacity and the need for informal care in the later stages of the disease. Thus, it is essential to adopt a long-term view and consider costs from the perspective of society, rather than the health-care service, to increase the relevance of the results for policy making.

The burden of rheumatoid arthritis and access to treatment: determinants of access.

As part of the study "The Burden of Rheumatoid Arthritis (RA) and Patient Access to Treatment", this paper reviews the impact on access to RA drugs of the approval processes, pricing and funding decisions and times to market (access) in different countries. In addition, an overview of health technology assessments (HTA) and the economic literature related to RA treatments is provided. The time from approval to market access ranged from immediate to over 500 days in the countries included in the study. A total of 55 HTA reports were identified, 40 of them in the period between 2002 and 2006; 29 were performed by European HTA agencies, 14 in Canada and 7 in the United States. A total of 239 economic evaluations related to RA were identified in a specialized health economic database (HEED).

The burden of rheumatoid arthritis and access to treatment: health burden and costs.

As part of the study "The burden of rheumatoid arthritis and patient access to treatment", this paper reviews evidence on the health burden of rheumatoid arthritis (RA) in terms of morbidity (DALYs), mortality (% of deaths attributable to RA) and quality of life (utility and loss of QALYs), as well as the economic impact on society. Based on available literature on the prevalence and the cost of RA, combined with economic indicators, the annual cost per patient as well as the total national cost is estimated for Europe and North America (Canada and the United States), as well as Australia, Turkey, the Russian Federation and South Africa. Total costs to society were estimated at 45.3 billion in Europe and at 41.6 billion in the United States. Utility scores were found to be amongst the lowest compared to other diseases.

Estimation of the cost of MS in Europe: extrapolations from a multinational cost study.

The present study aims at estimating the total cost of MS in Europe based on actual cost data from nine countries and published epidemiological evidence. The epidemiological data are reported as 12 months prevalence estimates and cost data calculated as annual cost per patient at given levels of disease severity. Cost data are extrapolated to the rest of Europe based on a model, using economic indexes adjusting for price level differences in different sectors between countries. The aggregated annual cost estimates are presented in Euro for 2005. In 28 European countries with a population of 466 million, an estimated 380 000 individuals are affected by MS. The total annual cost of MS in Europe is estimated at 12.5 billion in year 2005, corresponding to a cost of 27 per European inhabitant. Direct costs represent slightly more than half of the total cost (6.0 billion). Informal care is estimated at 3.2 billion, and indirect costs due to morbidity at 3.2 billion. Thus, the largest component of costs is found outside the formal health care sector. Although our model appears to predict costs reasonably well, when comparing to previous national studies not included in the estimates, there are considerable uncertainties when extrapolating cost data across countries even within Europe. These weaknesses can only be overcome by collecting primary data.

Rheumatoid arthritis: what does it cost and what factors are driving those costs? Results of a survey in a community-derived population in Malmö, Sweden.

OBJECTIVE: We sought to investigate the cost of living with rheumatoid arthritis (RA) and evaluate the influence of both demographics and specific disease characteristics on these costs. METHODS: We used a population-based questionnaire to survey 895 patients living in the city of Malmö, Sweden, during 2002. Data were obtained on direct resource consumption, investments, informal care and work capacity, as well as utility, function and patients' assessment of disease severity and pain. RESULTS: The survey was completed by 613 patients (68%). Their mean age was 66 years, 74% were female and the mean duration of disease was 16.7 years. The total mean annual cost per patient was 108,370 SEK (12,020 EUR). Direct costs represented 41% of that amount and were predominantly for drugs [14% of the participants were receiving treatment with tumour necrosis factor (TNF) blockers], community services and hospitalisation. Function measured with the Health Assessment Questionnaire (HAQ) was the main statistical predictor for all types of costs except sick leave, which was most strongly associated with patients' perception of global health. CONCLUSION: This is the first study in Sweden to include all costs incurred by a group representative of RA in the community. In comparison with previous studies, total costs had increased by more than 40%. Furthermore, direct costs were higher and constituted a great proportion of total costs because of more intensive treatments (i.e. the use of TNF blockers). Future comparisons will enable health economic evaluations on a community level.

Costs and quality of life of patients with multiple sclerosis in Europe.

OBJECTIVE: To assess overall resource consumption, work capacity and quality of life of patients with multiple sclerosis in nine European countries. METHODS: Information on resource consumption related to multiple sclerosis, informal care by relatives, productivity losses and overall quality of life (utility) was collected with a standardised pre-tested questionnaire from 13,186 patients enrolled in national multiple sclerosis societies or followed up in neurology clinics. Information on disease included disease duration, self-assessed disease severity and relapses. Mean annual costs per patient (Euro, 2005) were estimated from the societal perspective. RESULTS: The mean age ranged from 45.1 to 53.4 years, and all levels of disease severity were represented. Between 16% and 29% of patients reported experiencing a relapse in the 3 months preceding data collection. The proportion of patients in early retirement because of multiple sclerosis ranged from 33% to 45%. The use of direct medical resources (eg, hospitalisation, consultations and drugs) varied considerably across countries, whereas the use of non-medical resources (eg, walking sticks, wheel chairs, modifications to house and car) and services (eg, home care and transportation) was comparable. Informal care use was highly correlated with disease severity, but was further influenced by healthcare systems and family structure. All types of costs increased with worsening disease. The total mean annual costs per patient (adjusted for gross domestic product purchasing power) were estimated at Euro 18,000 for mild disease (Expanded Disability Status Scale (EDSS) <4.0), Euro 36,500 for moderate disease (EDSS 4.0-6.5) and Euro 62,000 for severe disease (EDSS >7.0). Utility was similar across countries at around 0.70 for a patient with an EDSS of 2.0 and around 0.45 for a patient with an EDSS of 6.5. Intangible costs were estimated at around Euro 13,000 per patient.

Health economic issues in MS.

The objectives of MS treatment are to avoid temporary disability due to relapses and to delay progression to permanent disability. There have been intense debates about whether new and costly MS treatments represent efficient use of resources, and which patients should be treated. Cost-effectiveness analysis attempts to estimate the trade-offs involved and to provide information that will assist the decision-making process. In chronic-progressive diseases, health gains and potential associated economic benefits are often most evident in the long term. Consequently, the potential impact of new treatments must be estimated, using models that project available knowledge into the future. These models can also explore scenarios that provide best value for money (e.g. by defining subgroups or criteria when treatment should be stopped). The different findings obtained by various cost-effectiveness studies of new MS treatments can be explained by the variations in methodological approaches, patient definitions and datasets used. The key is to communicate such differences transparently.

Health economic issues in rheumatoid arthritis.

The objectives of treatment in rheumatoid arthritis (RA) are to reduce temporary symptoms due to inflammatory activity and, more importantly, to preserve function. The introduction of potent disease-modifying anti-rheumatic drugs (DMARDs) in recent years has increased the opportunities for effective treatment. However, these treatments come at a substantially higher cost than traditional DMARDs and therefore compete with other essential interventions for limited resources. They have triggered a debate on whether they represent an efficient use of resources, which patients should be treated, when, and for how long. Cost-effectiveness analysis attempts to estimate the trade-offs involved in these decisions and to provide information that can help in making them. However, in chronic progressive diseases, health gains and any potential associated economic benefits are often most evident in the long-term. As a consequence, the impact of new treatments has to be estimated using models that can project available knowledge, such as results from clinical trials or short-term follow-up studies in clinical practice, into the future. These models also allow scenarios to be explored that provide the best value for money, for example by defining subgroups for which treatment is most effective, or criteria that define when treatment should be stopped. Economic evaluation in RA has a long tradition, with the first study performed about 20 years ago. However, with the recent drug introductions, the field has witnessed an explosion of economic studies. Modelling techniques have become more sophisticated to overcome concerns about their validity. At the same time, they may appear less transparent, making it difficult for non-specialists to understand the details. This article, rather than reviewing all published models and comparing them, attempts to illustrate the inputs required for such studies, and the influence that different approaches and datasets can have on the results.

Modelling the effect of function and disease activity on costs and quality of life in rheumatoid arthritis.

OBJECTIVE: When treatments with the potential to change the natural history of a disease are introduced, their longer-term effect on costs and quality of life (utility) has to be estimated using economic models. However, to remain useful tools, models must be updated when new information becomes available. Our earlier models in rheumatoid arthritis (RA) have been based on functional status, but it has recently been shown that disease activity might have an independent effect on utility. The objective of this study was to improve the model by incorporating the effect of a subjective measure of disease severity and activity (global VAS). METHODS: A Markov model was constructed with five states according to functional status (HAQ), and each state was subdivided according to the VAS (<40 and >40). Disease development (transition probabilities between the states) was taken from a longitudinal cohort study of patients with early RA in Sweden. A recent population-based survey of 616 patients with RA provided data on costs and utilities. The model incorporates the full distribution of costs and utilities from the survey, and long-term projections are made using Monte Carlo simulation. RESULTS: The global VAS had a highly significant effect on utilities independently of HAQ. For resource consumption, only HAQ was a significant predictor, with the exception of sick leave, which was correlated with the VAS but not with HAQ. Using the cohort distribution from the longitudinal study, expected mean costs per patient over 10 yr were 106 034 euros (s.d. 5091 euros) (1 euro = SEK 9.20) and the expected number of quality-adjusted life years (QALYs) was 5.08 (s.d. 0.09). Patients starting at HAQ <0.6 but with consistently high VAS scores would have expected costs of 102 830 euros and 4.96 QALYs, while patients with low VAS scores would have costs of 81 603 euros and 6.01 QALYs. CONCLUSION: Our new model incorporates for the first time the effect of a subjective measure of disease severity and activity on both costs and utility, making it a sensitive tool to estimate the cost-effectiveness of disease-modifying treatments. New data on resource consumption indicate a shift to higher direct costs, particularly in early disease, and lower indirect costs in more advanced disease. The large size of the data sets used in this model reduces the uncertainty and makes estimates very stable.

Cost effectiveness of etanercept (Enbrel) in combination with methotrexate in the treatment of active rheumatoid arthritis based on the TEMPO trial.

OBJECTIVE: To estimate the cost effectiveness of combination treatment with etanercept plus methotrexate in comparison with monotherapies in patients with active rheumatoid arthritis (RA) using a new model that incorporates both functional status and disease activity. METHODS: Effectiveness data were based on a 2 year trial in 682 patients with active RA (TEMPO). Data on resource consumption and utility related to function and disease activity were obtained from a survey of 616 patients in Sweden. A Markov model was constructed with five states according to functional status (Health Assessment Questionnaire (HAQ)) subdivided into high and low disease activity. The cost for each quality adjusted life year (QALY) gained was estimated by Monte Carlo simulation. RESULTS: Disease activity had a highly significant effect on utilities, independently of HAQ. For resource consumption, only HAQ was a significant predictor, with the exception of sick leave. Compared with methotrexate alone, etanercept plus methotrexate over 2 years increased total costs by 14,221 euros and led to a QALY gain of 0.38. When treatment was continued for 10 years, incremental costs were 42,148 euros for a QALY gain of 0.91. The cost per QALY gained was 37,331 euros and 46,494 euros, respectively. The probability that the cost effectiveness ratio is below a threshold of 50,000 euros/QALY is 88%. CONCLUSION: Incorporating the influence of disease activity into this new model allows better assessment of the effects of anti-tumour necrosis factor treatment on patients' general wellbeing. In this analysis, the cost per QALY gained with combination treatment with etanercept plus methotrexate compared with methotrexate alone falls within the acceptable range.