Economic evaluation of celecoxib, a new cyclo-oxygenase 2 specific inhibitor, in Switzerland.

OBJECTIVE: The aim of this study was to predict the cost effectiveness of celecoxib, a cyclo-oxygenase 2 (COX-2) specific inhibitor, in the treatment of arthritis patients in Switzerland. METHODS: We applied a decision analytical model to compare the effects of 6 months' treatment with the following: (i) celecoxib; (ii) nonsteroidal anti-inflammatory drug (NSAID) alone; NSAID protected with (iii) proton pump inhibitor (PPI), (iv) histamine H2 receptor antagonist (H2RA), or (v) misoprostol; and (vi) diclofenac/misoprostol. Treatment costs included drug acquisition and the management of gastrointestinal (GI) adverse effects, classified as GI discomfort, symptomatic ulcer, anaemia and serious GI events (requiring hospitalisation). Probabilities were derived from celecoxib clinical trials and the literature. Drug utilisation patterns and treatment costs reflecting Swiss practice were obtained from local sources. Analysis was from the public health insurers' perspective. A range of sensitivity analyses was performed. RESULTS: For the base case of patients at typical risk (0.56% per 6 months) of serious GI events, the total expected costs of 6 months' treatment were as follows: celecoxib 435 Swiss francs (SwF); NSAID alone SwF510; diclofenac/misoprostol SwF522; and other protected NSAID regimens between SwF1034 and SwF1415. Celecoxib remained the lowest costing treatment over all categories of GI risk. Celecoxib generated 115 expected adverse events per 1000 patients per 6 months, followed by NSAID + PPI (119), NSAID + H2RA (154), NSAID + misoprostol (202), diclofenac/misoprostol (203), and NSAID alone (220), again for the base case. The cost per adverse event averted for celecoxib compared with NSAIDs alone was estimated in a stochastic version of the model using Monte Carlo simulation. In 95% of 500 iterations, celecoxib was predicted to save both costs and adverse events, thus dominating NSAIDs alone; the maximum cost per adverse event averted was SwF440. CONCLUSIONS: Celecoxib is predicted to be the most cost effective of the treatments considered for managing arthritis patients in Switzerland. A policy of switching patients from NSAIDs to celecoxib is predicted to be cost saving for public health insurers, while reducing the burden of iatrogenic GI side effects. Greater cost savings would be realised when patients are switched from NSAIDs used with gastroprotective agents. Models such as this can provide a useful but simplified view of treatment outcomes and predicted results require prospective validation in clinical practice.

The burden of arthritis and nonsteroidal anti-inflammatory treatment. A European literature review.

The purpose of this literature review is to summarise data available from publications describing the burden of osteoarthritis and rheumatoid arthritis in Europe, and to highlight gaps in the literature. On the basis of extensive literature research, the epidemiology of arthritis, its treatment costs, and iatrogenic costs related to nonsteroidal anti-inflammatory drug (NSAID) treatments are described, differentiating results by country. The review shows that, as well as having a significant impact on healthcare budgets, arthritis also affects patients and caregivers. For those countries where data were available, indirect costs were found to be of comparable magnitude to direct costs. Additionally, it was found that the iatrogenic costs related to the treatment of NSAID-induced adverse events are a significant component of the total costs of arthritis. The number of publications on the burden of arthritis in Europe is rather small in comparison with what is available for the US. Comparison of national results shows wide variations between countries, which may be partly due to discrepancies in the methodology applied to estimate the burden of arthritis, the cost items included in the analysis, and the data sources used to gather cost information. Additionally, comparing the burden of arthritis by country across Europe is difficult because of the variety of ways in which results are presented, e.g. on a per-patient basis, or for the whole population. To better understand the burden of illness of arthritis in Europe, not only is more research required, but the methodology to be applied in burden-of-illness analyses must also be standardised.

An economic model for determining the costs and consequences of using various treatment alternatives for the management of arthritis in Canada.

OBJECTIVE: To construct a decision analytical model to compare the costs and clinical consequences of treating patients with celecoxib or various nonsteroidal anti-inflammatory drug (NSAID)/gastrointestinal (GI) co-therapy regimens for the management of osteoarthritis and rheumatoid arthritis. The model quantified the number of patients expected to experience any GI complication commonly associated with NSAID therapy. DESIGN: Resource use for the treatment of each GI complication in the model was estimated after consulting Canadian experts. Standard unit costs from Ontario were applied to resources to calculate the cost of each complication. MAIN OUTCOME MEASURES AND RESULTS: The model revealed that the NSAID-alone regimen was associated with the lowest cost [$262 Canadian dollars ($Can) per patient per 6 months] followed by the celecoxib regimen ($Can273), diclofenac/misoprostol ($Can365), NSAID + histamine H2 receptor antagonist ($Can413), NSAID + misoprostol ($Can421), and NSAID + proton pump inhibitor ($Can731). A break-even analysis showed that up to 80% of the study cohort could be treated with celecoxib instead of the NSAID-alone regimen without increasing the health system's overall budget. Celecoxib was associated with the fewest GI-related deaths, hospitalised events; symptomatic ulcers, and cases of anaemia. The celecoxib regimen was also associated with the fewest cases of upper GI distress. Sensitivity analyses revealed that the model was most sensitive to the distribution of GI risk in the population and to the ingredient costs of the treatment alternatives. CONCLUSIONS: This model indicates that the use of celecoxib could lead to the avoidance of a significant number of NSAID-attributable GI adverse events, and the incremental cost of using celecoxib for arthritis patients > or = 65 years of age in place of current treatment alternatives would not impose an excessive incremental impact on a Canadian provincial healthcare budget.

Modelling the cost effectiveness of lamivudine/zidovudine combination therapy in HIV infection.

The use of combination antiretroviral therapy is supported by clinical evidence for its superiority over monotherapy. Lamivudine (3TC) has been studied in combination with zidovudine (ZDV) and is recommended for use specifically in combination therapy. With the associated increase in drug acquisition cost, the economics of combination therapy versus monotherapy warrant study. An economic evaluation was undertaken to compare 3TC/ZDV combination therapy with ZDV monotherapy, taking a UK public finance perspective. The cost effectiveness of each of the 2 treatments was estimated using a Markov model of progression through 3 HIV-positive disease states: (i) CD4 cells > 200 and < 500 cells/mm3; (ii) CD4 < 200 cells/mm3, non-AIDS; and (iii) AIDS to eventual death. Progression probabilities and life expectancy were derived from a cohort treated at Chelsea and Westminster Hospital in London, using data for 1987 to 1995, along with cost data for a ZDV intent-to-treat population for 1994 and 1995. The relative risk of progression for 3TC/ZDV compared with ZDV monotherapy was estimated from meta-analysis of 4 completed comparative trials. To predict the effect of 3TC/ZDV on life expectancy and lifetime costs, progression probabilities were adjusted by the relative risk statistic for the duration of treatment with 3TC/ZDV. On the basis of an estimated relative risk of progression of 0.509 (95% CI 0.365 to 0.710), treatment with 3TC/ZDV is predicted to yield an incremental cost-effectiveness ratio of Pounds 6276 (95% CI Pounds 5337 to Pounds 9075) per life year saved (discounted at 6% per year). Extensive sensitivity analyses were performed to test the effects of varying values of input parameters on the model results. Under reasonable assumptions, the predicted cost effectiveness of 3TC/ZDV combination therapy compares favourably with previously reported economic analyses of various HIV treatments.

Constructing health state preference values from descriptive quality of life outcomes: mission impossible?

Descriptive quality of life questionnaires are commonly administered in clinical trials, to evaluate outcomes from the patient's perspective alongside conventional clinical measures. When expressed in single index form as health state preference values (HSPVs), quality of life information is also relevant to economic evaluations. By combining HSPVs with survival information, quality adjusted life years (QALYs) may be derived for cost-utility analysis. Although HSPVs are rarely measured prospectively in cancer clinical trials, the UK Medical Research Council Cancer Therapy Committee recommends the routine administration of two specific quality of life questionnaires: the Rotterdam Symptom Checklist and the Hospital Anxiety Depression Scale. This study explores two potential methods for secondary derivation of HSPVs from these instruments, using data gathered in a clinical trial of two forms of radiotherapy for non-small cell cancer of the bronchus. The first method, secondary mapping to existing utility scales, was found to be infeasible from the above questionnaires. The second method used factor analysis to summarize the descriptive quality of life data collected through the questionnaires. This revealed five distinct factors prevalent in the trial population. Using these factors, simplified health state scenarios were developed from which direct measurement of HSPVs was feasible. As the resulting HSPVs and any QALYs that may be derived from them are cancer specific, their potential value in informing resource allocation would be limited to decisions within oncology services.