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A 1-year prospective cost-effectiveness analysis of roflumilast for the treatment of patients with severe chronic obstructive pulmonary disease |
Rutten-van Molken M P, van Nooten F E, Lindemann M, Caeser M, Calverley P M |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. CRD summary This study compared the cost-effectiveness of roflumilast against placebo for the treatment of patients with severe to very severe chronic obstructive pulmonary disease. Roflumilast increased costs without significantly improving effectiveness or quality of life, but it could be cost-saving for very severe patients. The analysis was transparent and credible and the authors' conclusions appear to be appropriate, but sensitivity analysis around the assumed cost of roflumilast is needed to demonstrate that these results are robust. Type of economic evaluation Cost-effectiveness analysis Study objective This study compared the effectiveness of drugs for the management of patients with severe to very severe chronic obstructive pulmonary disease (COPD) according to the guidelines of the Global Initiative for Chronic Lung Disease (GOLD). Interventions The intervention was oral roflumilast 500μg once daily and this was compared with placebo. Roflumilast is an anti-inflammatory agent, which inhibits phosphodiesterase IV. Methods Analytical approach:This economic evaluation was based on a single study with a one-year time horizon. The authors reported that the societal and the UK National Health Service (NHS) perspectives were adopted.
Effectiveness data:The clinical evidence came from a multi-centre (159 centres in 14 countries) randomised, double-blind, placebo-controlled, parallel group, clinical trial. A sample of 1,829 patients was enrolled. Of these, only 1,514 were randomised, with 761 in the roflumilast group (25% female) and 753 in the placebo group (23.8% female). They were analysed on an intention-to-treat basis. Further details were published elsewhere (Fabbri, et al. 2006, Calverley, et al. 2006, see ‘Other Publications of Related Interest’ below for bibliographic details). The length of the follow-up was one year and data were collected at four, eight, 12, 20, 28, 36, 44 and 52 weeks. Missing values were analysed using a multiple imputation technique. The primary outcome was the rate of moderate or severe exacerbations.
Monetary benefit and utility valuations:None.
Measure of benefit:The benefit measures were the number of moderate or severe exacerbations avoided and disease-specific quality-of-life improvement, which was defined as an improvement in St George’s Respiratory Questionnaire (SGRQ) score of four or more units between initiation and one year of treatment.
Cost data:Health care costs and productivity losses due to work absence were considered. The health care costs included medication, hospitalisation, contacts with health care professionals, ambulance transportation, and laboratory tests. The productivity costs were estimated based on absence from work and days of inactivity due to illness. The friction cost approach was used with a friction period derived from the literature. The resource use was based on actual consumption of services, using a health economics case report form (HE-CRF), and data from medical records and patient interviews. The costs were derived from official price lists such as the NHS Reference Costs and the Personal Social Services Research Unit. The cost of roflumilast was based on an authors’ assumption. All costs were converted from UK pounds sterling (£) to Euros (EUR) and the price year was 2004.
Analysis of uncertainty:In a sensitivity analysis, the uncertainty was assessed around the analytical methods for imputation and the calculation of productivity costs. Parameter uncertainty was assessed around the unit costs of hospital days and the inclusion of total costs as an alternative to COPD-related costs. The different methods and the ranges used were reported. The uncertainty around the cost-effectiveness results was analysed using bootstrapping and cost-effectiveness planes and cost-effectiveness acceptability curves were generated. Sub-groups were analysed based on COPD severity. Results From a societal perspective, the mean cost per patient was EUR 1,637 for roflumilast and EUR 1,401 for placebo. From the NHS perspective, the costs were EUR 1,418 for roflumilast and EUR 1,242 for placebo. These cost differences were not statistically significant.
The mean number of moderate or severe exacerbations per patient was 0.96 for roflumilast and 1.06 for placebo. This difference was not statistically significant. For very severe patients the difference was 0.6 exacerbations avoided and this was statistically significant. The proportion of patients with an improvement in SGRQ score (four or more units) was 0.19 for roflumilast and 0.14 for placebo and the difference was not statistically significant.
From a societal perspective, the incremental cost per moderate or severe exacerbation avoided was EUR 2,356 and the incremental cost per additional patient with an improved SGRQ score was EUR 4,712. From the NHS perspective, the ratios were EUR 1,755 per exacerbation avoided and EUR 3,510 per improved SGRQ. In the sub-group of very severe COPD patients, total costs were lower in the roflumilast group compared with placebo.
From a societal perspective, the cost-effectiveness acceptability curve indicated that, at a willingness-to-pay threshold of EUR 5,000 per exacerbation avoided, the probability of roflumilast being cost-effective was 70% and at a threshold of EUR 50,000 it was 90%. For an additional patient with improved SGRQ at a willingness to pay of EUR 20,000 roflumilast had a probability greater than 70% of being cost-effective. For very severe COPD patients, at a willingness to pay of EUR 0 per exacerbation avoided, roflumilast had a 92% probability of being cost saving.
Sensitivity analyses demonstrated that these results were sensitive to the method of imputation used, while they were relatively robust to the method used to estimate the productivity losses. The results were robust to variation in the cost estimates. Authors' conclusions The authors concluded that roflumilast increased costs and its effectiveness was not significantly different, in terms of exacerbations avoided and improvement in disease-specific quality of life, when compared with placebo. The analysis demonstrated that roflumilast was cost-effective only for very severe COPD patients due to a significant reduction in exacerbations compared with placebo. CRD commentary Interventions:The authors chose placebo as a comparator for roflumilast. This allowed the active value of the treatment to be evaluated, but will not allow comparisons with other active treatments for COPD, and so this may have been a partial decision analysis.
Effectiveness/benefits:The clinical data were derived from a randomised, double-blind, placebo-controlled trial, which is usually considered to be a high quality source of evidence given its robust design. The analysis of the clinical data was based on the intention-to-treat method which makes the comparison more robust. The measurement of patients’ quality of life was derived using patient questionnaires (SGRQ). This was a disease-specific measure of benefit and does not allow cross-disease comparisons and comparisons with other health interventions. The methods used to handle missing data were reported and appear to have been appropriate.
Costs:The costs were adequate for the perspective and the cost analysis was based on appropriate methodology. The unit costs and their sources were clearly presented and resource use was reported separately. Missing data were evaluated using appropriate methods. The level of reporting was adequate. The cost of roflumilast was based on authors’ assumptions, but this key parameter was not included in the sensitivity analysis.
Analysis and results:The synthesis of costs and benefits was appropriately performed. The authors addressed the issue of uncertainty around the analytical methods in detail, but the uncertainty around the assumed cost of roflumilast and its impact on the economic results was not addressed.
Concluding remarks:Overall, the methodology was good, with satisfactory reporting of the methods and results. Given the assumed cost of roflumilast, the authors' conclusions appear to be appropriate. Sensitivity analysis on this cost estimate is warranted to demonstrate that these results are robust. Funding Supported by ALTANA Pharma AG, Konstanz, Germany. Bibliographic details Rutten-van Molken M P, van Nooten F E, Lindemann M, Caeser M, Calverley P M. A 1-year prospective cost-effectiveness analysis of roflumilast for the treatment of patients with severe chronic obstructive pulmonary disease. PharmacoEconomics 2007; 25(8): 695-711 Other publications of related interest Fabbri LM, Sanchez-Toril F, McIvor RA, et al. Effect of roflumilast on exacerbations: a 1-year study in patients with severe to very severe COPD. Proc Am Thorac Soc 2006;3:A841.
Calverley PM, Sanchez-Toril F, McIvor RA, et al. Effect of roflumilast on lung function: a 1-year study in patients with severe to very severe COPD. Proc Am Thorac Soc 2006;3:A725. Indexing Status Subject indexing assigned by NLM MeSH Aged; Aminopyridines /economics /therapeutic use; Benzamides /economics /therapeutic use; Cost-Benefit Analysis; Cyclopropanes /economics /therapeutic use; Double-Blind Method; Female; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors /therapeutic use; Prospective Studies; Pulmonary Disease, Chronic Obstructive /drug therapy /psychology; Quality of Life AccessionNumber 22007001677 Date bibliographic record published 06/09/2007 Date abstract record published 14/10/2009 |
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