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Long-term cost-effectiveness of donepezil for the treatment of Alzheimer's disease |
Teipel S J, Ewers M, Reisig V, Schweikert B, Hampel H, Happich 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 The study determined the cost-effectiveness of donepezil, compared with current care (placebo), for the treatment of Alzheimer's disease in the German setting. The authors concluded that donepezil was a potentially cost-effective alternative to placebo, although the results were highly dependent on the assumptions about treatment effectiveness and remuneration of care-giving. The quality of the study methodology was generally good, although more detailed reporting of both the economic and clinical sides of the analysis would have been useful. Type of economic evaluation Cost-effectiveness analysis, cost-utility analysis Study objective The objective of the study was to determine the cost-effectiveness of donepezil, an (acetyl-)cholinesterase inhibitor used for the treatment of Alzheimer's disease (AD), in the German setting in comparison with current care. The study focused on the long-term effects of treatment and multiple types of costs associated with AD. Interventions The study examined the use of donepezil (10 mg/day) in the treatment of AD. It was compared with placebo. Methods Analytical approach:This economic evaluation was based on a Markov model, which simulated the progression of AD severity through the course of the disease. The time horizon of the analysis was 5 years (10 years in the alternative scenario). The authors stated that the perspective adopted in the study was that of the reimbursement system in Germany, with a differentiation between health and nursing care insurances.
Effectiveness data:The clinical data appear to have been obtained from a selection of known studies. Transition probabilities and severity specific mortality rates were derived from a Swedish population-based study that followed a group of elderly people for more than 4 years. The efficacy of donepezil was estimated from a multi-centre, randomised controlled trial (RCT) that had been conducted in the USA. The authors made assumptions about mortality. The distribution of initial disease severity came from a database at a local hospital, with a total of 570 patients examined. The key clinical estimate was the treatment effect of donepezil in reducing AD progression.
Monetary benefit and utility valuations:Health-related quality of life was estimated from a published cross-sectional study that used the Health Utilities Index Mark II provided by caregivers.
Measure of benefit:The summary benefit measures were the numbers of quality-adjusted life-years (QALYs) and life-years (LYs). These were estimated using the decision model. A discount rate of 5% was applied to both benefit measures.
Cost data:The analysis of the costs considered drug costs, hospital costs (length of stay), outpatient costs and remuneration of time devoted to care by families. The costs of care were strictly dependent on the severity of disease, which determined the degree of institutionalisation. The costs of donepezil were based on the German drug register. Other costs were derived from a survey of 1,682 German AD patients. The sources of the resource use data were not reported for all items. The costs were in euros (EUR). The costs were discounted at an annual rate of 5% and the price year was 2004.
Analysis of uncertainty:A deterministic sensitivity analysis was performed to establish the robustness of model results to variations in clinical and economic assumptions. Alternative values appear to have been based on authors' opinions. A threshold analysis was also performed to identify the parameter values at which donepezil became cost-saving. Results The expected costs were EUR 25,321 with placebo and EUR 25,584 with donepezil. The expected LYs were 3.00 with placebo and 3.06 with donepezil, while the expected QALYs were 1.48 and 1.54, respectively.
Incremental ratios were calculated in order to combine the costs and benefits of the two strategies. The incremental cost per LY gained with donepezil over placebo was EUR 4,937, while the incremental cost per QALY gained was EUR 4,264.
The sensitivity analysis showed that the results were very sensitive to assumptions about the efficacy of donepezil and the remuneration of care-giving activity. For example, if donepezil reduces disease progression by only 20% per year, the incremental cost per QALY gained would be EUR 16,726, whilst given a 54% reduction of disease progression, donepezil would be dominant (i.e. more effective and less expensive). Similarly, donepezil would be dominant if the hourly remuneration of care-giving were set at EUR 5 (EUR 0 in the base-case). Variations in other inputs resulted in slight changes in the cost-effectiveness figure, but did not make donepezil cost-saving. Authors' conclusions The authors concluded that donepezil was a potentially cost-effective alternative to placebo for the treatment of AD in the German setting, although the results were highly dependent on the assumptions about treatment effectiveness and remuneration of care-giving. CRD commentary Interventions:The selection of the comparators was appropriate given that a new intervention, namely donepezil, was compared with the current pattern of care for AD patients. In effect, donepezil was considered as an adjunct to standard care rather than as an alternative strategy. Donepezil is also likely to represent a valid option in other settings.
Effectiveness/benefits:The clinical evidence was based on a selection of known relevant studies, which might have been identified selectively since the conduct of a systematic review of the literature was not reported. The authors stated that information on treatment effectiveness was derived from a multi-centre RCT, details of which were not reported. Although the provision of more information about the main source of data on treatment effectiveness would have been helpful, the use of an RCT represents a strength of the analysis. It was pointed out that the clinical data were taken from studies performed in Sweden and the USA, thus their applicability to the German context may be an issue. However, conservative estimates were used in order not to bias the analysis in favour of donepezil. The derivation of the benefit measure was based on a published study, brief details of which were provided. The use of both LYs and QALYs represents an appropriate approach and will enable comparisons with other published economic evaluations.
Costs:The analysis of the costs considered a broad perspective, and all the relevant categories of costs appear to have been included. Although the authors explained the method used to calculate the costs, the unit costs and the resource quantities were not presented separately. The sources of the costs were reported, but information on the sources of resource consumption was not clear for all items. The price year was reported, which will aid reflation exercises in other settings. The cost data were treated deterministically in both the base-case and the sensitivity analysis.
Analysis and results:The costs and benefits were appropriately synthesised using incremental ratios. The issue of uncertainty was addressed in the sensitivity analysis, in which all model inputs were varied across a plausible range. However, the use of a more sophisticated analysis (e.g. a probabilistic sensitivity analysis) would have been interesting given the uncertainty surrounding more than one parameter of the model. The results of the sensitivity analysis were presented selectively. The issue of the generalisability of the study results to other settings was not explicitly addressed. The authors compared the results of this study with other published findings that showed important differences in cost-effectiveness ratios among the published evidence.
Concluding remarks:The quality of the study methodology was satisfactory, although more detailed reporting of the methods and results would have been helpful. Caution is required when interpreting the study results, owing to the strong impact of some uncertain estimates on the cost-effectiveness results. Bibliographic details Teipel S J, Ewers M, Reisig V, Schweikert B, Hampel H, Happich M. Long-term cost-effectiveness of donepezil for the treatment of Alzheimer's disease. European Archives of Psychiatry and Clinical Neuroscience 2007; 257: 330-336 Other publications of related interest Kmietowicz Z. NICE proposes to withdraw Alzheimer’s drugs from NHS. BMJ 2005;330:495.
Jonsson L, Lindgren P, Wimo A, et al. The cost-effectiveness of donepezil therapy in Swedish patients with Alzheimer’s disease: a Markov model. Clin Ther 1999;21:1230-40.
Neumann PJ, Hermann RC, Kuntz KM, et al. Cost-effectiveness of donepezil in the treatment of mild or moderate Alzheimer’s disease. Neurology 1999;51:1138-45.
O’Brien BJ, Goeree R, Hux M et, al. Economic evaluation of donepezil for the treatment of Alzheimer’s disease in Canada. J Am Geriartr Soc 1999;47:570-8. Indexing Status Subject indexing assigned by NLM MeSH Aged; Alzheimer Disease /drug therapy /economics /psychology; Cost-Benefit Analysis; Costs and Cost Analysis; Data Interpretation, Statistical; Female; Germany; Health Care Costs; Health Status Indicators; Humans; Indans /economics /therapeutic use; Long-Term Care; Male; Markov Chains; Nootropic Agents /economics /therapeutic use; Patient Care Planning /economics; Piperidines /economics /therapeutic use; Quality-Adjusted Life Years AccessionNumber 22007002206 Date bibliographic record published 09/08/2008 Date abstract record published 01/09/2008 |
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