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| A randomized controlled trial of the cost-utility of second-generation antipsychotics in people with psychosis and eligible for clozapine |
| Davies L M, Barnes T R, Jones P B, Lewis S, Gaughran F, Hayhurst K, Markwick A, Lloyd H |
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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 objective was to assess the cost-effectiveness of clozapine compared with other second-generation antipsychotics in patients with treatment-resistant schizophrenia, considering the recent availability of generic clozapine, in the UK. The authors concluded that clozapine was likely to be cost-effective from the perspective of the UK National Health Service, but only if the willingness to pay for a quality-adjusted life-year was higher than £33,000. The study was well conducted and presented and the authors’ conclusions appear to be valid. Type of economic evaluation Study objective The objective was to assess the cost-effectiveness of clozapine in comparison with other second-generation antipsychotic (SGA)s in patients with treatment-resistant schizophrenia. The analysis considered the recent availability of generic clozapine in the UK. Interventions The interventions were clozapine compared with newer SGAs including risperidone, sertindole, olanzapine, quetiapine, ziprasidone, zotepine, and amisulpride Location/setting UK/primary and secondary care. Methods Analytical approach:This economic evaluation was based on a single study with a one-year time horizon. The authors stated that the analysis was carried out from the perspectives of the National Health Service (NHS), social support services, and patients, which closely represented the societal point of view.
Effectiveness data:The clinical evidence came from a multi-centre, rater-blind, randomised controlled trial (RCT) that enrolled 67 patients in the clozapine arm and 69 patients in the SGA arm, in the UK. The follow-up period was one year and the Quality of Life Scale provided the primary endpoint and was used to determine the appropriate sample size. The results were adjusted for baseline differences in clinical characteristics between the patient groups and missing data were imputed by linear interpolation.
Monetary benefit and utility valuations:Utility valuations were derived from the RCT using the European Quality of life (EQ-5D) questionnaire at 12, 26, and 52 weeks from baseline randomisation.
Measure of benefit:Quality-adjusted life-years (QALYs) were the summary benefit measure.
Cost data:The economic items included hospital in-patient and out-patient services, primary and community care services, and prescribed medications. The resource use was based on the actual consumption of resources in the RCT. Costs came from the RCT and published national unit cost data, such as the Hospital Trust Financial Returns, the British National Formulary, and the Personal Social Services Research Unit at the University of Kent. All costs were in UK pounds sterling (£) for the 2005 to 2006 price year.
Analysis of uncertainty:Uncertainty was investigated in several ways. Firstly, the costs and benefits were adjusted to control for the effect of potentially confounding baseline variables using regression analyses. Secondly, bootstrapping was used to derive estimates of the imputed costs and QALYs, and cost-effectiveness acceptability curves. Thirdly, a deterministic analysis was carried out by changing the assumptions on drug costs, using alternative sources of data, and adjusting for out-patient initiation of drug therapy. Results Clozapine led to a gain of 0.05 QALYs (standard error, SE: 0.03, 95% confidence interval, CI: -0.02 to 0.11) and to an additional cost of £1,662 (SE: 3,466, 95% CI: -8,455 to 5,131) in comparison with SGAs.
Under the base-case conditions, the incremental cost per QALY gained with clozapine over SGAs was £33,240 and it ranged from £23,000 to £70,000 in the sensitivity analyses.
The cost-effectiveness acceptability curve indicated that, at a willingness to pay threshold of £35,000 per QALY, the probability of clozapine being cost-effective was 52%.
In the sensitivity analysis, only the adjustment for whether the initiation of the allocated drug therapy was likely to be a reason for in-patient admission, improved the cost-effectiveness of clozapine. The incremental cost-effectiveness ratio for clozapine compared with the other SGAs increased if unadjusted costs and QALYs were used. Authors' conclusions The authors concluded that clozapine was likely to be a cost-effective alternative to SGAs from the perspective of the NHS in the UK, but only if the willingness to pay for a QALY was over £33,000. CRD commentary Interventions:The selection of the comparators was appropriate in that clozapine was compared with other SGAs, which included risperidone, sertindole, olanzapine, quetiapine, ziprasidone, zotepine, and amisulpride. The type of non-clozapine SGA was based on the choice made by both clinicians and patients and reflected the normal clinical practice in the setting. First generation, conventional antipsychotics were considered to be less effective than SGAs.
Effectiveness/benefits:The clinical evidence came from a RCT, which represents a high-quality source of data, given the strengths of its design. Only some key features of the trial were presented, because it had been published elsewhere, but its internal validity appears to have been high as it used appropriate statistical tests to improve the reliability of the clinical estimates. The trial was carried out in a variety of practice settings that reflected the range of routine care in the UK, which improves the external validity. However, the authors acknowledged some limitations of the trial, such as the small sample size. The derivation of utility valuations for the calculation of QALYs was described, and a validated instrument was used. In general, the clinical analysis appears to have been carried out reliably.
Costs:The economic analysis was performed in accordance with the perspective in terms of both the categories of costs and their sources. The unit costs were not presented separately from the resource quantities, but the expected costs were broken down on the basis of time frames, cost category, location, and patient status at baseline. The price year was reported, which enhances the transparency of the economic analysis. The use of statistical tests was appropriate to determine a precise estimation of the total costs.
Analysis and results:The approaches used to synthesise the costs and benefits and to investigate the issue of uncertainty were appropriate. A strong aspect of the study was the extensive and clear presentation of the findings. The assumptions made for data manipulation and missing data were explicitly reported. The authors noted some possible limitations. Firstly, the sample size of the RCT was small and the study had insufficient power to detect statistically significant differences in the costs or QALYs. Secondly, the EQ-5D, although a validated instrument in schizophrenia, might not capture small but important changes in health status. Thirdly, the loss to follow-up, and the subsequent requirement for data imputation, may have affected the validity of the final estimates for the clinical endpoints and resource consumption, especially as the imputation approach was a determinant of the cost-utility ratios. Lastly, some categories of costs such as those for contacts with the criminal justice system, use of residential accommodation, and informal care were not included, thus total costs may have been underestimated.
Concluding remarks:The study was well conducted and presented and the authors’ conclusions appear to be valid. Funding Supported by a grant from the UK NHS Technology Assessment Programme. Bibliographic details Davies L M, Barnes T R, Jones P B, Lewis S, Gaughran F, Hayhurst K, Markwick A, Lloyd H. A randomized controlled trial of the cost-utility of second-generation antipsychotics in people with psychosis and eligible for clozapine. Value in Health 2008; 11(4): 549-562 Other publications of related interest Bagnall AM, Jones L, Ginnelly L, et al. A systematic review of atypical antipsychotic drugs in schizophrenia. Health Technol Assess 2003;7:1-204.
Aitchison K, Kerwin RW. Cost effectiveness of clozapine. Br J Psychiatry 1997;171:125-30.
Palmer CS, Brunner E, Ruiz-Flores LG, et al. A cost effectiveness decision analysis model for treatment of schizophrenia. Arch Med Res 2002;33:572-80.
Karki SD, Bellnier TJ, Patil K, et al. Cost effectiveness of atypical antipsychotics in severely and persistently mentally ill patients with schizophrenia and schizoaffective disorders. Drug Benefit Trends 2001;13:7-12. Indexing Status Subject indexing assigned by NLM MeSH Antipsychotic Agents /economics /therapeutic use; Clozapine /economics /therapeutic use; Cost-Benefit Analysis /economics; Great Britain; Health Status Indicators; Humans; Models, Economic; Psychotic Disorders /drug therapy /economics; Quality-Adjusted Life Years AccessionNumber 22008101572 Date bibliographic record published 24/06/2009 Date abstract record published 12/08/2009 |
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