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Cost effectiveness of ezetimibe in patients with cardiovascular disease and statin intolerance or contraindications: a Markov model |
Ara R, Pandor A, Tumur I, Paisley S, Duenas A, Williams R, Rees A, Wilkinson A, Durrington P, Chilcott J |
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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 examine the cost-effectiveness of long-term ezetimibe (EZE) monotherapy in comparison with no treatment in patients with established cardiovascular disease and high low-density lipoprotein cholesterol levels, who do not tolerate statins or in whom they are contraindicated. The analysis demonstrated that EZE was a cost-effective alternative to no treatment in this specific patient population. On the whole, the study was well conducted and described. The authors’ conclusions appear to be valid and robust. Type of economic evaluation Study objective The objective was to examine the long-term cost-effectiveness of ezetimibe (EZE) monotherapy in comparison with no treatment in patients with established cardiovascular disease (CVD) and high low-density lipoprotein cholesterol (LDL-C) levels who do not tolerate statins, or in whom they are contraindicated. Interventions EZE at a dose of 10mg per day was compared with no treatment. Methods Analytical approach:This economic evaluation was used a modified published Markov model, with a lifetime horizon. The authors stated that the analysis was carried out from the perspective of the UK Department of Health.
Effectiveness data:The clinical data came from multiple published sources. The efficacy of EZE was based on a meta-analysis of randomised controlled trials (RCTs), which were identified through a systematic review of published evidence. The details of the meta-analytic approach were reported. Similarly, the link between changes in LDL-C levels and the reduction in CVD events was obtained from a published meta-analysis. Other epidemiological inputs came from UK sources such as the British Heart Foundation or the Nottingham Heart Attack Register. These sources were known to and selected by the authors. The primary clinical input for the model was the reduction in LDL-C level associated with EZE.
Monetary benefit and utility valuations:The utility valuations were derived from published studies which were identified through a systematic review of the literature. The European Quality of life (EQ-5D) questionnaire preference-based utility data were selected whenever possible. Expert opinion was also used to assess the impact of subsequent CVD events on the utility weights.
Measure of benefit:Quality-adjusted life-years (QALYs) were used as the summary benefit measure and a 3.5% annual discount rate was applied.
Cost data:The economic analysis included the costs of drugs and health care resources associated with each health state (i.e. myocardial infarction, angina, transient ischaemic attack, and stroke). The drug costs were taken from the British National Formulary, while costs for different health conditions came from the published literature. These sources were presumably used to derive data on resource consumption patterns. The price year was 2006. All costs were in UK pounds sterling (£) and were discounted at a 3.5% annual rate.
Analysis of uncertainty:The issue of uncertainty was investigated by means of a probabilistic analysis and a Monte Carlo simulation, with probabilistic distributions being assigned to all the model inputs. Furthermore, a series of one-way sensitivity analyses was performed on the key model inputs. The ranges of values were presumably derived from the literature or defined by the authors. Different scenarios for the patients’ baseline characteristics, such as age, gender, and age of treatment commencement, were considered. Results In a hypothetical cohort of 1,000 males aged 55 years, the lifetime QALYs gained with EZE over no treatment were 211 and the additional costs were £4,860,810.
The mean incremental cost per QALY gained with EZE was £23,026 (confidence interval: £22,979 to £23,074). For a cohort of patients aged 75 years the incremental cost per QALY was £29,582.
The deterministic sensitivity analysis showed that the majority of the results remained below the threshold of £30,000 per QALY under different scenarios (e.g. a female cohort, different ages, and changes in the health utilities). However, the most influential model inputs were the discount rate, advanced age, the relative risk for LDL-C relationship, and the utility values.
The probabilistic sensitivity analysis showed that EZE had a 99% probability of being cost-effective at a threshold of £30,000 per QALY. Authors' conclusions The authors concluded that EZE was a cost-effective alternative to no treatment for this specific population. CRD commentary Interventions:The selection of the strategies was appropriate. EZE was licensed in Europe as an additional therapy to dietary change for the treatment of hypercholesterolaemia in patients for whom a statin was considered inappropriate or not tolerated.
Effectiveness/benefits:The authors described the method used to identify the relevant clinical inputs. The meta-analysis of RCTs was a valid source of data for two reasons. Firstly, RCTs are considered a robust source of evidence given the strengths of their design. Secondly, the meta-analytic approach was described, including the statistical methods, which were used to combine the primary data and to deal with the issue of heterogeneity. The details of the derivation of the efficacy of treatment were provided. Less detailed information on the other sources of data was provided, but the use of official registers is a common and validated source of epidemiological data. In general, the approach used to derive the clinical inputs for the model appears to have been appropriate. QALYs were an appropriate benefit measure with which to capture the impact of the interventions on the patients’ health, both in terms of quality of life, and survival. The derivation of the utility valuations was based on published studies, which used a validated instrument.
Costs:The analysis of costs appears to have been consistent with the economic viewpoint. A breakdown of the cost categories was not provided as only macro-costs were presented. This approach reduces the transparency of the economic analysis, especially as the costs were derived from previous studies, the methodologies of which were not reported. Nevertheless, the calculation of costs related to health conditions is a common approach for diseases such as CVD. Other aspects of the analysis, such as the price year, the source of the cost of EZE, the use of discounting, and the probabilistic distributions assigned to the economic data, were reported in detail. Finally, the costs were widely varied in the deterministic sensitivity analysis, to determine whether the study findings were robust.
Analysis and results:The use of an incremental approach to synthesise the costs and benefits was appropriate given the higher costs and QALYs associated with EZE. The issue of uncertainty was satisfactorily addressed using both a probabilistic and a deterministic approach. The results of the base-case and the sensitivity analyses were clearly presented and discussed. The authors pointed out that a conservative approach was used whenever possible in order to reduce the uncertainties of the modelling framework. The issue of the generalisability of the study findings was not specifically investigated. The results of this study were specific to the patient population analysed, which represented between 1% and 3% of the total population receiving statins in the UK.
Concluding remarks:On the whole, the study was well conducted and described. The authors’ conclusions appear to be valid and robust. Funding Funded by the UK National Coordinating Centre for Health Technology Assessment. Bibliographic details Ara R, Pandor A, Tumur I, Paisley S, Duenas A, Williams R, Rees A, Wilkinson A, Durrington P, Chilcott J. Cost effectiveness of ezetimibe in patients with cardiovascular disease and statin intolerance or contraindications: a Markov model. American Journal of Cardiovascular Drugs 2008; 8(6): 419-427 Other publications of related interest Ara R, Tumur I, Pandor A, et al. Ezetimibe for the treatment of hypercholesterolaemia: a systematic review and economic evaluation. Health Technol Assess 2008;12:1-212.
Kohli M, Attard C, Lam A, et al. Cost effectiveness of adding ezetimibe to atorvastatin therapy in patients not at cholesterol treatment goal in Canada. Pharmacoeconomics 2006;24:815-30.
Cook JR, Yin D, Alemao E, et al. Cost-effectiveness of ezetimibe coadministration in statin-treated patients not at cholesterol goal: application to Germany, Spain, and Norway. Pharmacoeconomics 2004;22:49-61. Indexing Status Subject indexing assigned by NLM MeSH Age Factors; Anticholesteremic Agents /economics /therapeutic use; Azetidines /economics /therapeutic use; Cardiovascular Diseases /economics /etiology /prevention & Cholesterol, LDL /blood; Cohort Studies; Cost-Benefit Analysis; Ezetimibe; Great Britain; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors /adverse effects /contraindications; Hypercholesterolemia /complications /drug therapy /economics; Male; Markov Chains; Middle Aged; Models, Economic; Quality-Adjusted Life Years; control AccessionNumber 22009100726 Date bibliographic record published 07/04/2009 Date abstract record published 27/05/2009 |
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