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Modelling the long term cost effectiveness of clopidogrel for the secondary prevention of occlusive vascular events in the UK |
Karnon J, Brennan A, Pandor A, Fowkes G, Lee A, Gray D, Coshall C, Nicholls C, Akehurst R |
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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. Health technology The study investigated treatment with clopidogrel (75 mg/day) for 2 years, followed by acetylsalicylic acid (aspirin; ASA 325 mg/day) for the remaining lifetime of the patient. This intervention was compared with ASA alone (325 mg/day) for life.
Economic study type Cost-effectiveness analysis and cost-utility analysis.
Study population The study population comprised a hypothetical cohort of 1,000 UK patients aged 60 years with the qualifying diagnoses of myocardial infarction (MI), ischaemic stroke and peripheral arterial disease, who were at risk of secondary OVEs (i.e. nonfatal MI, nonfatal stroke or vascular death).
Setting The setting was secondary care. The economic study was carried out in the UK.
Dates to which data relate The effectiveness data were derived from studies published between 1993 and 2002. The price year was 2003.
Source of effectiveness data The effectiveness data were derived from a review and synthesis of published data.
Modelling A Markov model was used to simulate the transition of patients through a series of discrete health states over the lifetime of the patient, up to a maximum of 40 years. The discrete health states were new MI, post new MI, new stroke, post new stroke and death.
Outcomes assessed in the review The outcomes assessed in the review were;
the vascular event rates in patients treated with ASA aged 60 and 90 years;
the relative risk (RR) of MI in patients treated with clopidogrel as opposed to ASA;
the RR of stroke in patients treated with clopidogrel as opposed to ASA;
the RR of vascular death in patients treated with clopidogrel as opposed to ASA;
the composite RR of patients treated with clopidogrel as opposed to ASA.
Study designs and other criteria for inclusion in the review RRs were derived from the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial, which was a multi-centre randomised controlled trial in 19,185 patients. Event rates were derived from epidemiological studies.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included Approximately 14 primary studies were included in the review of the literature. Event rates were derived from three main data sources, which were used to quantify representative event rates. RRs were derived from the CAPRIE trial.
Methods of combining primary studies Investigation of differences between primary studies Results of the review The RR of MI in patients treated with clopidogrel as opposed to ASA was 0.8315 (95% confidence interval, CI: 0.6980 to 0.9910).
The RR of stroke in patients treated with clopidogrel as opposed to ASA was 0.9356 (95% CI: 0.8180 to 1.0700).
The RR of vascular death in patients treated with clopidogrel as opposed to ASA was 0.9531 (95% CI: 0.8160 to 1.1130).
The composite RR of patients treated with clopidogrel as opposed to ASA was 0.913 (95% CI: 0.835 to 0.997).
Measure of benefits used in the economic analysis The health benefit measures used were the life-years (LYs) and quality-adjusted life-years (QALYs) gained. The utility values for the stroke states in the model were taken from a quality of life meta-analysis. Data for the remaining utility values were taken from the Harvard Utilities database.
Direct costs The direct costs of the health care system were included in the analysis. These were the costs of medications and of treating recurrent events (i.e. MI, stroke and peripheral arterial disease). The unit cost of medications was derived from the British National Formulary. The costs for each of the six possible health states in the model were derived from a variety of UK-specific sources (i.e. published studies). Discounting was relevant, as the costs could be incurred over the lifetime of the patient, therefore all future costs were appropriately discounted. The authors used an annual rate of 6% in accordance with the 2001 guidelines of the National Institute for Clinical Excellence. The study reported the total costs. The price year was 2003.
Statistical analysis of costs The costs were treated as point estimates (i.e. the data were deterministic).
Indirect Costs The indirect costs were not included.
Sensitivity analysis The authors undertook a series of one- and two-way sensitivity analyses to investigate the stability of the base-case estimates. Variables investigated in the sensitivity analyses were health state costs, compliance and effectiveness, utility estimates and the RRs for the individual outcomes. The authors also performed a probabilistic sensitivity analysis in which each key parameter was varied randomly at the same time within a defined sample distribution. Simulations were performed 1,000 times to produce a cost-effectiveness acceptability curve.
Estimated benefits used in the economic analysis The total number of LYs gained over the lifetime of 1,000 patients was 14,199 for ASA-treated patients versus 14,242 for clopidogrel-treated patients.
The total number of QALYs gained over the lifetime of 1,000 patients was 11,964 for ASA-treated patients versus 12,002 for clopidogrel-treated patients.
Cost results The total costs incurred by the 1,000 ASA-treated patients were 18,380,509, compared with 19,199,554 for the 1,000 clopidogrel-treated patients.
Synthesis of costs and benefits The costs and benefits were combined using an incremental cost-effectiveness ratio (i.e. the additional cost per LY gained) and an incremental cost-utility ratio (i.e. the additional cost per QALY gained).
Compared with ASA, the incremental cost-effectiveness ratio of treating patients with clopidogrel was 18,888 per LY gained and the incremental cost-utility ratio was 21,489 per QALY gained.
The authors reported that the results of the one- and two-way sensitivity analyses suggested that the model was robust to variations in a wide range of input parameters. The results of the probabilistic sensitivity analysis showed that, at a 30,000 per QALY decision threshold, the probability of clopidogrel being cost-effective was approximately 60%.
Authors' conclusions Two years of treatment with clopidogrel could be considered a cost-effective intervention in patients at risk of secondary occlusive vascular events (OVEs) in the UK.
CRD COMMENTARY - Selection of comparators A justification was given for using ASA as the comparator. It was recommended in the UK that patients at risk of secondary OVEs receive 75 to 150 mg/day ASA indefinitely. You should decide if the comparator used represents current practice in your own setting.
Validity of estimate of measure of effectiveness The authors did not report that a systematic review of the literature was undertaken to identify relevant research and minimise bias. The majority of the effectiveness parameters were derived from the CAPRIE trial, a very large multi-centre randomised controlled trial. This study would appear to be the 'gold' standard study design, so the results used in the model would appear to be valid. The authors supplemented data from the CAPRIE trial with event rates derived from epidemiological studies in order to quantify representative event rates of patients treated with ASA. They also conducted a series of sensitivity analyses in which the effectiveness model parameters were varied.
Validity of estimate of measure of benefit The estimation of benefits was modelled using a Markov model. The model appears to have been appropriate and was well-defined in the article.
Validity of estimate of costs All the cost categories relevant to the health care system perspective adopted were included in the analysis. The authors reported that the costs of secondary OVEs, which were derived from published studies, were included in the analysis. However, they did not report which categories of cost were included in these studies, consequently it was unclear whether all the relevant costs were included in the analysis. The costs and the quantities were not reported separately, which will decrease the generalisability of the authors' results. The costs were derived from published sources. Appropriate sensitivity analyses were conducted. Since costs could be incurred over the lifetime of the patient, all future costs were appropriately discounted. The price year was reported, which will aid any future inflation exercises.
Other issues The authors reported that a review of the published economic evaluations of clopidogrel had shown that no analyses had been undertaken from a UK National Health Service perspective. The issue of generalisability to other settings was addressed in the sensitivity analysis. The authors do not appear to have presented their results selectively and their conclusions reflected the scope of the analysis. The authors reported a number of further limitations to their study. First, the CAPRIE trial was not designed with economic analyses in mind, so issues such as statistical power, patient predisposition and other entry criteria could detract from the generalisability of the results. Second, the CAPRIE trial did not assess treatment with clopidogrel after the initial 2-year period.
Implications of the study The authors recommended that further research should focus on the pathophysiology of atherothrombotic diseases to determine how clopidogrel therapy influences the vascular system and disease activity and progression, and whether the disease process is temporarily inhibited by clopidogrel, only to recommence shortly after cessation of clopidogrel treatment.
Source of funding Supported by Sanofi-Synthelabo and Bristol-Myers Squibb.
Bibliographic details Karnon J, Brennan A, Pandor A, Fowkes G, Lee A, Gray D, Coshall C, Nicholls C, Akehurst R. Modelling the long term cost effectiveness of clopidogrel for the secondary prevention of occlusive vascular events in the UK. Current Medical Research and Opinion 2005; 21(1): 101-112 Other publications of related interest Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information
CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329-39.
Annemans L, Lamotte M, Levy E, et al. Cost-effectiveness analysis of clopidogrel versus aspirin in patients with atherothrombosis based on the CAPRIE trial. J Med Econ 2003;6:43-56.
Ho WK, Hankey GJ, Eikelboom JW. Prevention of coronary heart disease with aspirin and clopidogrel: efficacy, safety, costs and cost-effectiveness. Expert Opin Pharmacother 2004;5:493-503.
Gaspoz JM, Coxson PG, Goldman PA, et al. Cost effectiveness of aspirin, clopidogrel or both for secondary prevention of coronary heart disease. New Engl J Med 2002;346:1800-6.
Indexing Status Subject indexing assigned by NLM MeSH Aged; Aspirin /economics /therapeutic use; Cost-Benefit Analysis; Female; Great Britain; Humans; Male; Markov Chains; Middle Aged; Models, Economic; Platelet Aggregation Inhibitors /economics /therapeutic use; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Ticlopidine /analogs & Vascular Diseases /economics /prevention & control; derivatives /economics /therapeutic use AccessionNumber 22005000434 Date bibliographic record published 28/02/2007 Date abstract record published 28/02/2007 |
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