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An economic analysis of the Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS) |
Smith D G, McBurney C 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 use of atorvastatin (ATO; 10 - 80 mg/day), fluvastatin (FLU; 20 - 40 mg/day or 40 mg twice daily), lovastatin (LOV; 20 - 40 mg/day or 40 mg twice daily), pravastatin (PRA; 10 - 40 mg/day) and simvastatin (SIM; 10 - 40 mg/day) for the treatment of hypercholesterolaemia.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised patients with a low-density lipoprotein-cholesterol (LDL-C) level at least 30 mg/dL higher than the National Cholesterol Education Panel II (NCEP) target (stratified by risk factors) and a fasting triglyceride level of less than 400 mg/dL. The patients also had a confirmed negative serum pregnancy test. The exclusion criteria were known hypersensitivity to statins, use of prohibited medications (including cholesterol drugs not prescribed in the protocol), acute liver disease and uncontrolled diabetes. A further exclusion criterion was age older than 80 years or younger than 18 years.
Setting The setting was secondary care. The economic study was carried out in the USA.
Dates to which data relate The effectiveness and resource use data were gathered from May 1997 to January 1999. The price year was 2001.
Source of effectiveness data The effectiveness evidence was derived from a single study, the methods and results of which had been published already (Andrews et al., see Other Publications of Related Interest).
Link between effectiveness and cost data The costing was performed prospectively on the same sample of patients as that used in the effectiveness study.
Study sample The information on the study sample was limited as most of the methods had been published already. A total of 3,887 patients were included into the study sample. There were 1,944 patients(mean age 61.2 years in the ATO group, of which 39% were female and 11.8% were non-white. There were 493 patients (mean age 61.4 years) in the FLU group, of which 37.5% were female and 11.6% were non-white. There were 494 patients (mean age 61.4 years) in the LOV group, of which 39.9% were female and 8.9% were non-white. There were 478 patients (mean age 61.1 years) in the PRA group, of which 38.5% were female and 11.3% were non-white. There were 478 patients (mean age 60.8 years) in the SIM group, of which 42.3% were female and 11.1% were non-white. It was not stated whether some patients refused to participate, or were excluded from the study sample for any reason.
Study design This was a prospective, randomised, open-label clinical trial that was carried out at 153 centres across the USA. The patients were followed for 54 weeks. Patients were started at the lowest available dose and titrated at three or four 6-week intervals. The sample of patients who received at least one dose of the study medications and had at least one follow-up visit comprised 3,756 patients. The sample of patients who completed the study comprised 3,273 patients.
Analysis of effectiveness The analysis of the clinical study was based on the full sample of patients randomised (n=3,887). However, alternative analyses were conducted on an intention to treat basis (patients who received at least one dose of the study medications and had at least one follow-up visit; n=3,756 patients) and for treatment completers only (patients who completed the study; n=3,273).
The primary outcome measures used in the economic evaluation were the percentage of patients achieving NCEP-II LDL-C targets at the initial dose (week 6), and the percentage change in LDL-C from baseline to week 6. The NCEP-II LDL-C targets were 160 mg/dL (4.13 mmol/L) for patients with fewer than 2 risk factors, 130 mg/dL (3.36 mmol/L) for patients with 2 or more risk factors, and 100 mg/dL (2.59 mmol/L) for patients with established coronary heart disease or peripheral vascular disease. Medication-related adverse events were also considered. At baseline, the study groups were well balanced in terms of clinical and demographic characteristics.
Effectiveness results The percentage of patients reaching the LDL-C goal was 88% with ATO, 48% with FLU, 66% with LOV, 44% for PRA, and 76% with SIM, (p<0.01 for ATO versus all other statins).
ATO also remained significantly more effective in reaching LDL-C goals, compared with the other statins, in the intention to treat and treatment completers only samples. Medication-related adverse events were similar among groups.
Clinical conclusions The effectiveness analysis showed that ATO led to the highest percentage of patients achieving NCEP-II LDL-C targets at the initial dose.
Measure of benefits used in the economic analysis The summary benefit measure was the proportion of patients achieving NCEP-II LDL-C targets at the initial dose. This was derived directly from the effectiveness study.
Direct costs Discounting was not relevant since the costs were incurred during one year. The unit costs were presented separately from the quantities of resources used. The health services included in the economic evaluation were study medications, physician visits, laboratory tests, emergency room visits, other provider visits, diagnostic tests, and any facility service (including hospitalisation). The resources associated with the treatment of adverse events associated with the study medications were included. The cost/resource boundary of the study was that of the third-party payer. Resource use was estimated using patient-level data derived from the sample of patients included in the clinical trial. The costs were estimated from average wholesale prices (medications) and Medicare rates. The price year was 2001.
Statistical analysis of costs The costs were presented as mean values plus or minus (+/-) the standard deviation. An analysis of variance was used to test the statistical significance of differences in the estimated quantities of resources used and costs.
Indirect Costs The indirect costs were not included in the economic evaluation.
Sensitivity analysis Univariate sensitivity analyses were carried out to test the robustness of the cost results to variations in prices and study samples (intention to treat and treatment completers only). Ranges for the costs were derived from 95% percentiles.
Estimated benefits used in the economic analysis See the 'Effectiveness Results' section.
Cost results Study medications costs (per patient) were statistically lower for ATO compared with LOV and PRA, (p<0.01), but were similar to those associated with FLU and SIM. The costs of related adverse events were similar among the five strategies.
The costs associated with treatment visits were statistically lower for ATO compared with the other statins, (p<0.01).
The total costs per patient were $683.37 (+/- 501.30) with ATO, $894.72 (+/- 447.94) with FLU, $1,291.33 (+/- 920.94) with LOV, $1,107.97 (+/- 716.29) with PRA and $779.10 (+/- 522.65) with SIM.
The costs of ATO were significantly lower than the costs associated with the other statins, (p<0.01). The cost-savings with ATO ranged from $95 (versus SIM) to $608 (versus LOV).
Alternative scenarios that were considered in the sensitivity analysis did not alter the cost-advantage of ATO.
Synthesis of costs and benefits A synthesis of the costs and benefits was not carried out because ATO dominated the remaining medications. In effect, ATO was both more effective and less costly.
Authors' conclusions Atorvastatin (ATO) was the most cost-effective medication for the treatment of patients with hypercholesterolaemia in the USA. ATO dominated other currently marketed medications including fluvastatin (FLU), lovastatin (LOV), pravastatin (PRA) and simvastatin (SIM).
CRD COMMENTARY - Selection of comparators The selection of the comparators was appropriate because the five statin regimens reflected widely used medications for the treatment of hypercholesterolaemia. The doses were clearly reported. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness The effectiveness evidence came from a clinical trial, which was appropriate for the study question. The information on the design and results of the study was limited, but the randomised design, the baseline comparability of the study groups, the use of entire randomised sample, and the multi-centre design enhanced the validity of the study. In addition a very large sample size was used. The length of follow-up was appropriate.
Validity of estimate of measure of benefit The summary benefit measure was specific to the disease considered in the study and is not comparable with the benefits of other health care interventions. The use of NCEP-II LDL-C targets represents an intermediate measure of the impact of the study medications on patient health.
Validity of estimate of costs The authors stated explicitly which perspective was adopted in the study. As such, all the relevant categories of costs were included in the analysis. However, the inclusion of other non-medical direct costs would have been interesting. Extensive information on resource use and unit costs was provided. In addition, a detailed breakdown of the items was given, which enhances the possibility of replicating the study. The source of the data was reported. The costs were treated stochastically and cost estimates were varied in the sensitivity analysis. The price year was reported, which aids reflation exercises in other settings.
Other issues The authors reported the findings from other published studies, which were consistent with the results of the current analysis. The issue of the generalisability of the study results to other settings was partially addressed in the sensitivity analyses, where alternative prices were considered. The study referred to patients requiring treatment for hypercholesterolaemia and this was reflected in the authors' conclusions.
Implications of the study The study results supported the use of ATO for the treatment of patients with hypercholesterolaemia. The authors noted that future studies should examine the impact of introducing generic products on the costs of statins.
Source of funding Funded by Pfizer Inc., New York (NY), USA.
Bibliographic details Smith D G, McBurney C R. An economic analysis of the Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS) PharmacoEconomics 2003; 21(Supplement 1): 13-23 Other publications of related interest Andrews TC, Ballantyne CM, Hsia JA, et al. Achieving and maintaining National Cholesterol Education Program low-density lipoprotein cholesterol goals with five statins. American Journal of Medicine 2001;111:185-91.
Koren MJ, Smith DG, Hunninghake DB, et al. The cost of reaching the National Cholesterol Education Program (NCEP) goals in hypercholesterolaemic patients: a comparison of atorvastatin, simvastatin, lavastatin and fluvastatin. Pharmacoeconomics 1998;14:59-70.
Smith DG, Leslie SJ, Szucs TD, et al. Cost of treating to a modified European Atherosclerosis Society LDL-C target: comparison of atorvastatin versus fluvastatin, pravastatin and simvastatin. Clinical Drug Investigation 1999;17:185-93.
Indexing Status Subject indexing assigned by NLM MeSH Adult; Aged; Atorvastatin Calcium; Cholesterol, LDL /blood; Dose-Response Relationship, Drug; Fatty Acids, Monounsaturated /economics /therapeutic use; Female; Heptanoic Acids /economics /therapeutic use; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors /economics /therapeutic use; Hypercholesterolemia /drug therapy /economics; Indoles /economics /therapeutic use; Lovastatin /economics /therapeutic use; Male; Middle Aged; Pravastatin /economics /therapeutic use; Pyrroles /economics /therapeutic use; Risk Factors; Simvastatin /economics /therapeutic use; Treatment Outcome AccessionNumber 22003008090 Date bibliographic record published 30/06/2005 Date abstract record published 30/06/2005 |
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