|
Cost-utility of enoxaparin compared with unfractionated heparin in unstable coronary artery disease |
Nicholson T, McGuire A, Milne R |
|
|
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 Enoxaparin was compared with unfractionated heparin (UFH) for the short-term treatment of unstable coronary artery disease (CAD).
Study population The target population for the model comprised patients with unstable angina and non-Q-wave myocardial infarction, often referred to as unstable CAD or acute coronary syndromes.
Setting The setting was tertiary care. The economic study was carried out in the UK.
Dates to which data relate The effectiveness evidence was taken from 1994 to 1998 (See Supplement Two in 'Other Publications of Related Interest'). The health service use costs were taken from 1995 and 1996. The price year was 1998.
Source of effectiveness data The effectiveness data were derived from completed studies.
Modelling A model was constructed to derive the composite health outcome measure used. Survival analysis techniques (actuarial method) were used. The authors provided a link to additional information about the methods used (Supplement Two, see 'Other Publications of Related Interest').
Outcomes assessed in the review The primary composite outcome was death, myocardial infarction or recurrent angina.
Study designs and other criteria for inclusion in the review A model was constructed to derive the composite health outcome measure used. Survival analysis techniques (actuarial method) were used. The authors provided a link to additional information about the methods used (Supplement Two, see 'Other Publications of Related Interest').
Sources searched to identify primary studies The sources searched were the Cochrane Library, CRD databases (DARE, HTA, NHS EED), GEARS (Getting Easier Access to Reviews), Best Evidence 3, MEDLINE, PreMEDLINE, EMBASE, BIOSIS Previews, the Science Citation Index, EconLit, the National Research Register, and the meta Register of Controlled Trials. Full details of the searches, inclusion criteria, appraisal and data extraction methods, and tables of results were provided as additional material.
Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data The authors applied the inclusion criteria, extracted data and undertook a critical appraisal of identified studies using the CRD checklist. In addition, the papers were scored for quality using the Jadad instrument. A second reviewer was consulted where there was uncertainty.
Number of primary studies included Three primary studies appear to have been included in the review of effectiveness, although the main outcomes were taken from two large double-blind trials and their meta-analyses.
Methods of combining primary studies Not reported. See Rawles et al 1992.
Investigation of differences between primary studies Results of the review For the mean event-free years, values were used in series, and not individually, for each outcome.
The results for the base-case and ranges of efficacy were as follows:
the life-years gained were 0.010 in the base-case (range: 0.002 - 0.010);
the myocardial infarction free time gained was 0.007 in the base-case (range: 0.008 - 0.013); and
the time free from recurrent angina was 0.018 in the base-case (range: 0.014 - 0.022).
Methods used to derive estimates of effectiveness This analysis was based on published data and authors' assumptions.
Estimates of effectiveness and key assumptions To quantify the benefits from treatment, the authors used the individual components of a composite outcome although the latter were not statistically significant. The base-case used the first trial's most severe event rates to one year. The authors estimated the mean event free times gained for deaths, myocardial infarctions and recurrent angina, using survival analysis techniques (actuarial method) to estimate the area between the survival curves.
Measure of benefits used in the economic analysis The measure of benefits used was the quality-adjusted life-years (QALYs). The health states of myocardial infarction and unstable angina were valued using a modified Rosser-Kind matrix, with one study used as the main source (Rawles et al. 1992). To quantify the QALY change associated with treatment, the authors combined the mean absolute risk reduction for each event with the associated quality of life change. The authors stated that the current study excluded the disutility associated with undergoing percutaneous transluminal coronary angioplasty or coronary artery bypass grafting (CABG) because revascularisation rates were likely to be low at the time of the quality of life study. Hence, they were not included in these results. Full details of the methods for estimating QALYs, health states and health-related quality of life associated with cardiac events were included as additional material.
Direct costs The direct costs included treatment-related costs, nursing time, intravenous pumps, drugs, drug administration and consumables. The authors assumed that the cost per day for the length of stay covered resource use for adverse events such as haemorrhage.
The quantities and the costs were estimated from published data and authors' assumptions. To ensure generalisability within the UK, the authors used national costs supplemented by local costs (or resource use information) where necessary. Outpatient follow-up, ambulance transport and non-NHS costs were excluded. Where required, the treatment costs of myocardial infarction and recurrent angina were based on resource use of the most severe event at one year from one trial for the base-case, and of all events for the upper value. Since data were only modelled for one year, discounting was unnecessary. The unit costs were obtained for 1995/96 and were then increased to 1998 prices using inflation indices from the Public Expenditure Survey Team at the Department of Health, Leeds, (i.e. allowing for inflation, but not technological changes). The price year was 1998. Full details of the valuation of treatment-related costs and savings, and average and minimum or maximum values used in the base-case and sensitivity analyses were provided in an appendix.
Statistical analysis of costs No statistical analysis of the costs was reported.
Indirect Costs The indirect costs were not included.
Sensitivity analysis One-way sensitivity analyses were performed to determine how robust the estimates were to the assumptions. The ranges were derived from published literature and authors' assumptions. Other scenario analyses used all events to evaluate the outcomes, or the second trial's results (assuming event rates at 43 days) were maintained to one year, as in the first trial. Full details were provided in an appendix. The authors used the following three scenarios for the analysis.
Scenario 1 (base-case): difference in treatment-related costs minus potential savings (from revascularisations (CABG and angioplasty) and length of stay).
Scenario 2: as for scenario 1, but including value added tax (VAT) at 17.5%, National Insurance and superannuation (i.e. transfer payments) since the NHS must pay these.
Scenario 3: as for scenario 1, but including the treatment costs of cardiac events (myocardial infarctions and recurrent angina) instead of differences in length of stay.
The unit costs for length of stay should be interpreted with caution on account of somewhat arbitrary accounting. This scenario was used to determine whether the alternative approach (treatment of cardiac events) produced much difference.
Estimated benefits used in the economic analysis For the quality of life data, the values were used in series, and not individually, for each outcome. The quality of life change associated with death was 0.977 in the base-case and for the lower value; there was no upper value. The base-case for myocardial infarction (Q-wave) was 0.160 and the lower value was 0.102; there was no upper value. For no-Q-wave myocardial infarction, the base-case was 0.088 and the lower value was 0.056; there was no upper value.
Cost results The average daily costs in the base-case, excluding VAT for drugs and administration, were 8.47 for UFH and 12.16 for enoxaparin. Thus, the total treatment costs for the base-case (2.6 days) were 23.02 for UFH and 31.62 for enoxaparin.
The total costs of the two strategies including other resource used were not reported separately (though differences between treatments were reported).
Synthesis of costs and benefits The base-case was associated with a QALY gain of 0.013 and cost-savings of 317 for each person treated with enoxaparin instead of UFH.
There were net cost-savings and QALY gains in all but one case. The latter was due to the longer length of stay for the UK cohort, which resulted in a net cost of 42 and hence a cost per QALY of 3,305. However, there was still a net cost-saving (158) if there was no difference in length of stay between the comparators.
The event free time gained was 0.004 QALYs as the lower value and 0.014 QALYs as the upper value.
The results were robust to changes in treatment duration and related costs, and the unit cost of CABG.
The results were moderately sensitive to changes in the unit cost of angioplasty and were very sensitive to variation in the rates of revascularisation, and the duration and unit cost of length of stay.
Similarly, using differences in treatment costs for myocardial infarctions and recurrent angina instead of the mean length of stay (third scenario) had a large impact on the net cost-savings. Changes in mean event free times reduced the QALY gain by up to three-fold.
Authors' conclusions Moving from unfractionated heparin (UFH) to enoxaparin would appear to be cost-saving and more beneficial in patients with unstable coronary artery disease (CAD), although cost implications depend on local revascularisation practice.
CRD COMMENTARY - Selection of comparators The choice of the comparators was explicitly justified. These heparins were chosen on the basis of the purpose of this study, which was to consider the cost-utility of enoxaparin since decision-makers were facing the choice of substituting the traditional UFH. Other low molecular weight heparins were explicitly excluded. You should judge whether these drugs are relevant in your setting, or whether other comparators from other drug classes could also be relevance.
Validity of estimate of measure of effectiveness The authors used data from published sources only. The main sources of effectiveness evidence were two large double-blind randomised clinical trials and their meta-analyses. According to the authors, this literature was the most comprehensive synthesis of current knowledge in this area and there were no published full economic evaluations of enoxaparin versus UFH, only cost studies.
A systematic review of the literature was undertaken, full details of which were provided in supplements. The effectiveness estimates were derived credibly from primary studies and the authors' own assumptions, and were combined. The authors provided access to the methods used to derive estimates of effectiveness, and justified their assumptions with reference to the medical literature. These estimates were investigated in sensitivity analyses, using ranges from the literature.
Validity of estimate of measure of benefit The authors used QALYs as the measure of benefits. These were derived from a published paper through modelling. This measure of benefit enables comparisons across different health technologies. The methods used in the literature to derive the utility weights were reported. Sensitivity analyses over QALYs were conducted, and the method used to select the ranges was explicitly reported.
Validity of estimate of costs The authors reported that the costs were estimated from a UK NHS perspective. Therefore, the indirect costs were appropriately not included. Although some costs might have been omitted from the analysis, their omission is unlikely to have affected the authors' conclusions since they were common to both therapies. The resource use quantities and prices were taken from published sources, and sensitivity analyses of the quantities were conducted. Again, full details were provided in a supplementary reference.
Other issues The authors made appropriate comparisons of their findings with those of other studies. The issue of generalisability to other settings was explicitly addressed. The authors reported three general limitations common to modelling. One, the potential biases from amalgamation of multiple data sources. Two, the potentially inadequate sensitivity analyses where data variances were unknown. Three, the fact that the external validity (generalisability) might be weak as results used from international randomised controlled trials reflect efficacy rather than effectiveness.
The authors pointed out further limitations of the current study. First, sensitivity analyses for treatment-related costs principally involved variation in the unit costs, as the ranges for resource use were unavailable. Second, the one-way analyses risked missing possible interactions between variables. Third, the extent of certainty around the effectiveness data was unknown and confidence intervals could not be calculated. Fourth, longer term data were also unavailable. Fifth, the quality of life estimates were not derived in an ideal manner as they used the Rosser classification. Finally, there were also limitations to the unit costs used because these were predominantly national costs: a heterogeneous group (NHS hospitals and pay scales, and manufacturers, and published sources) occasionally supplemented by local costs. According to the authors, it is difficult to estimate the impact of this costing approach.
Implications of the study Enoxaparin appears an efficient choice in patients with unstable CAD, though cost implications depend on local revascularisation practices. The authors stated that further research is needed into the extent that potential savings are realisable and the effect of treatment on risk stratified groups as treatment thresholds might be lower with enoxaparin use, thus increasing total spending without necessarily gaining benefit.
The authors also mentioned that this study did not include other licensed low molecular weight heparins and, since it was prepared for NHS decision-makers, it should not be generalised to other health care systems without caution.
Source of funding Funded by the South East Region Research and Development (Development and Evaluation Service).
Bibliographic details Nicholson T, McGuire A, Milne R. Cost-utility of enoxaparin compared with unfractionated heparin in unstable coronary artery disease. BMC Cardiovascular Disorders 2001; 1(2) Other publications of related interest Indexing Status Subject indexing assigned by NLM MeSH Angina, Unstable /drug therapy; Anticoagulants /economics /therapeutic use; Cost-Benefit Analysis; Enoxaparin /economics /therapeutic use; Fibrinolytic Agents /economics /therapeutic use; Humans; Myocardial Infarction /drug therapy; Quality of Life; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic AccessionNumber 22004008981 Date bibliographic record published 31/01/2006 Date abstract record published 31/01/2006 |
|
|
|