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Cost-effectiveness of epoetin and autologous blood donation in reducing allogeneic blood transfusions in coronary artery bypass graft surgery |
Marchetti M, Barosi G |
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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 Four strategies were compared alongside coronary artery bypass graft (CABG) surgery: preoperative epoetin alone; autologous blood donation (ABD) alone; ABD with epoetin support; and no ABD or epoetin.
Study population A hypothetical cohort of 67 year old men undergoing CABG. The inclusion criteria were based on an experimental protocol proposed by Kyo et al (1992). The authors did not provide any additional details about health status, such as duration and severity of disease or co-morbidity.
Setting The setting was secondary care. The authors do not report that the economic analysis was carried out in Italy.
Dates to which data relate Effectiveness data were derived from sources published between 1990 and 1999. Cost data were from sources published between 1993 and 1999. Prices were standardised to the present year, which is assumed to have been 1999 (the year the article was submitted for publication).
Source of effectiveness data Effectiveness data were derived from a review of published studies.
Link between effectiveness and cost data The model analysed outcomes alongside costs. Using these, it combined the outcomes and costs by calculating the ratio of the additional cost to the additional survival for each intervention strategy relative to the "neither" strategy.
Modelling A decision tree was used to model the costs and benefits of the four proposed strategies.
Effectiveness-related variables were incorporated into the model. Those effectiveness variables relating to quality-adjusted life expectancies and transfusion complications were adjusted to the model's shorter time span by means of the Declining Exponential Approximation of Life Expectancy (DEALE) approach.
The model was built using the software package DATA 3.5 for Windows (Treeage Software).
Outcomes assessed in the review A range of outcome measures was identified and used in the model. The primary measure was quality-adjusted life years (QALYs). Other important measures included perioperative mortality and HIV, HBC and HCV related life expectancy and associated quality-adjusted life expectancy, the effectiveness of epoetin and combined therapy, CABG survival and QALY, acute haemolytic and non-haemolytic reactions rates and mortality, short-term health conditions such as acute hepatitis, quality adjustments, and transfusion complication effects on quality-adjusted life expectancies.
Study designs and other criteria for inclusion in the review Randomised control trials, meta-analyses, longitudinal, observational, and cost-effectiveness models were identified in the review. The authors did not report the inclusion and exclusion criteria.
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 20 references were quoted as sources of effectiveness data. The authors did not state how many of these references were primary studies.
Methods of combining primary studies Point estimates were taken from one paper for each effectiveness measure. Other related papers were used to obtain ranges for sensitivity analyses.
Investigation of differences between primary studies The authors did not investigate differences between studies.
Results of the review The authors reported all point estimates and ranges for sensitivity analyses in the paper. The main results were as follows.
Perioperative mortality in CABG surgery: 2.7% (range: 2 - 4%).
Allogeneic blood transfusion rate: 57% (range: 35 - 92%).
Efficacy of epoetin and ABD: 72% (range: 50 - 80%).
Efficacy of epoetin: 33% (range: 10 - 75%).
Efficacy of ABD: 72% (range: 3 0 - 60%).
Discounted life expectancy for CABG survivor: 11.76 years (7.46 QALYs).
Quality adjustments for short-term state of acute hepatitis: 2 weeks (range: 1 - 3)
Quality adjustments for short-term state of myelopathy: 30 weeks (range: 10 - 40)
Measure of benefits used in the economic analysis The measure of benefit adopted was quality-adjusted life years (QALYs). The values for QALYs were taken from published studies. The methods used to obtain valuations of the health states from the interventions were not reported in the paper.
Direct costs Resource quantities and costs were not reported separately. All costs were discounted at 5% per annum. Costs were taken from a range of studies published between 1993 and 1999 and were standardised to the then current year (1998) by using a 5% per annum inflation rate. The authors did not state whether the costs used were average, marginal or incremental.
The cost per unit of allogeneic blood was taken from a 1998 costing paper and included the cost of blood collection and processing, infectious disease testing, inventory management, compatibility testing and indirect costs (which were not stated).
The baseline cost of epoetin and its associated pharmacy expenses and administration was based on 10 administrations over a four week period. The cost of the drug itself was based on the cost to Italian hospitals.
The cost of epoetin with ABD was $1,890.
Estimated lifelong costs incurred by society for the care of chronically infected HCV and HBV patients were estimated from published Markov studies.
The cost of a myocardial infarction was taken from a study looking at the hospital cost for patients aged 65 and over in 1998.
The overall cost of HIV infection was from a 1993 cost-effectiveness paper.
Statistical analysis of costs Deterministic, point estimate costs were used and sensitivity analysis was performed on a stated range for each cost.
Indirect Costs Indirect costs were not stated. No reason was given by the author for their exclusion.
Currency US dollars ($). It appears that some costs may have been converted from other currencies (e.g. Italian lira), although this was not stated and conversion rates were not quoted.
Sensitivity analysis Sensitivity analysis was performed on all the effectiveness variables, except the actual QALY values used for given health states. The ranges tended to be based around estimates reported in the literature, in particular those reported in RCTs and meta-analyses.
A best case and worst case scenario was also modelled based on 50 year old patients and 80 year old patients respectively.
Analysis of extremes was used to estimate the effect of a best case and worst case scenario.
A scenario analysis was also performed in which postoperative infections were included.
Costs were also subjected to sensitivity analysis.
Estimated benefits used in the economic analysis All outcomes were discounted at 5% per annum. On average, quality-adjusted life expectancy was 7.31 for patients in the four strategies in the baseline analysis. The results from the baseline analysis are shown below.
Life expectancy (QALY) for each strategy was:
epoetin and ABD, 7.310686;
epoetin alone, 7.310626;
ABD alone, 7.310633 and
none, 7.310633.
Incremental effectiveness (QALY) results for each strategy relative to none were:
epoetin and ABD, 0.000146;
epoetin alone, 0.000086 and
ABD alone, 0.000093;
Cost results All costs presented included a discount rate of 5% per annum. Costs of adverse effects were included. The duration of the intervention and comparator quantities was not reported.
The total cost of each strategy was:
epoetin and ABD, $1,359;
epoetin alone, $1,189;
ABD alone, $687 and
none, $521.
The incremental costs for each strategy relative to none were:
epoetin and ABD, $838; epoetin alone, $668 and
ABD alone, $166.
Synthesis of costs and benefits The costs and outcomes were combined through the incremental cost per QALY, relative to a no drug strategy. In 1998 prices the authors estimated the following incremental ratios:
epoetin and ABD, $5,739,726;
epoetin alone, $7,767,441 and
ABD alone, $1,784,946.
The authors also reported the results of the scenario where postoperative complications were included in the model. This showed that the cost-effectiveness of the drugs was particularly sensitive to the inclusion of postoperative complications. It became cost effective to use epoetin and ABD, and ABD alone (the dominant strategies). Epoetin alone produced an incremental cost per QALY of $6,288.
The other most sensitive parameters were adverse effects of epoetin and ABD, and the clinical scenarios, such as the age of the patient. In the best case scenario (50 year old male), which had higher efficacy rates of drugs, longer life expectancy and higher cost of caring for patients chronically affected by blood-borne viruses, all drug strategies were dominant in terms of cost-effectiveness. For the worst case scenario (80-year-old male) none of the drug strategies were cost-effective. This scenario had lower drug efficacy, lower life expectancy and lower cost of care for patients with chronically affected blood-borne viruses.
The authors also reported that the cost per transfusion avoided by using epoetin was $1,095.
Authors' conclusions Epoetin with ABD was more cost-effective than ABD alone, but neither were more cost-effective than a do nothing strategy. Based on current knowledge, it is not cost-effective to use epoetin or ABD before CABG as a blood saving policy.
CRD COMMENTARY - Selection of comparators The authors justified their selection of comparators used within the model. Through these choices and best-case and worst-case scenario analysis, a range of clinical practices was covered, which may include those in your own setting.
Validity of estimate of measure of benefit The authors did not state the method used to identify the literature sources, nor did they comment on the quality of the studies used. Furthermore, some of the studies used were published ten years previously, in particular CABG survival data was so derived. It may be the case that CABG surgery effectiveness had improved during the intervening decade.
The authors used point estimates from a single randomised controlled trial (RCT) for the effectiveness of the drugs, instead of the estimate derived from a meta-analysis. Although the results from the meta-analysis were incorporated into the sensitivity analysis, they may have provided a better estimate of the true effectiveness of epoetin in the baseline model. Consequently, data were selectively chosen by the authors.
The use of RCTs is preferable to observational and longitudinal studies. It was not stated whether alternative RCT results were available when effectiveness data was taken from observational or longitudinal studies.
The primary outcome measure was quality-adjusted life years and this was obtained directly from the effectiveness analysis calculated by the model. However, although the authors stated the source of the values, they did not state how these values were derived. They did not describe the technique used, nor from whose opinions or judgements values were derived. This limits the generalisability of the results to other settings, patient groups and years. A 5% discount rate per annum was applied to all outcomes. Undiscounted results were not reported. The discount rate was not varied in the sensitivity analysis and the results should therefore be interpreted with caution if other health care settings use different discount rates.
Validity of estimate of costs The perspective of the study was not stated which limits the applicability of the results to other countries. Indirect costs were not incorporated which suggests that the perspective was that of the health service. In the baseline analysis the patient was assumed to be 67 years old, and as a consequence it is likely that lost work days for this group would be minimal and the authors' conclusions are unlikely to be affected. However, for the best case scenario (patients aged 50) such lost days may have been significant.
Costs were based on published studies. They were converted into 1998 prices using a stated inflation rate and a sensitivity analysis around these costs was performed. Quantities of resources were suggested in the model by the inputs. These may or may not reflect actual quantities used. If they do not reflect actual quantities this may limit the generalisability of the results to other settings. Health care decision makers may therefore be unable to apply their own costing.
The number of countries from which prices were taken is not clear. In particular, the cost of epoetin was from an Italian hospital, as, it seems, was the cost of administering it. Although no conversion rates were stated, the authors did describe the assumptions behind the total cost of the drug.
A 5% discount rate per annum was applied to all costs. Undiscounted results were not reported. The discount rate was not varied in the sensitivity analysis and so the results should be interpreted with caution if other health care settings use different discount rates. It was not clear from the paper what time span the model covered, as the outcomes reported were quality-adjusted life years and not actual life years. This would be equivalent if the quality of life during each year of life after CABG surgery was one, which is extremely unlikely.
Other issues The authors stated that no other studies have looked at the cost-effectiveness of epoetin in a cardiac setting, although they compared the cost per QALY ratio of using epoetin with other health technologies. They acknowledged that current knowledge and data were presently limited and that the results of the model could change over time as more data became available.
The authors' conclusion of non cost-effectiveness was for the baseline, 67 year old male patient. They did not state whether this would be the same for female patients. For younger patients, epoetin may be more cost-effective.
Implications of the study The authors did not recommend the use of epoetin as a blood saving policy during CABG surgery as it was not cost-effective. Health care decision makers should look at the costs of blood units, epoetin and ABD to determine whether they differ significantly from those reported in the study. The study implicitly assumed that major cost drivers, such as length of stay, would remain the same between patients going down the different strategies. Decision makers should be aware of whether this is true within their own setting. The impact of using epoetin on quality of life and life expectancy was minimal compared to a do nothing strategy.
Bibliographic details Marchetti M, Barosi G. Cost-effectiveness of epoetin and autologous blood donation in reducing allogeneic blood transfusions in coronary artery bypass graft surgery. Transfusion 2000; 40(6): 673-681 Other publications of related interest Kyo S, Omoto R, Hirashima K et al. Effect of human recombinant erythropoietin on reduction of homologous blood transfusion in open-heart surgery. A Japanese multicentre study. Circulation 1992;86:II413-II418.
Indexing Status Subject indexing assigned by NLM MeSH Aged; Blood Loss, Surgical; Blood Transfusion /adverse effects /economics /statistics & Blood Transfusion, Autologous /economics; Computer Simulation; Coronary Artery Bypass /economics /mortality; Cost-Benefit Analysis; Decision Trees; Drug Costs; Erythropoietin /administration & Feasibility Studies; Health Care Costs; Humans; Male; Models, Theoretical; Preoperative Care /economics; Recombinant Proteins /administration & Safety; Virus Diseases /economics /transmission; dosage /economics /pharmacology; dosage /economics /pharmacology; numerical data AccessionNumber 22000001074 Date bibliographic record published 31/07/2001 Date abstract record published 31/07/2001 |
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