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Economic analysis of fluconazole versus amphotericin B for the treatment of candidemia in non-neutropenic patients |
Dranitsaris G, Phillips P, Rotstein C, Puodziunas A, Shafran S, Garber G, Smaill F, Salit I, Miller M, Williams K, Conly J, Singer J, Ioannou S |
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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 Treatment of candidemia using two intravenous antifungal therapies, either fluconazole (FLU) or amphotericin B(AMB).
Economic study type Cost-effectiveness analysis.
Study population Non-neutropenic adult patients with candidemia, who had at least 1 blood culture which tested positive for yeast species, and a neutrophil count of greater than 500 per mm3.
Setting Hospital. The economic study was carried out in Ontario, Canada.
Dates to which data relate The effectiveness and resource use data were obtained from a clinical trial the results of which were published in 1997. 1997 prices were used.
Source of effectiveness data The evidence for the final outcomes was derived from a single study.
Link between effectiveness and cost data The costing was retrospectively undertaken on the same patient sample as that used in the effectiveness study.
Study sample Any power calculations to determine the sample size were not reported. The study sample consisted of 106 patients randomised to the FLU group (n=52) with a median age of 65 (range: 21 - 86) years or the AMB group (n=53) with a median age of 65 (range: 21 - 86) years.
Study design The study was a multicentre randomized controlled trial. The treatment cohort was followed up for 6 months. The analysis of efficacy was based on 50 patients in the FLU group (rather than n=52). Patients were stratified using the Apache II score and randomized on a one-to-one basis to treatment with AMB or FLU.
Analysis of effectiveness The principle used in the analysis of effectiveness was reported to be intention to treat. The primary health outcome was the percentage of patients obtaining successful resolution of signs and symptoms of infection. The main adverse effect was related to the kidneys (serum creatinine). Groups were shown to be comparable in terms of age, sex and prognostic features. Adjustment for confounding variables was not stated.
Effectiveness results 31 out of 53 patients (58%) treated with AMB showed a successful resolution of signs and symptoms of infection compared with 25 out of 50 patients (50%) treated with FLU, (p=0.39, 95% CI of the difference -8 - 24%). Drug-induced adverse effects related to the kidneys were present: 43% of patients treated with AMB and 19% of patients treated with FLU had a creatinine level greater than or equal to 1.5 times the baseline-level, (p=0.014).
Clinical conclusions With the statistically similar efficacy, the use of FLU was associated with significantly less drug-induced adverse effects.
Measure of benefits used in the economic analysis No summary benefit measure was identified in the economic study, and only separate clinical outcomes were reported.
Direct costs Costs were not discounted due to the short time period involved. Quantities and costs were not fully reported separately. The source of quantity/cost was the patients' hospital records. Hospital costs included were the costs for primary and secondary intravenous therapy (including premedication) with either AMB or FLU, laboratory tests, patient clinical monitoring and adverse effects management. The perspective adopted in the cost analysis was that of the hospital. 1997 price data were used.
Statistical analysis of costs A Mann-Whitney U test was carried out to compare the study groups in terms of costs. A multivariate analysis was performed treating the cost as a dependent variable.
Currency Canadian dollars (Can$).(Can$1= $US 0.75 in June 1997).
Sensitivity analysis The sensitivity analysis was carried out varying: the therapy duration (all FLU doses IV and Oral FLU step-down at 7 days), the Oral IV FLU step down therapy (three, seven and ten days), and the adverse effect costs (AMB adverse effect costs Can$512 (as per Kahn) and the increasing adverse effect costs 5-fold: $Can795).
Estimated benefits used in the economic analysis Cost results The treatment costs per patient using AMB were Can$2,370 (SD, 1,112) and using FLU were Can$3,578 (SD, 2,200), (p=0.001).
Synthesis of costs and benefits The benefits and costs were not combined. An incremental analysis was not performed.
Authors' conclusions The results suggest that the FLU administration regimen used in the Canadian randomised trial for the treatment of candidemia in non-neutropenic patients may result in increased hospital costs compared with AMB. However, comparable expenditures could be realised if FLU is administered intravenously for the first 7 days and then orally in patients whose condition allows for reliable oral therapy.
CRD COMMENTARY - Selection of comparators The choice of the comparator was clearly justified. It was regarded as the drug of choice in the context in question. You, as a database user, should consider whether this is a widely used health technology in your own setting.
Validity of estimate of measure of benefit The internal validity of the effectiveness results is likely given the use of a randomised design. In view of the lack of an explicit summary benefit measure, the study may be regarded as a cost-consequences analysis.
Validity of estimate of costs The quantities were not fully reported separately from the costs. However, adequate details of methods of cost estimation were given.
Other issues The authors pointed out that the economic results may not be generalisable to other settings or countries, as the hospital resources used by patients were protocol-driven, and because of the lack of hospital duration data and other weaknesses.
Source of funding Supported by a grant from Pfizer Canada Inc.
Bibliographic details Dranitsaris G, Phillips P, Rotstein C, Puodziunas A, Shafran S, Garber G, Smaill F, Salit I, Miller M, Williams K, Conly J, Singer J, Ioannou S. Economic analysis of fluconazole versus amphotericin B for the treatment of candidemia in non-neutropenic patients. PharmacoEconomics 1998; 13(5 Part 1): 510-518 Indexing Status Subject indexing assigned by NLM MeSH Adult; Aged; Amphotericin B /therapeutic use; Antifungal Agents /therapeutic use; Candidiasis /drug therapy; Comparative Study; Female; Fluconazole /therapeutic use; Fungemia /drug therapy; Health Care Costs; Humans; Male; Middle Aged; Research Support, Non-U.S. Gov't AccessionNumber 21998008139 Date bibliographic record published 29/02/2000 Date abstract record published 29/02/2000 |
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