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Pharmacoeconomic evaluation of linezolid versus teicoplanin in bacteremia by Gram-positive microorganisms |
Grau S, Mateu de Antonio J, Soto J, Marin Casino M, Salas E |
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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 examined two antibiotics for the treatment of bacteraemia by Gram-positive micro-organisms. One was linezolid, a new oxazolidinone treatment, while the other was teicoplanin, a glycopeptide. Linezolid was administered at a dose of 600 mg/12 hours, intravenously for the first 7 days and then orally for the following 5 days. Teicoplanin was administered at a dose of 400 mg/day intravenously.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised a cohort of adult inpatients with bacteraemia caused by Gram-positive micro-organisms, including wound infections, bacteraemia, skin and soft tissue infections, right-sided endocarditis and pneumonia.
Setting The setting was a hospital. The economic study was carried out in Spain.
Dates to which data relate The effectiveness data and most resource use data were derived from a study published in 2004. The costs referred to 2002, which might also have been the price year.
Source of effectiveness data The effectiveness evidence was derived from a single study.
Link between effectiveness and cost data The costing was partially carried out on the same sample of patients as that included in the effectiveness analysis. However, in practice, some resource use came from that sample of patients while other resource use data were derived from expert opinion.
Study sample A sample of 430 patients was enrolled in the study. There were 215 patients in each arm (linezolid or teicoplanin). All patients were older than 12 years and weighted more than 40 kg. Patient demographics were not reported and no other details were given.
Study design This was a prospective, randomised, open-label, multinational, multi-centred controlled trial. The length of follow-up was 1 year. Details of the loss to follow-up were not reported.
Analysis of effectiveness The analysis of the clinical study was conducted on an intention to treat basis. The primary outcome measures used in the current pharmacoeconomic analysis were therapeutic success (proportion of patients successfully cured clinically of infections with bacteraemia) and rates of adverse events and discontinuation. The authors did not state whether the study groups were comparable at baseline, but it is likely that no differences were found between the two groups given the study design (a randomised controlled trial).
Effectiveness results The rate of therapeutic success in patients with bacteraemia was 88.5% with linezolid and 56.7% with teicoplanin (difference 31.8%; p=0.009).
The rate of adverse events was 56.3% with linezolid and 51.2% with teicoplanin (difference not statistically significant).
The incidence of drug-related adverse events was 30% with linezolid and 17% with teicoplanin, (p=0.002).
The discontinuation rate was 4.7% with linezolid and 3.7% with teicoplanin.
Clinical conclusions The effectiveness evidence suggested that the two treatments had a similar safety profile, but that linezolid was significantly more effective than teicoplanin in terms of therapeutic success.
Modelling A simple pharmacoeconomic model was constructed to combine the costs and benefits of the two alternative strategies. Patients could either receive linezolid or teicoplanin, and could respond or not respond after the first cycle of treatment that lasted 12 days. Patients who did not respond at the end of this period received a rescue antibiotic. In particular, linezolid was used as rescue therapy for patients who failed first-cycle teicoplanin, while quinupristin or dalfopristin was given to those who failed first-cycle linezolid. The time horizon of the analysis was 28 days.
Measure of benefits used in the economic analysis The summary benefit measure was the therapeutic success (proportion of patients successfully cured clinically of infections with bacteraemia). This was derived directly from the effectiveness analysis.
Direct costs The analysis of the costs was carried out form the perspective of the Spanish health care system. It included the costs associated with medications (including drug administration), hospital stay, diagnostic work-up and nurse time. The unit costs were presented for all items, and some information on resource use was provided. The costs were estimated on the basis of data derived from the Spanish Pharmaceutical Association and a Spanish database. Resource use was estimated using data derived from the clinical trial, augmented with the opinions of a local expert panel. Discounting was not relevant as the costs were incurred during a short timeframe. The costs were estimated using 2002 prices.
Statistical analysis of costs The costs were treated deterministically.
Indirect Costs The indirect costs were not considered in the economic evaluation.
Sensitivity analysis A univariate sensitivity analysis was carried out to identify the model inputs with the greatest impact on the cost-effectiveness ratios. Also, to assess the robustness of the base-case results to variations in the cost of hospital stay, use of rescue antibiotics, longer hospital stay because of treatment failure, difference in treatment success, and the inclusion of drug-related adverse events. Alternative values appear to have been fixed by the authors. A first-order Monte Carlo simulation was run to determine confidence intervals (CIs) around the cost-effectiveness ratios.
Estimated benefits used in the economic analysis See the 'Effectiveness Results' section.
Cost results The total costs per patient were EUR 5,557.04 in the linezolid group and EUR 6,327.43 in the teicoplanin group (difference EUR 770.39).
The higher acquisition cost with linezolid was more than offset by the higher costs associated with the therapeutic failure of teicoplanin and the rescue antibiotic therapy.
Synthesis of costs and benefits Average and incremental cost-effectiveness ratios were calculated in order to combine the costs and benefits of the two treatments.
The average cost per successfully treated patient was EUR 6,279.1 (95% CI: 5,960.2 to 6,510.4) with linezolid and EUR 11,159.5 (95% CI: 10,865.2 to 12,647.3) with teicoplanin.
The incremental analysis revealed that linezolid was the dominant option since it was both more effective and less expensive than teicoplanin. The results of the deterministic sensitivity analysis showed that linezolid remained the most efficient treatment.
Authors' conclusions Linezolid was the most cost-effective treatment for the treatment of bacteraemia caused by Gram-positive micro-organisms in adults in Spain.
CRD COMMENTARY - Selection of comparators The authors provided a clear justification for the choice of the comparators. The comparators were appropriate for the study question and the dosages used were reported. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness The effectiveness evidence was derived from a published clinical trial, which was appropriate for the study question. The validity of the clinical data was ensured by several factors, including the randomised design, the use of intention to treat to deal with loss to follow-up, the appropriate length of follow-up, and the multi-centred nature of the study. However, since the trial had been published elsewhere, information on patient demographics, baseline comparability of the study groups, and statistical analyses was not provided in the current paper. The authors stated in their discussion that the two study groups were similar in terms of disease severity. Nevertheless, the use of a clinical trial should have limited the potential impact of selection bias.
Validity of estimate of measure of benefit The summary benefit measure was specific to the disease considered in the study. It would not be comparable with the benefits of other health care interventions. The impact of the interventions on quality of life was not addressed, although it would have further favoured the linezolid arm given the more acceptable administration route for the patients.
Validity of estimate of costs The cost analysis was restricted to a few items that were relevant from the perspective chosen for the study and the short time horizon. The unit costs were reported and were derived from typical Spanish sources. Resource consumption was estimated using the opinions of an expert panel and the authors. Thus, it should have reflected treatment patterns in the authors' setting. Statistical analyses of the costs were not carried out, but some cost estimates were varied in the sensitivity analysis. In addition, a first-order Monte Carlo simulation was run to determine CIs around the cost-effectiveness ratios. The price year was implicitly reported, which will assist any reflation exercises in other settings.
Other issues The authors reported the results from other economic evaluations and clinical trials, although they did not make any direct comparisons with the current results. The issue of the generalisability of the study results to other settings was not explicitly addressed and few sensitivity analyses were carried out. Therefore, caution will be required when extrapolating the results of the study to other settings and different patient populations. The study referred to patients with bacteraemia caused by Gram-positive micro-organisms and this was reflected in the authors' conclusions. The authors pointed out that the cost-effectiveness of linezolid for other indications was not evaluated in the current study.
It should be noted that all of the cost analysis was driven by the assumptions concerning second-line treatment for patients who failed first cycles with teicoplanin or linezolid. In fact, the higher acquisition cost of linezolid was more than offset by the higher costs associated with therapeutic failure of teicoplanin and the rescue antibiotic therapy. However, patients who did not respond to teicoplanin received linezolid as rescue therapy (this being the main cause of higher rescue therapy costs for teicoplanin), while patients who failed first-cycle linezolid received a less expensive antibiotic. It would be interesting to estimate whether the same results would be obtained if the same second-line treatment was used for linezolid or teicoplanin. Otherwise, the results of this study may be biased in favour of linezolid as first-line treatment.
Implications of the study The study results supported the use of linezolid for the treatment of bacteraemia caused by Gram-positive micro-organisms.
Bibliographic details Grau S, Mateu de Antonio J, Soto J, Marin Casino M, Salas E. Pharmacoeconomic evaluation of linezolid versus teicoplanin in bacteremia by Gram-positive microorganisms. Pharmacy World and Science 2005; 27(6): 459-464 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
Wilcox M, Nathwani D, Dryden M. Linexolid compared with teicoplanin for the treatment of suspected or proven Gram-positive infections. J Antimicrob Chemother 2004;53:335-44.
Winken T, Liz Z, Bleat D, et al. Economic evaluation of linezolid, flucoxacillin and vancomycin in the empiric treatment of cellulitis in UK hospitals: a decision analytical model. J Hosp Infect 2001;49 Suppl A:s13-24.
Shorr AF, Susla GM, Kollef MH. Linezolid for treatment of ventilator-associated pneumonia: a cost-effective alternative to vancomycin. Crit Care Med 2004;32:137-43.
Indexing Status Subject indexing assigned by NLM MeSH Acetamides /economics /therapeutic use; Anti-Infective Agents /economics /therapeutic use; Clinical Trials as Topic; Cost-Benefit Analysis; Gram-Positive Bacterial Infections /drug therapy /economics; Hospital Costs; Humans; Linezolid; Models, Economic; Oxazolidinones /economics /therapeutic use; Teicoplanin /economics /therapeutic use AccessionNumber 22006006426 Date bibliographic record published 31/03/2007 Date abstract record published 31/03/2007 |
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