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Once daily ceftriaxone plus amikacin vs three times daily ceftazidime plus amikacin for treatment of febrile neutropenic children with cancer |
Charnas R, Luthi A R, Ruch W |
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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 Antimicrobial treatments for febrile neutropenic children with cancer:
(a) once daily ceftriaxone plus amikacin and,
(b) three times daily ceftazidime plus amikacin.
Economic study type Cost-effectiveness analysis.
Study population Febrile neutropenic children with leukaemia, lymphoma or solid tumours after chemotherapy, aged between 1 and 17 years.
Setting Hospital. The economic study was carried out in the USA
Dates to which data relate Data were collected for the effectiveness and resource use analyses during the period March 1990 to March 1992.1993 prices were used
Source of effectiveness data The evidence for final outcomes was derived from a single study.
Link between effectiveness and cost data The costing was undertaken retrospectively and not on the same patient sample as that used in the effectiveness study; cost estimates were performed for the USA (although it was not a participating country in the trial).
Study sample Eligible patients were febrile neutropenic children with leukaemia, lymphoma or solid tumours after chemotherapy. A target sample size of 190 patient episodes per treatment group was required based on an estimated response rate of 70% with the three times daily regimen and Alpha = 0.10 for a one-tailed test and Beta = 0.20 (power 80%).468 patient episodes were included in the study; 104 episodes were excluded from analysis (51 from the ceftriaxone+amikacin arm and 53 from the ceftazidime plus amikacin arm). For the final analysis there were 181 patient episodes in the ceftriaxone+amikacin arm and 183 episodes in the ceftazidime+amikacin arm.
Study design The study was an open, prospective, randomised, comparative multicentre study, involving 17 centres in 8 countries. Patients were followed up for at least 4 days after discontinuation of treatment.
Analysis of effectiveness The analysis of the clinical study was based ontreatment completers only. Outcome was evaluated by the investigator at the end of treatment. Outcome was classified as 'complete response', 'improvement' or 'failure'. 'Complete response' was defined as the resolution of all signs and symptoms of infection, pathogen eradication and apyrexia for more than 4 days after discontinuation of the study antibiotics, with no change in the allocated antibiotic therapy. 'Improvement' was defined as resolution of fever with lessening of the signs and symptoms of the infection, but without fully meeting the criteria of either complete response or failure. 'Failure' was defined as a lack of improvement, deterioration or the requirement for a change in antibacterial regimen. Groups were showed to be similar in terms of sex, age, weight, race, neutropenia, frequency of antimicrobial prophylaxis or underlying disease (with the exception of acute lymphatic and nonlymphatic leukaemia).
Effectiveness results Analysis of response showed largely similar rates of complete response between the two groups in all three categories of infection (microbiologically proved; clinically documented; and fever of unknown origin). Overall complete response rates in both the ceftriaxone plus amikacin group and the ceftazidime plus amikacin group were 66%. Overall a further 4% of ceftriaxone+amikacin patients improved and 30% were treatment failures. In the ceftazidime+amikacin group a further 5% improved and 29% were failures. There were five deaths in the ceftriaxone plus amikacin group, two of which were caused by infection and three by the underlying disease. Of the four deaths in the ceftazidime plus amikacin group, one was caused by septic shock and the remaining three by underlying disease. The number of patients with treatment-related adverse events and laboratory toxicity were similar in both groups, in particular with low frequencies of nephro- and oto-toxicity.
Clinical conclusions These results demonstrate that once daily ceftriaxone plus amikacin was as effective as multiple daily dosing with ceftazidime plus amikacin, the standard treatment of febrile neutropenic patients with cancer.
Measure of benefits used in the economic analysis No summary benefit measure was identified in the economic analysis and only separate outcomes were reported.
Direct costs Costs did not need to be discounted. Quantities were not reported separately. Only health services costs were considered. Some costs were reported separately. Acquisition costs were based on 1993 average wholesale prices of multiple dose vials. Daily drug delivery costs were calculated from values published elsewhere, assigning monetary values for pharmacy equipment, pharmacist, starting intravenous therapy, equipment for starting intravenous therapy, nursing time, intravenous administration equipment, antibiotic level, detection of side effects and costs of side effects. Estimated daily hospitalisation costs were based on the average daily hospitalisation cost from one US centre. Data were collected for the resource use analyses during the period March 1990 to March 1992. 1993 prices were used.
Sensitivity analysis No sensitivity analysis was performed.
Estimated benefits used in the economic analysis Cost results The total daily cost of once daily ceftriaxone plus amikacin was $162 versus $244 for three times daily ceftazidime plus amikacin.
Synthesis of costs and benefits Authors' conclusions The authors concluded that once daily administration of ceftriaxone plus amikacin was as safe and effective as three times daily administration of ceftazidime plus amikacin in the treatment of febrile neutropenic children and was more cost-effective.
CRD COMMENTARY - Selection of comparators A justification was given for the comparators used: the combination of ceftazidime and amikacin is widely used for treatment of febrile neutropenic patients. You, as a database user, should consider if this applies to your own setting.
Validity of estimate of measure of benefit The estimate of the measure of benefit used in the economic analysis is likely to be internally valid.
Validity of estimate of costs Not all resource quantities were reported separately from prices, and costs were calculated from US cost data although the US was not a participant in the trial.
Other issues As the study lacked statistical and sensitivity analyses, the results should be treated with some caution.
Source of funding Supported by Hoffman-La Roche Ltd, Basel Switzerland.
Bibliographic details Charnas R, Luthi A R, Ruch W. Once daily ceftriaxone plus amikacin vs three times daily ceftazidime plus amikacin for treatment of febrile neutropenic children with cancer. Pediatric Infectious Disease Journal 1997; 16(4): 346-353 Indexing Status Subject indexing assigned by NLM MeSH Adolescent; Amikacin /administration & Anti-Bacterial Agents /administration & Ceftriaxone /administration & Cephalosporins /administration & Child; Child, Preschool; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Fever /etiology; Gram-Negative Bacteria /drug effects; Gram-Positive Bacteria /drug effects; Humans; Infant; Leukemia /complications; Lymphoma /complications; Male; Microbial Sensitivity Tests; Neoplasms /complications /drug therapy; Neutropenia /chemically induced /drug therapy; dosage /adverse effects; dosage /adverse effects; dosage /adverse effects; dosage /adverse effects AccessionNumber 21997000591 Date bibliographic record published 28/02/1999 Date abstract record published 28/02/1999 |
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