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Pharmacoeconomic evaluation of roxithromycin versus amoxycillin clavulanic acid in a community-acquired lower respiratory tract infection study |
Scott W G, Cooper B C, Scott H M |
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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 Roxithromycin and amoxycillin clavulanic acid for the treatment of lower respiratory tract infections in general practice.
Economic study type Cost-effectiveness analysis.
Study population Patients over 16 years of age with a productive cough and examination signs of LRTI.
Setting 40 General Practices in a community setting in Australia and New Zealand
Dates to which data relate Effectiveness data were derived in the period September 1991 to February 1993. The price date was not stated.
Source of effectiveness data The evidence for effectiveness was based on a single study which was reported elsewhere (see below).
Link between effectiveness and cost data The cost data were collected prospectively alongside the effectiveness study and on the same patient sample.
Study sample A minimum of 230 patients was to be enrolled in the study to ensure that at least 198 patients were available for efficacy analysis. The sample size was calculated on the basis of an 80% power, a 5% risk and a 15% difference between the two test drugs, assuming an expected clinical cure rate of 77% for amoxycillin/clavulanic acid, and 90% for roxithromycin. To be eligible for analysis, patients had to meet inclusion criteria, and to have taken at least 1 dose of the prescribed medication. A total of 242 patients entered the study; 126 were randomized to roxithromycin and 116 to amoxycillin/clavulanic acid.117 patients who had received roxithromycin and 110 who had received amoxycillin/clavulanic acid were evaluable for efficacy on an intention to treat basis.
Study design The study was a randomised controlled trial performed on a multi-centre basis by 40 GPs. Clinical status was assessed 7 days after the start of medication and/or at the completion of the study medication. Patients were randomly allocated to either of the two treatment regimens. Outcomes were assessed by the blinded chief investigator. After randomisation, 7 patients were excluded due to illnesses unsuitable for treatment with antibiotics in the trial and 8 patients were lost to follow-up. 5 patients (4.3%) who had received roxithromycin and 3 patients (2.7%) who had received amoxycillin/clavulanic acid withdrew from therapy early because of clinical failure or the occurrence of adverse events. There was no difference between the groups in terms of sociodemographic or clinical characteristics but more patients randomised to roxithromycin had a proven bacterial infection (p<0.01).
Analysis of effectiveness The analysis of the clinical study was based on intention to treat. The primary health outcome used in the analysis was clinical response as judged by the chief investigators, whose assessments were based on community standard practice.
Effectiveness results In the analysis of patients with proven bacteriological infections treatment success at study end was achieved for 37/41 (90%) patients receiving roxithromycin and 12/13 (92%) patients receiving amoxycillin/clavulanic acid (p>0.05). For all patients, the clinical response at 7 days was significantly better for roxithromycin, with 81/177 (69%) patients achieving a successful response, versus 62/110 (56%) for amoxycillin/clavulanic acid (p=0.05). There was no statistically significant difference in treatment success at the end of the study (91.5% for roxithromycin and 90.0% for amoxycillin/clavulanic acid). Approximately 55% in each group had complete resolution of the signs and symptoms of infection at study end.
Clinical conclusions Roxithromycin appears to be a more appropriate choice than amoxycillin/clavulanic acid for the treatment of LRTI in the community, given its more appropriate in vitro spectrum, efficacy against most common and atypical pathogens, more convenient dosage regimen (twice a day) and superior tolerability profile. 22 adverse events were reported in 18 patients who had received roxithromycin and 23 events in 20 patients who had received amoxycillin/clavulanic acid. Following blinded assessment, 12/122 (9.8%) patients treated with roxithromycin and 19/111 (17.1%) patients treated with amoxycillin/clavulanic acid were considered to have adverse effects probably or possibly related to the antibiotic (p=0.12). The majority of events for both regimens were gastrointestinal (nausea of diarrhoea).
Measure of benefits used in the economic analysis Clinical success was used as the outcome measure in the economic analysis.
Direct costs Primary medicine costs were obtained by combining the average treatment duration, the average daily dose and the listed price per unit of the medicine. Additional support medicine costs, additional general practitioner consultations and additional diagnostic tests required in excess of the study protocol were included. All prices for additional medicine were generic dispensed prices and cost was calculated by multiplying the dispensed price per unit by the number of units dispensed. GPs used a standardised form to provide data if additional treatments, investigations and consultations were required in cases of treatment failure, treatment withdrawal or adverse effects. Australian prices were applied to the New Zealand data. No price date was reported.
Currency Australian dollars (Aus$). A conversion rate to US dollars for December 1992 was provided (Aus$ 1 = US$ 0.69).
Sensitivity analysis The average treatment duration and dispensed prices for roxithromycin were varied to determine the breakeven point at which the incremental cost savings per clinical success fell to 0.
Estimated benefits used in the economic analysis There was no significant difference in efficacy at study end but the authors calculated an incrementalclinical success as the difference between the success rate of roxithromycin (91.5%) and amoxycillin/clavulanic acid (90.9%).
Cost results The total costs per patient evaluable for treatment were: roxithromycin Aus$ 29.77, amoxycillin/clavulanic acid Aus$ 45.08 (comprising drug costs, visits to GPS, and adverse effects). Patients on roxithromycin required on average 1 day less treatment and fewer extended courses of treatment. The estimated incremental cost savings of using roxithromycin were estimated to be Aus$15.31.
Synthesis of costs and benefits Although authors reported the total incremental net benefit per clinical success (Aus$17.04), combining costs and benefits is not appropriate if there is no demonstrated difference in effectiveness between alternatives or if one of the alternatives is both less costly and more effective. If the average treatment time for roxithromycin was increased by 6.5 days or, if the price per roxithromycin tablet rose by 79%, then the incremental benefit per clinical success would fall to zero.
Authors' conclusions The cost-benefit per clinical success was Aus$17.04. By substituting roxithromycin for amoxycillin/clavulanic acid, Australia would save Aus$1.704 million per 100,000 episodes of LRTI. The results demonstrated that savings in direct costs can be achieved by substituting roxithromycin for amoxycillin/clavulanic acid in the treatment of community-acquired LRTI
CRD COMMENTARY - Selection of comparators Justification was given for the comparators used. Amoxycillin /clavulanic acid (500/125 mg tid) represents one of the standard treatments for LRTI. Roxithromycin (150 mg bid) is the first of a new generation of macrolide antibiotics. You, as a user of this database, should consider whether these are widely used technologies in your setting.
Validity of estimate of measure of benefit Taken together the two papers describe a well designed study with an adequate, and representative, sample size. However, some caution is warranted due to the higher proportion of patients with a proven bacterial infection in the roxithromycin group.
Validity of estimate of costs The costing methods and sources of price data were reported in adequate detail. The quantities of resource use were not, however, reported separately from costs.
Other issues In general, the conclusion that the cost savings can be achieved seems to be justified. Although the authors reported the total incremental net benefit per clinical success, combining costs and benefits is not appropriate if there is no demonstrated difference in effectiveness or if one of the alternatives is both less costly and more effective.
Source of funding Supported by a grant from ROUSSEL UCLAF.
Bibliographic details Scott W G, Cooper B C, Scott H M. Pharmacoeconomic evaluation of roxithromycin versus amoxycillin clavulanic acid in a community-acquired lower respiratory tract infection study. Infection 1995; 23(Supplement 1): S21-S24 Other publications of related interest Karulus N C et al. Roxithromycin 150 mg b.i.d. versus Amoxycillin 500mg/clavulanic acid 125 mg t.i.d. for the treatment oflower respiratory tract infections in general practice. Infection 1995;23(Supplement 1):S15-S20.
Indexing Status Subject indexing assigned by NLM MeSH Adolescent; Adult; Aged; Amoxicillin /economics /therapeutic use; Amoxicillin-Potassium Clavulanate Combination; Clavulanic Acids /economics /therapeutic use; Cost-Benefit Analysis; Drug Therapy, Combination /therapeutic use; Female; Humans; Male; Middle Aged; Respiratory Tract Infections /drug therapy /economics; Roxithromycin /economics /therapeutic use AccessionNumber 21995000425 Date bibliographic record published 31/12/1998 Date abstract record published 31/12/1998 |
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