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Single-dose oral ciprofloxacin versus placebo for prophylaxis during transrectal prostate biopsy |
Kapoor D A, Klimberg I W, Malek G H, Wegenke J D, Cox C E, Patterson A L, Graham E, Echols R M, Whalen E, Kowalsky S F |
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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 prophylaxis (a single oral 500-mg dose of ciprofloxacin administered before the diagnostic procedure) in the prevention of infections in patients undergoing transrectal needle biopsy of the prostate.
Economic study type Cost-effectiveness analysis.
Study population Male patients at least 18 years of age who required transrectal needle biopsy of the prostate. The exclusion criteria were as follows: history of hypersensitivity to ciprofloxacin or other quinolones, valvular heart disease requiring prophylaxis for bacterial endocarditis, significant gastrointestinal disease or inability to tolerate oral medication, history of suspected or established epilepsy, presence of bacteriuria (more than 10^4 colony-forming units (CFU/mL) from preprocedure urine culture, history of endoscopic manipulation of the urinary tract within 7 days of study enrolment, presence of indwelling bladder catheter for more than 24 hours before needle biopsy, absolute granulocyte count less than 1000/mm^3, and antibiotic(s) given within 1 week of the needle biopsy.
Setting Hospital. The economic study was carried out in the USA.
Dates to which data relate Effectiveness and resource use data corresponded to patients examined between January 1992 and March 1993. The price year appears to have been 1993.
Source of effectiveness data The evidence for the final clinical outcomes was derived from a single study.
Link between effectiveness and cost data Costing was retrospectively undertaken on the same patient sample as that used in the effectiveness analysis.
Study sample Power calculations were not used to determine the sample size. The study sample consisted of 537 patients with a mean age of 69.1 (range: 41 - 88) years, who were randomly assigned to either the intervention (ciprofloxacin) group (n=269) or to the placebo group (n=268). The original number of randomised patients was 557, of whom 20 (10 in each group) from one study site were excluded from the analysis because clinical and laboratory data could not be verified.
Study design This was a multicentre, randomised, double blind, placebo-controlled trial, carried out in 5 sites (originally 6 sites, one site later being excluded because clinical and laboratory data could not be verified.). Randomisation was carried out using a computer-generated schedule. The duration of the follow-up was 15 days after the biopsy. The loss to follow-up (including absence of required cultures or violation of entry criteria) was 52 (18.6%) in the intervention group and 48 (17.3%) in the placebo group, (p=0.6732).
Analysis of effectiveness The principle used in the analysis of effectiveness was both intention to treat and treatment completers only (efficacy population). The primary efficacy outcome was the rate of bacteriuria (more than 10^4 CFU/mL). Clinical response was a secondary determinant of efficacy and was the proportion of patients with an end of study response of success (no clinical symptoms of a urinary tract infection (UTI)) versus failure (clinical signs of UTI). Repeated urine cultures and urinalysis were obtained at 2 to 6 days and 9 to 15 days after the biopsy; adverse events being recorded at the same intervals. A Mantel-Haenszel procedure was used to compare difference in efficacy adjusting for centre. Consistency of results across centres was tested using a Breslow-Day test. The effects of some confounding variables such as number of biopsies, time between dosing and biopsy, and use of enema before procedure on primary efficacy variable were assessed. Patients not reporting adverse events compared with those experiencing adverse events stratified clinical outcome data. The patient groups (efficacy population) were comparable in terms of demographic and baseline medical features.
Effectiveness results The percentage of patients having bacteriuria (more than 10^4 CFU/mL) was 3% in the intervention group and 8% in the placebo group (p=0.009).
Clinical signs of UTI were observed in 3% of patients in the intervention group and 5% of patients in the placebo group (p=0.15).
Only the adverse event category labelled "body-as-a-whole" (e.g., fever, chills, pain) was statistically significant and was reported in 2% of patients in the intervention group versus 6% in the placebo group, (p=0.019).
Hospitalisation due to febrile UTI occurred in 2% of patients in the placebo group versus 0% in the intervention group.
Clinical conclusions The study described here demonstrates that there is substantial clinical benefit from using antimicrobial prophylaxis in the performance of transrectal needle biopsy of the prostate, and that a single 500-mg dose of ciprofloxacin is adequate for this purpose.
Modelling A decision tree was constructed to represent resource use under routine medical care using clinical probabilities from the trial.
Measure of benefits used in the economic analysis No summary benefit measure was identified in the economic analysis, and only clinical outcomes were reported separately.
Direct costs Costs were not discounted due to the short time frame of the cost analysis. Quantities were not reported separately from the costs. Cost items were not reported separately. Cost analysis covered the direct costs of treating postsurgical complications of infection and ciprofloxacin. The perspective adopted in the cost analysis was not explicitly specified. The resource use was modelled using a decision tree based on four economic outcomes: successful prophylaxis, asymptomatic failure, symptomatic failure treated without hospitalisation, and symptomatic failure requiring hospitalisation. The source of cost data for infection treatment was health maintenance organisation utilisation data. The Redbook was the source of average wholesale price of ciprofloxacin. The price year appears to have been 1993. The costs of adverse events were not included in the cost analysis.
Estimated benefits used in the economic analysis Cost results The expected treatment cost of infectious complications was reduced by $23 per patient as a result of using ciprofloxacin. It was projected that the intervention would be associated with annual savings of $68,195 in the five study centres.
Synthesis of costs and benefits Costs and benefits were not combined since the intervention appears to have been the dominant strategy.
Authors' conclusions Single-dose oral ciprofloxacin reduced bacteriuria after biopsy compared with placebo in patients undergoing transrectal prostatic biopsy and provided an economic advantage. In addition, this study establishes the actual rate of bacteriuria after transrectal needle biopsy of the prostate without antibiotic prophylaxis to be 8% with a clinical rate of 5% and a hospitalisation rate of 2%.
CRD COMMENTARY - Selection of comparators The authors chose placebo as a comparator for the intervention drug, which allowed the active value of the treatment to be evaluated. Other, more appropriate comparators could have been considered, such as the usual practice in the authors setting.
Validity of estimate of measure of effectiveness The effectiveness results are likely to be internally valid given the randomised design of the study, intention to treat analysis, and adjustments made for confounding variables. However, in the intention to treat analysis, ten patients in each group were excluded from one site, as data could not be verified. Furthermore, comparability of groups in terms of demographic and prognostic features was reported for the treatment completers analysis only. The patient sample appears to have been representative of the study population.
Validity of estimate of measure of benefit The authors did not derive a measure of health benefit. The study may therefore be regarded as a cost-consequences analysis.
Validity of estimate of costs Quantities were not reported separately from the costs and insufficient details of methods of cost estimation were given. It is not clear whether not including the costs of adverse events could adversely effect the internal validity of the cost analysis (due to ambiguous results regarding the group difference). The effects of different procedures on indirect costs (productivity loss) were not evaluated. Based on the information provided, it is not clear whether the cost analysis was based on charge data or true costs. The cost results may not be generalisable to other settings or countries.
Other issues The issue of generalisability to other settings or countries was not addressed, although appropriate comparisons were made with other studies. How representative the study sample was to the study population was not explicitly discussed.
Implications of the study The authors believe that this study demonstrates that routine antimicrobial prophylaxis should be mandatory before transrectal needle biopsy of the prostate and that a single preprocedure dose of oral ciprofloxacin is an adequate regimen to prevent infectious complications from this procedure.
Source of funding Research grant from Bayer Corporation, Pharmaceutical Division, West Haven, Connecticut, USA.
Bibliographic details Kapoor D A, Klimberg I W, Malek G H, Wegenke J D, Cox C E, Patterson A L, Graham E, Echols R M, Whalen E, Kowalsky S F. Single-dose oral ciprofloxacin versus placebo for prophylaxis during transrectal prostate biopsy. Urology 1998; 52(4): 552-558 Indexing Status Subject indexing assigned by NLM MeSH Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Infective Agents /administration & Antibiotic Prophylaxis; Biopsy, Needle /methods; Ciprofloxacin /administration & Double-Blind Method; Humans; Male; Middle Aged; Prospective Studies; Prostate /pathology; Rectum; dosage; dosage AccessionNumber 21998001491 Date bibliographic record published 30/11/2000 Date abstract record published 30/11/2000 |
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