|
Acute uncomplicated UTI and E. coli resistance: implications for first-line empirical antibiotic therapy |
Perfetto E M, Keating K, Merchant S, Nichols B R |
|
|
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 compared two first-line antibiotic therapies for the treatment of acute uncomplicated urinary tract infection (UTI), which in approximately 80% of cases is caused by Escherichia coli (E. coli) . The two treatments were administered for a 3-day period. The treatments were trimethoprim-sulfamethoxazole (TMP-SMX; 800-160 mg twice daily) and ciprofloxacin XR (Cipro XR; 500 mg once daily).
Economic study type Cost-effectiveness analysis.
Study population The main characteristics of the patient or target population studied were not described.
Setting The setting was primary care. The economic study was carried out in the USA.
Dates to which data relate The effectiveness data were derived from literature published between 1999 and 2003. The dates relating to the cost data were not reported, nor was the price year.
Source of effectiveness data The data were derived from a review or synthesis of completed studies, augmented by authors' assumptions.
Modelling The authors constructed a cost-minimisation model, using a Microsoft Excel spreadsheet, to test five clinical scenarios comparing empiric TMP-SMX with empiric Cipro XR for the treatment of uncomplicated UTI. The scenarios tested were as follows.
Scenario 1a: a base-case scenario using national average resistance rates for uncomplicated UTI for both treatments, based on 2001 data from 38 US states reported in the Surveillance Network, Focus Technologies.
Scenario 1b: a base-case scenario using national average resistance rates for UTI based on regional data published in another study.
Scenario 2: a financial break-even analysis in which the threshold local TMP-SMX-E.coli resistance was explored by keeping the resistance rate for Cipro XR constant at 1.0%.
Scenario 3: a telephone treatment protocol scenario in which an initial office visit and an initial urinalysis were averted since prescribing was carried out by telephone.
Scenario 4: a treatment scenario using data reported on the average duration of therapy for each antibiotic used to treat uncomplicated UTI.
Scenario 5: a worst-case scenario for ciprofloxacin resistance (10%).
The model was based on the following assumptions. The initial office visit included only an in-office urinalysis, but no culture or sensitivity testing. Both treatment options were delivered for 3 days, and after this period infections were either cured or persistent. Persistent infections were assumed to necessitate a second visit, either to the physician or to an emergency room (ER). The second visit was assumed to include a second urinalysis, an initial urine culture and laboratory sensitivity test, and a successful 7-day treatment with a different antibiotic. The time horizon was unclear.
Outcomes assessed in the review Although the input parameters of the model were not reported explicitly, it appears that the following parameters were used:
the rate of local antibiotic resistance,
the rates of clinical failure and success after initial treatment,
the percentage of failures that result in an ER visit for treatment,
the percentage of failures that result in a second physician's office visit,
the rates of success after the ER visit and second office visit.
Study designs and other criteria for inclusion in the review The authors did not report the study designs eligible for inclusion in the review. They do not seem to have used strict inclusion criteria pertaining to study design.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data The authors did not state any methods used to judge the relevance and validity of the data.
Number of primary studies included Although not explicitly reported, it seems that five primary studies were included as sources of effectiveness evidence.
Methods of combining primary studies The authors do not appear to have combined the results of the individual studies.
Investigation of differences between primary studies No differences between the primary studies were investigated.
Results of the review The success rate after an initial office visit was 92.35% with TMP-SMX and 99.5% with Cipro XR.
The failure rate among TMP-SMX-resistant patients treated with TMP-SMX was 50%.
Among those who failed first-line therapy, the success rate after a second office visit was 7.04% with TMP-SMX and 0.45% with Cipro XR.
Among those who failed first-line therapy, the success rate after an ER visit was 0.61% with TMP-SMX and 0.04% with Cipro XR.
In the 1a scenario, the average TMP-SMX and ciprofloxacin E. coli resistance rates for uncomplicated UTI isolates were 15.31% and 1.03%, respectively.
In the 1b scenario, the average TMP-SMX and ciprofloxacin E. coli resistance rates for UTI were 16.1% and 2.5%, respectively.
Methods used to derive estimates of effectiveness The authors made assumptions, based on the available medical literature, about some measures of effectiveness.
Estimates of effectiveness and key assumptions The failure rate of Cipro XR was assumed to equal that of TMP-SMX administered to TMP-SMX-resistant patients (50%).
All TMP-SMX-susceptible infections and ciprofloxacin-susceptible infections were assumed to be cured when treated with TMP-SMX and ciprofloxacin, respectively.
At the initial stage of therapy, patients were assumed not to visit ERs.
The percentage of failures that resulted in an ER visit was 8%, while the percentage of failures that resulted in a second physician's office visit was 92%.
Measure of benefits used in the economic analysis The authors did not derive a summary measure of benefit in the economic analysis. The study was therefore characterised as a cost-consequences analysis.
Direct costs From the perspective of the MCO, the direct medical costs included in the analysis were for the drugs (generic TMP-SMX and Cipro XR at the described doses), the physician's fee for an office visit, the physician's fee for processing a urinalysis; laboratory fees for a urinalysis, laboratory fees for culture and sensitivity test, emergency department visit, emergency department laboratory fees for culture and sensitivity test, and second antibiotic treatment administered for 7 days after failure of initial treatment.
The unit costs were explicitly described. All the costs were derived from reimbursement amounts provided by a major employee health and benefit plan provider, based in the mid-Atlantic region of the USA. The model also incorporated co-payments for office visits, for a generic TMP-SMX prescription, and for a brand-name prescription. The second drug was assumed to be a branded product at equal per-dose cost to Cipro XR and prescribed once daily for 7 days. All the quantities of resources used were derived from the model. The price year was not reported. Discounting was not relevant as the costs were incurred during a short time (less than 2 years).
Statistical analysis of costs The costs were treated deterministically. Therefore, no statistical analysis of the costs was undertaken.
Indirect Costs The indirect costs were not included in the analysis.
Sensitivity analysis No sensitivity analysis was carried out.
Estimated benefits used in the economic analysis See the 'Effectiveness Results' section.
Cost results The total costs were reported per patient.
In scenario 1a, the average total treatment cost was $59.40 with TMP-SMX (resistance rate 15.3%) and $49.19 with Cipro XR (resistance rate 1.0%).
In scenario 1b, the average total treatment cost was $60.14 with TMP-SMX (resistance rate 15.3%) and $50.55 with Cipro XR (resistance rate 1.0%).
In the break-even analysis (scenario 2), an average total treatment cost of $49.19 was achieved when the threshold resistance rate of TMP-SMX was 4.3% and the ciprofloxacin resistance rate was 1.0%.
In scenario 3 (excluding office visits and cost of urinalysis), the average cost per patient (with a resistance threshold of 4.3%) was $4.19 for both treatment options.
In scenario 4, the threshold rate of TMP-SMX resistance was 2.8% for an equal treatment cost of $54.87.
In the worst-case scenario (with a Cipro XR resistance rate of 10%), the TMP-SMX resistance threshold rate increased to 13.3% to reach an average treatment cost of $57.50 for both groups.
Synthesis of costs and benefits The costs and benefits were not combined.
Authors' conclusions When using costs typical of a managed care organisation (MCO) and national estimates of resistance (i.e. local TMP-SMX-E. coli resistance exceeds 10% and ciprofloxacin resistance varies between 0.5 and 6%), the total average cost for ciprofloxacin XR (Cipro XR)-treated patients is less than that of trimethoprim-sulfamethoxazole (TMP-SMX)-treated patients. Thus, Cipro XR is a more cost-effective option than standard empiric treatment in areas where local Escherichia coli (E. coli) resistance to TMP-SMX exceeds guideline-recommended levels.
CRD COMMENTARY - Selection of comparators A justification was provided for the comparators chosen. However, the authors acknowledged that other common first-line therapies (e.g. nitrofurantoin) or second-line agents (e.g. cephalexin) were not considered. You should decide if the comparator chosen is relevant in your setting, or whether other comparators of other drugs could also be relevant.
Validity of estimate of measure of effectiveness The authors did not state that a systematic review of the literature had been carried out. The authors used data from the available studies selectively. Although this is common practice with models, since no details of the search strategy were reported, uncertainty about the literature search and possible omission of relevant studies remains. The authors did not note any differences between the efficacy estimates from the primary studies. There was also little commentary on the quality of the retrieved studies, making it difficult to comment on the quality of the efficacy estimates. In addition, the characteristics of the target population were not described, thus limiting the generalisability of the findings. There was insufficient justification for the authors' clinical assumptions, and the methods used to derive them were not reported. The estimates used were also not investigated in a sensitivity analysis, to assess the robustness of the results to changes in the base-case estimates.
Validity of estimate of measure of benefit The authors did not derive a summary measure of benefit. Although it was reported that a cost-minimisation analysis was undertaken, equal effectiveness of the two treatment options was not demonstrated in the analysis. The study was therefore characterised as a cost-consequences analysis.
Validity of estimate of costs The economic analysis adopted the perspective of an MCO or health insurer. As such, it seems that all the relevant categories of costs have been included in the analysis. The authors reported that generic ciprofloxacin (250 mg given twice per day) was not considered because the payer's cost per treated patient was considerably higher than both the brand-name Cipro XR and generic TMP-SMX. In addition, they reported that the model did not consider yeast infections and hospitalisation for pyelonephritis, although the omission of the latter costs might not have affected the authors' conclusions.
The unit costs were reported, but no statistical or sensitivity analyses on the costs were performed to assess the robustness of the estimates used. Although not explicitly reported, it is possible that charges were used to proxy costs since the cost data were derived from a major employee health and benefit plan provider, which further limits the reproducibility of the results to other settings. Discounting was not necessary as the costs were incurred during less than 2 years. The price year was not reported; this does not enable the analysis to be easily reworked in other settings.
Other issues The authors compared their results with those from published studies, finding consistency in the findings. They reported that differences in findings were mostly due to differences in the sources of the cost data. The issue of generalisability of the results to other settings was addressed. The authors do not appear to have presented their results selectively.
The authors reported a number of limitations to their study. First, the clinical assumptions and cost data were derived from various sources and might not reflect the actual situation for any specific MCO. Second, resistance data from publicly available databases were derived from hospitalised patients and not from primary care patients. Third, evidence in the literature suggested that microbiological resistance may not translate to adverse clinical outcomes. Finally, the authors acknowledged that their model did not account for differences between the therapies, such as increased effectiveness due to better compliance or therapeutic effectiveness.
Karen Keating and Sanjay Merchant are employed by Bayer, and Eleanor Perfetto and Brian Nichols are employed by The Weinberg Group, consultants to Bayer.
Implications of the study The authors suggested that the decision to use an alternative first-line therapy for uncomplicated UTI should not be made on the basis of drug acquisition costs alone. Health care professionals and decision-makers should always take local resistance and susceptibility data into consideration before adopting a new treatment alternative. This means that health care providers, especially primary care physicians, nurse practitioners, physician assistants and pharmacists, must be educated and knowledgeable about pathogen resistance and susceptibility in their geographic area of practice. The authors also suggested that MCOs may need to conduct more internal surveillance to better understand resistance and its implications in their own eligible populations. In the absence of specific internal data on resistance, inpatient E. coli susceptibility data for uncomplicated UTI is a reasonable basis for decision-making. The authors recommended further research on the identification of outpatient resistance rates to help decision-makers make more informed decisions. Their discussion also highlighted areas where further information is needed.
Source of funding Funded by Bayer Pharmaceuticals Inc.
Bibliographic details Perfetto E M, Keating K, Merchant S, Nichols B R. Acute uncomplicated UTI and E. coli resistance: implications for first-line empirical antibiotic therapy. Journal of Managed Care Pharmacy 2004; 10(1): 17-25 Other publications of related interest Le TP, Miller LG. Empirical therapy for uncomplicated urinary tract infections in an era if increasing antimicrobial resistance: A decision and cost analysis. Clin Infect Dis 2001;33:615-21.
Perfetto EM, Gondek K. Escherichia coli resistance in uncomplicated urinary tract infection: a model for determining when to change first-line empirical antibiotic choice. Manag Care Interface 2002;15:35-42.
Li-McLeod J, Cislo P, Gomolin IH. Cost analysis of ciprofloxacin oral suspension vs. trimethoprim/sulfamethoxazole oral suspension for treatment of acute urinary tract infections in elderly women (poster). Conference of American Society of Consultant Pharmacists; 2000 Nov 1-4; Boston, USA.
Indexing Status Subject indexing assigned by NLM MeSH Acute Disease; Adolescent; Adult; Anti-Bacterial Agents /therapeutic use; Anti-Infective Agents /pharmacology /therapeutic use; Ciprofloxacin /pharmacology /therapeutic use; Cost-Benefit Analysis; Cross-Sectional Studies; Drug Resistance, Microbial; Empirical Research; Escherichia coli /drug effects; Escherichia coli Infections /drug therapy; Female; Humans; Middle Aged; United States; Urinary Tract Infections /drug therapy /microbiology AccessionNumber 22004006247 Date bibliographic record published 28/02/2006 Date abstract record published 28/02/2006 |
|
|
|