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Cost effectiveness of controlled-release oxybutynin compared with immediate-release oxybutynin and tolterodine in the treatment of overactive bladder in the UK, France and Austria |
Guest J F, Abegunde D, Ruiz F J |
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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 use of controlled-release (CR) oxybutynin (at a dose titrated up to 10 mg/day) for the treatment of overactive bladder (OAB). The comparators were immediate-release (IR) oxybutynin (at a dose titrated up to 10 mg/day) and tolterodine (at a dose titrated up to 4 mg/day).
Economic study type Cost-effectiveness analysis.
Study population The study population comprised OAB patients who were over 18 years of age, and who had urge or mixed incontinence with a primary urge component.
Setting The setting was primary care in the UK and secondary care in France and Austria.
Dates to which data relate The effectiveness data were derived from studies published between 1997 and 2001. The resource use data were derived from a panel of clinicians and a specific date was not reported. The price year was 2000/01.
Source of effectiveness data The effectiveness evidence was derived from a systematic review of the literature and authors' assumptions.
Modelling Three decisions models were used to estimate the cost and effectiveness of the treatments evaluated over the course of 6 months. One model depicted the treatment of OAB patients in a primary care setting (the UK), while the other two considered that a specialist would treat OAB patients (France and Austria). Within the models, the patient might continue treatment for 6 months, or experience an adverse event or inefficacy. In the case of an adverse event or inefficacy, patients could subsequently:
switch to another drug;
have the dosage of their initial drug reduced and receive an adjunctive drug;
have their drug treatment combined with behavioural therapy and physiotherapy;
be referred for surgery;
discontinue drug treatment and only receive behavioural therapy and physiotherapy;
discontinue drug treatment and only receive electrotherapy; or
discontinue all treatments.
Outcomes assessed in the review The outcomes derived from the literature were the reduction in the frequency of incontinence and the probability of experiencing an adverse effect reaction. Published data were also used to estimate the percentage reduction in the frequency of micturition for some of the therapeutic options evaluated in the model.
Study designs and other criteria for inclusion in the review A systematic search of the literature was performed to identify relevant primary studies. The search strategy was not limited by year of publication, but only English language papers were included.
Sources searched to identify primary studies MEDLINE, EMBASE, HealthSTAR, Current Contents, NHS EED and Cochrane databases were searched for papers on OAB. A manual literature search was also undertaken, based on citations in the published papers.
Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included At least 19 primary studies were used to estimate clinical outcomes.
Methods of combining primary studies The authors stated that data from different published studies pertaining to comparable populations with OAB were combined to generate pooled clinical outcomes. There were no further details of the method of combination used.
Investigation of differences between primary studies No differences between the primary studies were investigated.
Results of the review The probability of an adverse drug reaction was 0.322 with CR oxybutynin, 0.566 with IR oxybutynin and 0.377 with tolterodine.
Patients treated with IR oxybutynin experienced a 72% reduction in frequency of incontinence and a 20% reduction in frequency of micturition.
Patients treated with CR oxybutynin experienced a 79% reduction in frequency of incontinence and 27% reduction in frequency of micturition.
Patients treated with tolterodine experienced a 58% reduction in frequency of incontinence and 22% reduction in frequency of micturition.
Those patients who underwent surgery experienced a 77% reduction in frequency of incontinence.
Patients treated with electrotherapy experienced a 40% reduction in frequency of incontinence and 21% reduction in frequency of micturition.
Patients treated with behavioural therapy experienced a 69% reduction in frequency of incontinence and 23% reduction in frequency of micturition.
Patients treated with behavioural therapy plus drug treatment had a 16% increase in the reduction in frequency of incontinence compared with any individual drug treatment alone.
Methods used to derive estimates of effectiveness Some model parameters were derived from experts' opinion and authors' assumptions.
Estimates of effectiveness and key assumptions The probabilities of changing treatments were obtained from the clinical interviews. Therefore, these probabilities were country specific.
The frequency of incontinence and the percentage reduction in micturition frequency for those who require adjunctive drug treatment in addition to either oxybutynin (IR or CR) or tolterodine was estimated through expert opinion. It was assumed that patients treated with adjunctive drug treatment with either oxybutynin (IR or CR) or tolterodine had a 50% reduction in frequency of incontinence and micturition compared with drug treatment alone.
It was assumed that surgery and behavioural therapy reduce micturition frequency in the same ratio as the anticholinergic drugs (i.e. 25.1% and 22.5%, respectively).
It was assumed that behavioural therapy combined with drugs reduce micturition frequency in the same ratio as that of incontinence reduction.
The treatment of OAB in this study was modelled up to 6 months by assuming that the clinical outcomes seen in trials after 3 months would be maintained for at least another 3 months.
Measure of benefits used in the economic analysis The summary measures of benefit used in the model were the expected reductions in the numbers of daily incontinence episodes and daily micturition at 6 months following the start of OAB treatment.
Direct costs Discounting was not applied since the time horizon of the model was 6 months. The unit costs were reported separately from the quantities of resource used in each country. The economic evaluation comprised the costs of drug treatment, surgery, outpatient visits, pads, inpatient stay, laboratory tests, and also the cost of transportation for patients. The treatment patterns for each country were estimated by a panel of clinical experts (10 general practitioners in the UK, 9 specialists in France and 16 specialists in Austria). The unit costs were obtained mainly from the literature and included actual costs and official tariffs. CR oxybutynin was not available in Austria and France at the time of performing the study, so its acquisition cost was assumed to be the same as that in the UK where it was available. The price year was 2000/01.
Statistical analysis of costs The costs were treated stochastically in the sensitivity analyses (see 'Sensitivity Analysis' section below for more details).
Indirect Costs The cost of lost productivity related to OAB was also considered in the model. The human capital approach was used to estimate the indirect costs. The costs and the quantities were reported separately. Discounting was not applied since the time horizon of the model was 6 months. The price year was 2000/01.
Sensitivity analysis Probabilistic sensitivity analyses were performed. Monte Carlo simulations (10,000 iterations) were undertaken by simultaneously varying the probabilities, resource use values and clinical outcomes. The probabilities and clinical outcomes were varied randomly according to a beta and log-normal distribution, respectively, between the upper and lower 95% confidence limits. The resource use estimates were varied randomly according to a log-normal distribution by assuming a 50% standard deviation around the mean. One-way sensitivity analyses were also performed.
Estimated benefits used in the economic analysis The daily number of incontinence episodes at 6 months changed as follows:
in the UK, from 3.6 to 1.0 with CR oxybutynin, from 3.6 to 1.4 with IR oxybutynin, from 3.6 to 1.6 with tolterodine;
in France, from 3.6 to 1.0 with CR oxybutynin, from 3.6 to 1.6 with IR oxybutynin, and from 3.6 to 1.9 with tolterodine; and
in Austria, from 3.6 to 0.9 with CR oxybutynin, from 3.6 to 1.4 with IR oxybutynin, and from 3.6 to 1.3 with tolterodine.
The daily number of micturitions at 6 months changed as follows:
in the UK, from 11.5 to 8.7 with CR oxybutynin, from 11.5 to 9.5 with IR oxybutynin, and from 11.5 to 9.2 with tolterodine;
in France, from 11.5 to 8.7 with CR oxybutynin, from 11.5 to 9.7 with IR oxybutynin, and from 11.5 to 9.5 with tolterodine; and
in Austria, from 11.5 to 8.6 with CR oxybutynin, from 11.5 to 9.3 with IR oxybutynin, and from 11.5 to 9.1 with tolterodine.
Cost results The expected health care costs per OAB patient at 6 months were:
in the UK, EUR 1,078.05 for CR oxybutynin, EUR 1,097.30 for IR oxybutynin, and EUR 1,359.20 for tolterodine;
in France, EUR 872.91 for CR oxybutynin, EUR 834.25 for IR oxybutynin, and EUR 861.90 for tolterodine; and
in Austria were EUR 912.84 for CR oxybutynin, EUR 986.64 for IR oxybutynin, and EUR 1,108.71 for tolterodine.
The expected direct costs to a patient 6 months after starting OAB treatment were:
in the UK, EUR 229.74 with CR oxybutynin, EUR 226.69 with IR oxybutynin, and EUR 228.02 with tolterodine;
in France, EUR 735.25 with CR oxybutynin, EUR 716.83 with IR oxybutynin, and EUR 920.23 with tolterodine, and
in Austria, EUR 979.96 with CR oxybutynin, EUR 972.82 with IR oxybutynin, and EUR 1,002.23 with tolterodine.
Irrespective of the initial treatment, the indirect costs (lost productivity costs) were EUR 84 in the UK, EUR 250 in France, and EUR 98 in Austria.
Synthesis of costs and benefits The incremental cost-effectiveness of CR oxybutynin relative to the other treatments was calculated.
In the UK and Austria, starting OAB treatment with CR oxybutynin proved to be a dominant strategy relative to either IR oxybutynin or tolterodine, as it improved clinical outcomes (reduction in the frequency of incontinence and micturition frequency) at a lower cost.
In France, the cost for an additional reduction in the number of daily incontinence episodes was EUR 64 for CR oxybutynin relative to IR oxybutynin and EUR 12 for CR oxybutynin relative to tolterodine. The cost for an additional reduction in the number of daily micturitions was EUR 39 for CR oxybutynin relative to IR oxybutynin and EUR 14 for CR oxybutynin relative to tolterodine.
The Monte Carlo simulation showed that when CR oxybutynin was found to be dominant, this result would be expected in at least half of the cohort. In contrast, when a treatment strategy was found to have additional costs (as CR oxybutynin did in France), the relative cost-effectiveness of these strategies would be dominant in at least 40% of the cohort.
The one-way sensitivity analyses showed that from the payer's perspective, the model results in France were sensitive to the number of specialist visits. The results of the UK and Austrian models were not sensitive to changes in any of the resources use values. From the patient's perspective, the key variables were shown to be the number of incontinence pads used per day and the transportation costs.
Authors' conclusions Starting treatment of overactive bladder (OAB) with controlled-release (CR) oxybutynin is expected to be a more effective strategy than starting with either immediate-release (IR) oxybutynin or tolterodine over 6 months of treatment. CR oxybutynin is potentially the most cost-effective strategy in the UK, France and Austria.
CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparators was clear since the most common treatments for OAB patients were considered in the analysis. You should decide if they are valid comparators in your own settings.
Validity of estimate of measure of effectiveness The clinical evidence came mainly from a systematic review of the literature. This approach should ensure the validity of the primary data. However, the methods used to extract and combine the primary data were not described in detail, and it was assumed that the results obtained in the clinical trials at 3 months would be maintained up to 6 months. Moreover, some data were derived from expert opinion. Nevertheless, the impact of these limitations on the study conclusions is likely to be low since comprehensive sensitivity analyses were performed.
Validity of estimate of measure of benefit The measures of benefit used in the models were based on the effectiveness analysis. Therefore, the commentaries reported earlier are also applicable here. It would have been useful had the quality of life associated with each treatment been taken into consideration, since this might represent an important issue for a patient with OAB.
Validity of estimate of costs The authors explicitly reported the perspectives adopted in the study. However, since the indirect costs were included in the cost analysis, it appears that a further perspective (i.e. societal) has been considered. The costs and the quantities of resource used in each country were reported separately. This will enhance the reproducibility of the study in other settings. It seems that all the costs relevant to the perspectives adopted were considered in the study. The sources of the cost data and the price year were reported, thus enhancing any future reflation exercises. The costs were treated deterministically, but comprehensive sensitivity analyses were performed to assess the robustness of the cost estimates used. Discounting was not conducted, but would not have been relevant given the short time horizon.
Other issues The authors compared their results with those of other studies. The differences between the results obtained in the UK, France and Austria were discussed. The issue of generalisability of the study results to other settings was not explicitly addressed. However, the price year and the unit costs were reported and comprehensive sensitivity analyses were performed. These enhance the possibility of replicating the analysis in other settings. The authors reported a number of limitations to their study. First, the analysis did not account for the non-clinical dimensions of OAB. Second, the analysis did not incorporate changes in quality of life experienced by patients with OAB. Finally, the willingness to pay for improvements in reducing daily number of micturitions and leakages was not considered.
Implications of the study The authors did not make any explicit recommendations for changes in policy and practice, or the need for further research. However, the study results support the use of CR oxybutynin for OAB patients in the UK, France and Austria.
Source of funding Supported by Sanofi-Synthelabo.
Bibliographic details Guest J F, Abegunde D, Ruiz F J. Cost effectiveness of controlled-release oxybutynin compared with immediate-release oxybutynin and tolterodine in the treatment of overactive bladder in the UK, France and Austria. Clinical Drug Investigation 2004; 24(6): 305-321 Indexing Status Subject indexing assigned by NLM AccessionNumber 22004000923 Date bibliographic record published 30/06/2006 Date abstract record published 30/06/2006 |
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