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Oxybutynin extended release and tolterodine immediate release: a health economic comparison |
Getsios D, Caro J J, Ishak K J, El-Hadi W, Payne K, O'Connel M, Albrecht D, Feng W, Dubois D |
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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 oxybutynin extended release (XL) and tolterodine immediate release (IR) for the treatment of overactive bladder. The doses used were 10 mg/day (oxybutynin) and 4 mg/day (tolterodine), respectively.
Study population The study population comprised a hypothetical UK population of community-dwelling adults with urge or mixed urinary incontinence.
Setting The setting was not explicitly reported, but it was likely to have been primary care and/or secondary care. The economic study was carried out in the UK.
Dates to which data relate The effectiveness data were derived from a study published in 2001. The resource use and cost data were taken from a number of studies published between 1997 and 2002. The health utilities were taken from a study published in 1998. The price year was reported to have been 2002.
Source of effectiveness data The effectiveness data were derived from a non-systematic review of the literature, augmented by the authors' assumptions.
Modelling A state-transition Markov analytic model was used to estimate the benefits and costs. The model was developed to allow the extrapolation of trial data over a longer timeframe. The time horizon of the model was one year. The total number of urinary incontinent episodes (TUI) per week defined the various health states. The model consisted of 5 states, corresponding to a TUI of 0 (total continence), 1 to 6 (minimal incontinence), 7 to 21, 22 to 42, and greater than 42. The cycle length was not reported, although it was likely to have been weekly.
Outcomes assessed in the review The parameters derived from the literature to inform the model were:
the number of TUI events per week,
the proportion of patients achieving complete continence,
the proportion of patients achieving minimal incontinence,
the number of days with no incontinent episodes, and
treatment persistence rates.
Study designs and other criteria for inclusion in the review The review of the literature was non-systematic and no inclusion criteria were specified. However, the majority of the effectiveness data were derived from a single study.
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 Number of primary studies included Approximately two primary studies were used to derive parameters.
Methods of combining primary studies Investigation of differences between primary studies Results of the review The model inputs were not reported within the paper. However, the authors reported some data from the single 3-month study, which was then augmented with authors' assumptions to derive the model inputs.
Methods used to derive estimates of effectiveness The authors made assumptions when deriving the estimates of effectiveness.
Estimates of effectiveness and key assumptions The major assumptions were as follows.
From months 3 to 12 no further changes in disease severity would take place for patients who were compliant with treatment.
A common dropout rate for all patients, irrespective of treatment or disease severity, was applied on the basis of the average drop- out rate over weeks 8 to 12 in the main study (2.1%).
The patients were either fully compliant or discontinued treatment completely, and patients discontinuing treatment returned to their severity at baseline.
The frequency of doctor visits was equal in the two treatment arms, with the only differences arising from treatment discontinuation.
Measure of benefits used in the economic analysis The measures of benefit used were the quality-adjusted life-years (QALYs), incontinent episode avoided, and additional patients achieving complete continence or minimal incontinence.
Utilities were derived from prior research that used the EuroQol to calculate health utilities for various severity states, with severity defined by the daily frequency of voids and accidents (Kobelt et al., see Other Publications of Related Interest). The health utilities for use in the model were obtained using data derived from the OBJECT study and the published utility weights.
Discounting was not relevant and, appropriately, was not conducted.
Direct costs The cost/resource boundary was that of the UK National Health Service. The direct costs included were for the daily drugs, doctor visits, pads or other protection used, and laundry. Resource use was derived from published sources and was augmented with authors' opinions. The unit costs and the resources were not reported separately. The costs were not discounted since the time horizon of the model did not extend beyond 1 year. All the costs were reported in 2002 prices.
Statistical analysis of costs The costs were treated deterministically.
Indirect Costs The indirect costs were not included.
Currency UK pounds sterling (). Conversions were made from Australian dollars (Aus$) and US dollars ($), but the conversion rates were not reported.
Sensitivity analysis Sensitivity analyses were conducted on the assumptions made in projecting outcomes and key model inputs. The model inputs investigated were all non-drug costs (25 - 400% of the base-case estimates), the cost of oxybutynin XL (50 - 200% of the actual price of oxybutynin XL), and treatment discontinuation rates (up to 400% higher than base-case estimates). Although not explicitly stated, it would appear that both univariate and multivariate sensitivity analyses were conducted.
The impact of including costs such as those related to co-morbidities was also analysed, using a broad "all other costs" category, which was not included in the main analysis. In this sensitivity analysis it was assumed that all patients attaining complete continence avoided these costs, whereas patients with minimal incontinence avoided only half of these costs. All other patients incurred these costs fully.
Estimated benefits used in the economic analysis The gain in QALYs was 0.004 for oxybutynin XL (0.690 QALYs) compared with tolterodine IR (0.686 QALYs).
After 1 year, 3.1 more patients per 100 treated attained complete continence with oxybutynin XL compared with tolterodine IR. In addition, 5.6% more had less than 7 incontinent episodes per week.
Over 1 year, patients receiving oxybutynin XL had almost 17 additional incontinence-free days and 95 fewer incontinent episodes.
Cost results The cost of the drug per patient was 326 with tolterodine IR and 251 with oxybutynin XL. The net result was -75. Other direct costs per patient were 92 with tolterodine IR and 81 with oxybutynin XL. The net result was -11.
Hence, the total cost per patient over the course of 52 weeks was 418 with tolterodine IR and 332 per patient with oxybutynin XL. Th net result was -86.
Synthesis of costs and benefits The costs and benefits were not combined since oxybutynin XL was found to be the dominant strategy (i.e. less costly and more effective).
Overall, the sensitivity analyses showed the results to be fairly robust. Using alternative assumptions for projections of effectiveness and treatment persistence, varying health utilities and non-pharmaceutical costs all failed to alter the result that oxybutynin XL was the dominant strategy. Both pharmaceutical costs and discontinuation rates had more of an impact on the results. However, the drug costs would have to increase by about 34% to have any impact, and the discontinuation rates would have to triple before a change in strategy would even be considered. Full details were reported in the paper.
Authors' conclusions Given the current prices and available data, oxybutynin extended release (XL) should clearly be the preferred treatment to tolterodine immediate release (IR).
CRD COMMENTARY - Selection of comparators A justification was given for the comparator. It represented a viable treatment option for overactive bladder and, more importantly, head-to-head data were available for the analyses. A comparison with the XL formulation of tolterodine (or other available options) may have been preferable. However, a lack of data meant that this was not a viable choice for this analysis. You should decide if tolterodine IR represents a valid comparator in your own setting.
Validity of estimate of measure of effectiveness The authors did not undertake a systematic review of the literature. The majority of the effectiveness data were derived from a single study. The study was a blinded, randomised controlled trial. The details of the study were not reported and, as such, it is difficult to assess the internal validity. Many of the estimates were augmented with authors' assumptions, the majority of which were justified using published literature. Sensitivity analyses were conducted to assess the robustness of the assumptions, the projected efficacy, and the tolerability outcomes. The overall validity of the model inputs is difficult to assess given the level of reporting, which in turn reflects on the validity of the model outcomes.
Validity of estimate of measure of benefit The authors used both disease-specific benefit measures (incontinence episode avoided and additional patient achieving complete continence or minimal incontinence) and QALYs. The utilities were derived from the literature and were adjusted appropriately for incorporation into the model. Sensitivity analyses around the utilities were conducted, although no justification for the ranges used was given.
Validity of estimate of costs The costs were analysed from the perspective of the National Health Service paying for the treatment. Only the direct costs of treatment were included, and the costs associated with admissions to care homes and co-morbid conditions were excluded. These additional costs were included in a secondary analysis. Some of the non-drug costs and co-morbid costs were derived from studies conducted in other countries and, although currency conversions were conducted, the conversion rates were not reported. Discounting was not relevant given the one-year timeframe and, appropriately, was not conducted. Although the costs were reported, resource use was not. The price year was given, which will aid reflation exercises in the future. Overall, the external validity of the cost results is difficult to assess given the level of reporting.
Other issues The authors made comparisons with the one other study, conducted in the USA, which compared the two relevant treatments. Although that studied used pooled results, the overall findings suggested the same dominance. The authors did not explicitly address the issue of generalisability of the results to other settings. The authors did not appear to have presented their results selectively, but the reporting could have been clearer. The conclusions reached reflected the scope of the analysis and the authors clearly outlined the limitations to their study.
Implications of the study Oxybutynin XL is less expensive than tolterodine IR and would result in lower costs to the health care system, even if both drugs were equally effective. According to the authors, given the current prices and available data, oxybutynin XL should clearly be the preferred treatment option compared with tolterodine IR. However, it is worth bearing in mind that other treatments are available for overactive bladder and should be considered as comparators in any further analysis.
Source of funding Supported in part by a grant from Janssen Pharmaceutica.
Bibliographic details Getsios D, Caro J J, Ishak K J, El-Hadi W, Payne K, O'Connel M, Albrecht D, Feng W, Dubois D. Oxybutynin extended release and tolterodine immediate release: a health economic comparison. Clinical Drug Investigation 2004; 24(2): 81-88 Other publications of related interest Appell RA, Sand P, Dmochowski R, et al. Prospective randomized controlled trial for extended release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder: results of the OBJECT study. Mayo Clinic Proceedings 2001;76:358-63.
Diokno A, Sand P, Labasky R, et al. Long-term safety of extended-release oxybutynin chloride in a community-dwelling population of participants with overactive bladder: one-year study. International Urology and Nephrology 2002;34:43-9.
Kobelt G, Jonsson L, Mattiason A. Cost-effectiveness of new treatments for overactive bladder: the example of tolterodine, a new muscarinic agents: a Markov model. Neurourology and Urodynamics 1998;17:599-611.
Arikian SR, Casciano J, Doyle JJ, et al. A pharmacoeconomic evaluation of two new products for the treatment of overactive bladder. Managed Care Interface 2000;13:88-94.
Sussman D, Garely A. Treatment of overactive bladder with once-daily extended-release tolterodine or oxybutynin: the Antimuscarinic Clincal Effectiveness Trial (ACET). Current Medical Research and Opinion 2002;18:177-84.
Indexing Status Subject indexing assigned by NLM AccessionNumber 22004000442 Date bibliographic record published 31/01/2005 Date abstract record published 31/01/2005 |
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