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The cost utility of bisphosphonate treatment in established osteoporosis |
Iglesias C P, Torgerson D J, Bearne A, Bose U |
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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 risendronate, a new bisphosphonate treatment, for the prevention of vertebral and non-vertebral fractures among women with severe osteoporosis.
Study population The study population comprised women with severe osteoporosis, which was defined as pre-existing fragility fracture and low bone mineral density. A hypothetical cohort of 1,000 patients aged 75 years or older was utilised in the modelling aspects of the study. The patients had been receiving risendronate therapy for 3 years, although they stayed in the model until death.
Setting The setting was primary care. The economic study was carried out in the UK.
Dates to which data relate The effectiveness evidence was derived from studies published between 1994 and 2001. The price year was 1999. No dates for resource use were reported.
Source of effectiveness data The effectiveness data were derived from a review of several published studies.
Modelling A Markov simulation model that had been published in the UK was used to estimate the lifetime costs and benefit of the therapy. The cohort used was allowed to move across four health states. These were healthy post-hip fracture, healthy post-vertebral fracture, health post second hip fracture, and dead. In addition, the cohort was at risk of four different fracture events. These were wrist or other fracture, hip fracture, vertebral fracture, and second hip fracture. It was assumed that risendronate was effective during the therapy, without any residual effect.
Outcomes assessed in the review The health outcomes assessed from the published studies were:
the relative risk reductions for hip, vertebral and other fractures with risendronate therapy;
the fracture risk in an untreated population;
the incidence of hip fracture; and
the disutility values of hip, vertebral and wrist fractures.
Study designs and other criteria for inclusion in the review The risendronate efficacy data were mainly obtained from randomised controlled trials.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies The use of data from randomised controlled trials ensured the validity of one of the primary studies.
Methods used to judge relevance and validity, and for extracting data Number of primary studies included The effectiveness data were derived from four primary studies.
Methods of combining primary studies The studies were combined using a narrative method.
Investigation of differences between primary studies Results of the review The relative risk reductions with risendronate therapy were:
for hip fracture, 60% (95% confidence interval, CI: 20 - 80);
for vertebral fracture, 41% (95% CI: 18 - 58); and
for other fractures, 39% (95% CI: 6 - 61).
The incidence of hip fracture was 2.57%, although it was 2.48% in the original study.
The disutility values were:
for hip fracture, 0.264 (95% CI: 0.2163 - 0.311);
for vertebral fracture, 0.08 (95% CI: 0.059 - 0.101); and
for wrist fracture, 0.025.
The fracture risk in an untreated population was unclear.
Measure of benefits used in the economic analysis The benefit measure used in the economic analysis was the QALY, which was obtained by modelling. The QALYs were discounted at a rate of 1.5%. The disutility of hip fracture was estimated by comparing the values for a measure of utility using the EuroQoL from patients who had sustained a fracture (Iglesias, unpublished data).
Direct costs A 6% discount rate was used, as the lifetime costs were calculated in the analysis and the time horizon of the study was longer than 2 years. The unit costs were reported, but the quantities of resources used were not. The economic evaluation included the costs of risendronate therapy, general practitioner (GP) consultations, bone mineral density scan, and the treatment of hip, vertebral and wrist fractures. The authors assumed that prescribing risendronate would lead to one extra visit to the GP. The cost/resource boundary adopted in the analysis was not stated. The total costs were calculated using modelling. The costs were estimated from published studies. The source of the resource use data was not stated. The price year was 1999.
Statistical analysis of costs Ranges of the costs were reported, but statistical analyses of the costs were not performed in the base-case.
Indirect Costs The indirect costs were not included.
Sensitivity analysis A Monte Carlo simulation exercise was conducted to deal with uncertainty. With the exception of the cost of risendronate, all the effectiveness and cost variables used in the model were varied. Two standard (one-way) sensitivity analyses were performed and the cost-effectiveness ratio was calculated. The first analysis was conducted over a follow-up period of 3 years, which was the length of the study used to provide data on risendronate efficacy. The second analysis was conducted over a follow-up period of 3 years and using the trial incidence.
Estimated benefits used in the economic analysis In the undiscounted scenario, the QALYs gained were 7.376 with no therapy and 7.419 with risendronate therapy, with an increment of 0.043 QALYs.
In the discounted scenario, the QALYs gained were 6.739 with no therapy and 6.778 with risendronate therapy, with an increment of 0.039 QALYs.
Cost results In the undiscounted case, the total lifetime costs per patient were 15,683 with no therapy and 14,897 with risendronate therapy. The cost-savings of 786 favoured risendronate.
In the discounted scenario, the total lifetime costs per patient were 8,888 with no therapy and 8,466 with risendronate therapy. The cost-savings of 422 favoured risendronate.
Synthesis of costs and benefits An incremental cost-utility analysis was performed to combine the costs and benefits of the interventions. In the base-case, the risendronate therapy was dominant over no therapy (less costly and more QALYs). In the first sensitivity analysis (3 years' follow-up), the incremental cost per QALY with risendronate therapy over no therapy was 8,625 in the undiscounted scenario and 1,187.5 in the discounted scenario. In the second sensitivity analysis (3 years' follow-up and trial incidence), the incremental cost per QALY with risendronate therapy over no therapy was 6,235 in the undiscounted scenario, while in the discounted scenario, risendronate was dominant.
Authors' conclusions Risendronate therapy for the prevention of vertebral and non-vertebral fractures among old women with severe established osteoporosis was effective in improving quality-adjusted life-years (QALYs) at a reasonable cost. The cost was well below the benchmark of 20,000 per QALY used in the UK.
CRD COMMENTARY - Selection of comparators The comparator used in the trials was placebo (either no treatment or calcium with vitamin D in the latest trial). Therefore, as the authors noted, it was not entirely pragmatic or reflective of normal practice. The authors stated that risendronate therapy was not compared with other therapies, such as hormone replacement therapy, because of the lack of reliable data on the effectiveness of other interventions. You should decide whether no therapy represents a valid comparator in your own setting.
Validity of estimate of measure of effectiveness The effectiveness analysis used published studies, but a formal review of the literature was not undertaken. It was unclear whether the authors considered the impact of differences in the primary studies when assessing the effectiveness. The basic estimates were combined using narrative methods. The effectiveness estimates were treated stochastically. The authors pointed out the relative merits of using trial data in their model as "it is likely that patients enrolled in a clinical trial are less frail than the 'average' high risk patient seen in normal practice, and will have a lower absolute risk of fracture". The estimated hip fracture rate used (2.75%) was higher than the relevant trial rate (2.48%). The authors accounted for this in terms of the "healthy cohort" effect on trial patients. The state transition probabilities used in the Markov model were not reported in the paper, thus making it difficult to assess their validity.
Validity of estimate of measure of benefit QALYs were used as the benefit measure in the economic analysis, using EuroQoL estimates and unpublished data from the author. More information would have been useful in making an objective assessment of the validity of the QALY data used in the model, which was unpublished. Appropriate discounting and modelling were performed. The use of QALYs enhances the comparability of the benefits of the study treatment with those of other interventions funded in the health care system.
Validity of estimate of costs The perspective adopted in the study was not explicitly stated. Thus, it was unclear whether all the relevant categories of costs were included in the analysis. The price year was reported and discounting was performed. Sensitivity analyses were conducted to take into account the uncertainty around the cost estimates. The unit costs were reported. The quantities of resources used were estimated on the basis of the authors' assumptions, as concurrent cost analyses were not available from the trial data. The cost estimates may, therefore, need to be treated with a degree of caution.
Other issues The authors did not compare their findings with those from other studies. The issue of the generalisability of the study results to other settings was addressed through sensitivity analyses. However, it should be noted that the study population was older (over 75 years) than those affected by osteoporosis (60 years or older). The cost-effectiveness in younger women would not be as favourable as suggested by the present results. It should also be noted that the period of follow-up in the modelling (25 years from age 75) would take patients well beyond their natural life expectancy when death could be caused by other, unrelated conditions. As such, this may not be a realistic approach to adopt in the model. The authors reported some limitations of the study. First, the cost data were not derived from the effectiveness data trial. Second, the trial was placebo-controlled, and hence, not entirely pragmatic. The authors also highlighted that the choice of hip fracture as an outcome rather than a surrogate measure represented a strength of their analysis.
Implications of the study The main implication of the study is that, within the caveats highlighted, risendronate therapy is a cost-effective treatment for the secondary prevention of vertebral and non-vertebral fractures among women with severe osteoporosis.
Source of funding Supported by Procter and Gamble Pharmaceuticals and Aventis Pharma.
Bibliographic details Iglesias C P, Torgerson D J, Bearne A, Bose U. The cost utility of bisphosphonate treatment in established osteoporosis. QJM 2002; 95(5): 305-311 Indexing Status Subject indexing assigned by NLM MeSH Aged; Calcium Channel Blockers /economics /therapeutic use; Cost-Benefit Analysis; Etidronic Acid /analogs & Female; Hip Fractures /prevention & Humans; Models, Econometric; Osteoporosis, Postmenopausal /drug therapy; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risedronate Sodium; Time Factors; control; derivatives /economics /therapeutic use AccessionNumber 22002000848 Date bibliographic record published 30/06/2003 Date abstract record published 30/06/2003 |
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