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Cost-effectiveness of risedronate for the treatment of osteoporosis and prevention of fractures in postmenopausal women |
Kanis J A, Borgstrom F, Johnell O, Jonsson B |
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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 risedronate, for the treatment of osteoporosis and prevention of fractures in postmenopausal women.
Type of intervention Treatment and primary prevention.
Economic study type Cost-effectiveness analysis and cost-utility analysis.
Study population The study population comprised a hypothetical cohort of postmenopausal women aged between 60 and 80 years old, with or without prior vertebral fractures, and with bone mineral density (BMD) score known or unknown.
Setting The setting was primary and secondary care. The economic study was carried out in the UK.
Dates to which data relate The effectiveness data were derived from studies published between 1999 and 2001. The resource use data were collected between 1996 and 2002. The price year was 2000/01.
Source of effectiveness data The effectiveness data were derived from a review or synthesis of studies.
Modelling A Markov model was constructed to evaluate the lifetime risk of fracture, costs and benefits of the treatment. The cycle length was 1 year, with patients being followed up until they were 100 years old or dead.
Outcomes assessed in the review The main outcomes estimated from the literature were:
the population fracture incidence (i.e. hip and forearm fracture incidence and vertebral fracture incidence);
the relative risk (RR) of fracture, obtained according to BMD at the femoral neck and the presence or absence of a prior vertebral fracture; and
the fracture risk reduction with risedronate.
Study designs and other criteria for inclusion in the review Not stated. The effectiveness evidence, however, was derived from three large, double-blind, placebo-controlled phase III trials plus evidence on different fracture incidences from the UK and other European studies. Given the limited UK data available, the authors reviewed relevant Western Europe studies.
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 nine primary studies were included as sources of effectiveness evidence. Estimates of vertebral fracture risk were based on data from a Rotterdam study and the European Prospective Osteoporosis study. The relationship between BMD score and fracture risk and between prior vertebral fracture and subsequent fractures were taken from published meta-analyses.
Methods of combining primary studies The treatment effect, measured as relative fracture risk reduction, was derived from an original meta-analysis of three randomised controlled trials. A logistic regression and a Poisson model were fitted to the incidence data to obtain the exponential risk of fracture for age.
Investigation of differences between primary studies Results of the review For hip fracture, the RR reduction with risedronate was 43% (RR 0.57, 95% confidence interval, CI: 0.41 - 0.79).
For vertebral fractures, the RR reduction was 37% (RR 0.63, 95% CI: 0.53 - 0.76).
For forearm fractures, the RR reduction was 22% (RR 0.78, 95% CI: 0.68 - 0.91).
For women with a prior spine fracture, the risk of a forearm fracture was 1.4 (95% CI: 1.2 - 1.7), a spine fracture 4.4 (95% CI: 3.6 - 5.4) and a hip fracture 2.3 (95% CI: 2.0 - 2.8).
The RRs for different types of fracture at a specific age were adjusted according to BMD (at the threshold of osteoporosis, T-score = -2.5 SD, with a score <= 2.5 SD or unknown) and the presence or absence of a prior vertebral fracture (full details provided in the paper). These data formed the main outcome drivers used in the model. The results were only reported for the base-case of a woman aged 70 years.
Measure of benefits used in the economic analysis The measure of benefits used was the quality-adjusted life-years (QALYs). The authors adopted the quality of life values the year after osteoporotic fracture from a Swedish study. Quality of life before fracture, and after the first year following fracture, was based on assumptions. Utility values for different fractures in the UK were obtained using social tariff values for age in the general UK population. The QALYs were discounted at a rate of 1.5%, as recommended by the National Institute for Clinical Excellence (NICE).
Direct costs The health service costs were reported. Both the cost of the intervention and the cost of treating the fractures were included. The key resource use categories were drug acquisition costs, annual monitoring costs (i.e. physician visits, BMD measurement), and the costs of treating fractures during the acute phase and long-term maintenance, weighted by age. Resource use was only partially reported separately from the costs. The costs were discounted at a rate of 6%, following NICE guidelines.
Statistical analysis of costs No statistical analysis of the costs was reported.
Indirect Costs The indirect costs were not included.
Sensitivity analysis The 95% CIs of the RR reduction of fractures with risedronate were used as the worst- and best-case scenarios for a sensitivity analysis on treatment efficacy. A key assumption of the model, the maintenance of benefit after treatment stopped, was also examined with variations between 0 and 15 years. Also, estimates of additional risk factors independent of BMD were used in the sensitivity analysis, such as history of oral glucocorticoid use and smoking for women with no prior fracture and at a threshold of osteoporosis. Other secondary sensitivity analyses included variation of the discount rate for benefits, increasing the mortality risk in the first year of fracture, decreasing the utility loss associated with vertebral fractures, and changes in the RR for various fracture types.
Estimated benefits used in the economic analysis For the base-case age of 70 years, the strategy of treating a woman with a prior vertebral fracture generated a 0.063 QALY gain if the BMD T-score was -2.5 SD, but a QALY loss was observed if the BMD T-score was <= -2.5 SD.
In the case of no prior vertebral fracture, the treatment strategy generated a 0.028 QALY gain if the BMD T-score was -2.5 SD and 0.052 if the BMD T-score was <= -2.5 SD.
Cost results For the base-case age of 70 years, the costs associated with the strategy of treating a woman with a prior vertebral fracture ranged from 6,249 to 10,674, depending on their BMD score, compared with 5,595 to 10,471 for the no treatment option. In other words, incremental costs of 653 and 203, respectively.
In the case of no prior vertebral fracture, the costs associated with the treatment strategy ranged from 3,870 to 6,069, compared with 2,718 to 5,373 for the no treatment option (i.e. incremental costs of 1,152 and 696, respectively).
Synthesis of costs and benefits The cost-effectiveness results were calculated in a deterministic manner. They were interpreted using a willingness-to-pay ratio of 30,000 per QALY gained. For the base-case age of 70 years, the results showed that the intervention with risedronate was cost-effective in women who had a prior fracture, with a BMD T-score at the threshold of osteoporosis (i.e. T = 2.5 SD), and in women with no prior fracture and BMD T-score <= 2.5. The incremental cost-effectiveness ratios (ICERs) were 10,363 per QALY gained and 13,490 per QALY gained, respectively.
Treatment with risedronate was dominated in the case of women with prior spine fracture and T-score <= 2.5, and showed an ICER of 40,617 per QALY gained in the case of no prior vertebral fracture with a BMD T-score at the threshold of osteoporosis.
Results of the sensitivity analyses suggested that, even with no maintenance of benefits after treatment withdrawal, the cost-effectiveness results were not qualitatively different. Increasing the maintenance of benefits to 10 and 15 years resulted in risedronate therapy becoming cost-effective for all clinical scenarios at the base-case age of 70. Also, where an additional risk was assumed, the intervention became cost-effective at age 80.
Authors' conclusions Compared with no treatment, risedronate was cost-effective for patients with established osteoporosis and a history of fracture (incremental cost-effectiveness ratio, ICER=10,363, base-case age 70 years). This was true over the entire age range (60 to 80 years). These results withstood the sensitivity analysis.
CRD COMMENTARY - Selection of comparators The authors justified the fact that they did not undertake a comparison with standard or alternative treatments on the grounds that no comparative studies of efficacy were available. You should decide whether the option of no treatment represents a valid comparator in your own setting.
Validity of estimate of measure of effectiveness The effectiveness estimates were derived from appropriate sources, although it was unclear whether a systematic search of the literature was undertaken as no details were provided in the paper. The authors clearly reported the methods used to combine the evidence. All assumptions were clearly reported and seem sensible, and the ranges used appear to have been appropriate. The authors discussed the limitations around the assumptions they made in the model.
Validity of estimate of measure of benefit The estimation of benefits was obtained from the decision model. Although the sources for utility values and related assumptions were clearly reported, a summary table with Swedish values and their adjustment to the UK social tariff, as well as the adjustment for different types of fracture, would have helped in clarifying the final values used.
Validity of estimate of costs The authors explicitly stated the perspective adopted in the analysis. However, it was unclear whether all the categories of costs relevant to the perspective adopted were included in the analysis. Direct costs such as acute treatment of fractures were based on published estimates, but there was no further description of the costs included under this category. The costs for the second and following years after a fracture were based only on assumptions.
Other issues The authors discussed their results in comparison with other relevant studies and current practice guidelines. This was particularly so for the utility estimates for the model. They also addressed the issue of generalisability, expressing caution in applying the results to other countries because of a worldwide variation in fracture risk. The results appear to have been deterministic, but this was not explicitly stated in the report. There was degree of inconsistency about the relevance or irrelevance of the BMD T-scores, in terms of their impact on the cost-effectiveness results, between the cost-effectiveness results reported in table 3 and the authors' interpretation in the text. The authors appropriately discussed their assumptions, and the strengths and limitations of their study.
Implications of the study The authors believed that their results indicate that pharmacological-intervention thresholds should be based on fracture risk (assessed by multiple factors including BMD T-score, fracture history and age) rather than on BMD alone. By assessing additional fracture risk factors, the authors have identified new sub-group populations for whom risedronate could be a cost-effective treatment.
Bibliographic details Kanis J A, Borgstrom F, Johnell O, Jonsson B. Cost-effectiveness of risedronate for the treatment of osteoporosis and prevention of fractures in postmenopausal women. Osteoporosis International 2004; 15(11): 862-871 Other publications of related interest Reginster J, Minne HW, Sorensen OH, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenoupausal osteoporosis. Osteoporosis International 2000;11:83-91.
Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and non vertebral fractures in women with postmenopausal osteoporosis: a randomised controlled trial. JAMA 1999;282:1344-52.
McClung MR, Geusens P, Miller PD, et al. Effect of risedronate on the risk of hip fracture in elderly women. New England Journal of Medicine 2001;344:333-40.
Indexing Status Subject indexing assigned by NLM MeSH Aged; Aged, 80 and over; Bone Density; Calcium Channel Blockers /therapeutic use; Cost-Benefit Analysis; Etidronic Acid /analogs & Female; Humans; Middle Aged; Osteoporosis, Postmenopausal /drug therapy /economics /mortality; Randomized Controlled Trials as Topic; Risedronate Sodium; Risk Factors; Spinal Fractures /prevention & Treatment Outcome; control; derivatives /therapeutic use AccessionNumber 22004001403 Date bibliographic record published 31/12/2005 Date abstract record published 31/12/2005 |
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