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Potential cost-effective use of spine radiographs to detect vertebral deformity and select osteopenic post-menopausal women for amino-bisphosphonate therapy |
Schousboe J T, Ensrud K E, Nyman J A, Kane R L, Melton L 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 Three strategies for the treatment of osteopenic postmenopausal women were examined. The strategies were:
5 years of amino-bisphosphonate (alendronate) therapy for all (Rx all);
5 years of alendronate therapy for only those women with a prevalent radiographic vertebral deformity (Rx/X-ray); and
no alendronate treatment (no Rx).
Study population The study population comprised a hypothetical cohort of osteopenic postmenopausal women. Osteopenia was defined as a T-score of -1.0 to -2.4.
Setting The setting was secondary care. The economic study was carried out in the USA.
Dates to which data relate The effectiveness data were derived from studies published between 1982 and 2004. The costs and some resource use data were derived from studies published between 2001 and 2003. The price year was 2001.
Source of effectiveness data The effectiveness evidence was derived from a synthesis of completed studies and authors' opinions.
Modelling A Markov model was constructed to compare the three strategies under examination in a hypothetical cohort of osteopenic postmenopausal women. Women in each of the three treatment arms (Rx all, Rx/X-ray or no Rx) of the model were stratified into two further arms, those with and those without a prevalent vertebral deformity. In all strategies, if an incident fracture occurred, alendronate therapy was started (or extended) for 5 years. The time horizon of the model was lifetime and the cycle length was 6 months. The eight health states considered were no fracture, post distal forearm fracture (DFF), post clinical vertebral fracture, post radiographic vertebral fracture, post hip fracture, post other fractures (proximal forearm, humerus, scapula, clavicle, sternum, ribs, pelvis, distal femur, patella, tibia, or proximal fibula), post hip and vertebral fracture, and death. Beginning in the no fracture state, women could develop a fracture at which time transition to that post facture state occurred.
Outcomes assessed in the review The outcomes estimated from the literature were:
the probabilities of fractures,
the relative risk (RR) of vertebral fracture on drug therapy,
mortality, and
the quality-adjusted life-years (QALYs) associated with each health state.
Study designs and other criteria for inclusion in the review It was unclear whether a systematic review of the literature was undertaken to identify the primary studies, which may therefore have been identified selectively. Mortality data were derived from US life statistics. Some probabilities of fractures came from comprehensive population-based age-specific data for women from the Rochester Epidemiology Project. Calculations of BMD-specific fracture risk were extensively described in an appendix. Alendronate effectiveness was obtained from a clinical trial. Details of the calculation of QALYs were not reported, but utility values used to populate the model health states were obtained from five different studies.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Specific criteria were not used to ensure the validity of the primary studies. However, data from a clinical trial was used to derive alendronate effectiveness, which was appropriate as this type of study design is usually robust.
Methods used to judge relevance and validity, and for extracting data Number of primary studies included Fourteen primary studies provided the clinical data.
Methods of combining primary studies Investigation of differences between primary studies Results of the review Femoral neck BMD decreased by 0.00554 gm/cm2 per year.
The probabilities of clinically silent prevalent radiographic vertebral deformity were stratified by age and BMD T-scores. For women aged 60, these ranged from 0.08 for a femoral neck T-score of -1 to 0.16 for a femoral neck T-score. Corresponding values ranged from 0.10 to 0.21 for women aged 65, from 0.13 to 0.26 for women aged 70, from 0.16 to 0.32 for women aged 75, and from 0.20 to 0.38 for women aged 80.
The RRs of hip, vertebral, DFF and other fractures for each Z-score change of 1 were 2.6, 1.8, 1.4, and 1.6, respectively.
To further adjust the risk of fracture for the presence or absence of one or more prevalent vertebral deformities, RRs of 4.1 (vertebral), 1.8 (hip), 1.0 (DFF) and 1.6 (other) for incident fractures were considered among women with one or more prevalent vertebral deformities compared with those without prevalent deformity.
Also considered was an RR of 4.1 for a subsequent clinical vertebral fracture following an incident vertebral fracture, an RR of 1.7 for a subsequent hip fracture following an incident hip fracture, and an RR of 2.1 for a subsequent DFF following an incident DFF.
The RR of clinical and radiographic vertebral fractures was 0.5 while on alendronate therapy.
The mortality associated with acute hip fracture was 1.375 times the base rate.
The QALYs for the first year after fracture and in subsequent years were, respectively:
0.84 and 0.84 for the state of no fracture;
0.82 and 0.839 for the state of post DFF;
0.753 and 0.813 for the state of post other fracture;
0.67 and 0.68 for the state of post hip fracture;
0.58 and 0.76 for the state of post clinical vertebral fracture;
0.76 and 0.76 for the state of post morphometric vertebral fracture; and
0.41 and 0.60 for the state of post vertebral or hip fracture.
Methods used to derive estimates of effectiveness The authors made some assumptions that were used in the decision model.
Estimates of effectiveness and key assumptions The drug adherence rate was 100%.
The RR for non-vertebral fractures while on alendronate therapy compared with no drug therapy was 0.7.
It was further assumed that there was a linear, gradual offset of fracture reduction benefit over the subsequent 5 years following treatment discontinuation.
Measure of benefits used in the economic analysis The summary benefit measure used was the expected number of QALYs. This was estimated using a modelling approach based on published evidence. An annual discount rate of 3% was applied.
Direct costs The analysis of the costs was carried out from a societal perspective. The direct medical costs included were for alendronate, treatment of fractures, physician visits, baseline thoracic and lumbar lateral spine radiographs, bone densitometry, and long-term care following a fracture. The costs associated with side effects of alendronate were negligible and were not included in the model. The unit costs were not presented separately from the quantities of resources used. The cost of alendronate was based on average wholesale prices. The costs of fractures were estimated from a study published in 2002. Other costs came from Medicare reimbursement rates. The costs and resources for long-term care post fracture came from studies published in 2002 and 2003. The sources used to derive resource use for some items were not reported. The price year was 2001. Discounting was relevant, as a lifetime horizon was used in the model, and an annual rate of 3% was applied.
Statistical analysis of costs The costs were treated deterministically.
Indirect Costs The indirect costs were, appropriately, included as a societal perspective was adopted. The quantities of resources (i.e. the proportions of a year with lost productivity for different fractures) were obtained from a published source. The costs were estimated from mean yearly earnings for employed white women in the USA, adjusted by the workforce participation rate which was a function of age. Some details on the unit costs and resource consumption were reported. As in the analysis of the direct costs, an annual discount rate of 3% was applied and 2001 prices were used.
Sensitivity analysis Several univariate sensitivity analyses were carried out to assess the robustness of cost-utility ratios to variations in the model inputs. The inputs varied included fracture costs, fracture rates, disutility attributable to fractures, discount rate, RR of non-vertebral fractures on alendronate, risk of incident fractures attributable to prevalent radiographic vertebral deformity, duration of drug therapy, offset of fracture reduction benefit after drug discontinuation, and non-adherence. The women were stratified according to whether or not they had a maternal history of fracture. A secondary analysis with no additional treatment following incident fractures was also conducted, to assess the effect of this aspect of the model on the cost-utility ratios. A probabilistic sensitivity analysis was also carried out using Monte Carlo simulations.
Estimated benefits used in the economic analysis The expected benefits were not reported.
Cost results The estimated costs were not reported.
Synthesis of costs and benefits Incremental cost-utility ratios were calculated to combine the costs and QALYs of the strategies examined in the study.
The model was run for 12 different combinations of starting age (60, 70 and 80) and femoral neck T-score (-1.0, -1.5, -2.0 and -2.5).
The incremental cost per QALY gained for the Rx/X-ray strategy compared with no intervention (no Rx) ranged from a minimum of $4,150 in women aged 80 with a T-score of -2.4 to $61,192 for women aged 60 with a T-score of -1.0.
The incremental cost per QALY gained for the Rx all strategy compared with no Rx ranged from a minimum of $30,429 for women aged 70 with a T-score of -2.4 to $117,077 for women aged 80 with a T-score of -1.0.
The incremental cost per QALY gained for the Rx all strategy compared with the Rx/X-ray strategy ranged from a minimum of $37,482 for women aged 70 with a T-score of -2.4 to $166,219 for women aged 80 with a T-score of -1.0.
The authors noted that the comparison between the Rx/X-ray and no Rx strategies represented the cost-effectiveness of alendronate therapy on those with prevalent vertebral deformities, while the comparison between the Rx all and Rx/X-ray strategies represented the cost-effectiveness of alendronate therapy on those without documented prevalent vertebral deformities. The comparison between Rx all and no Rx strategies represented the cost-effectiveness of alendronate in treating all women without investigating the existence of vertebral deformities.
Using a threshold of $50,000 per QALY gained, treatment of all women (without spine radiograph) was cost-effective for women with a femoral neck score of -2.0 or lower. While the cost-utility ratios for women with one or more vertebral deformities were significantly lower than those for all women at each combination of age and T-score, the cost-utility ratios for women documented as not having any vertebral deformity were higher than for those estimated for all women.
In a typical 70-year-old woman at different T-scores, alendronate therapy was cost-effective even if treatment reduced the incidence of non-vertebral fractures only slightly. The univariate sensitivity analysis showed that the base-case results were robust to variations in most model inputs. The probabilistic sensitivity analysis suggested that, for a 70-year-old woman, there was a 25% probability that the T-score threshold below which treatment of those with a prevalent vertebral deformity (Rx/X-ray strategy) is cost-effective was higher than -1.0, a 46% possibility that the T-score threshold was lower than -1.5, and a 19% probability that the T-score threshold was lower than -2.0. The results of the secondary analyses confirmed the base-case results.
Authors' conclusions Spine radiography can be used to detect vertebral deformities and select the sub-group of osteopenic, postmenopausal, Caucasian women aged 60 years or older for whom alendronate therapy could be cost-effective.
CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparators was clear since these interventions reflected treatment patterns in the authors' setting. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness The effectiveness evidence was derived from selectively identified studies. It was unclear whether a systematic review of the literature had been performed to identify the primary studies. Only the characteristics of a few primary studies were described. In general it was difficult to assess the validity of the primary sources, with the exception of the clinical trial used to derive data on alendronate efficacy and the population-based study used to assess some fracture rates. The issue of comparability across primary studies was not addressed. Details of the method used to combine the clinical estimates were not reported. Some assumptions were also made on the basis of the authors' experience. Due to uncertainty surrounding some clinical estimates, an extensive sensitivity analysis was carried out.
Validity of estimate of measure of benefit QALYs were the most appropriate benefit measure because they capture the impact of the intervention on both quality of life and survival, which are the most relevant dimensions of health for women at risk of fracture. Few details on the approach used to derive utility adjustments were reported. QALYs are comparable with the benefits of other health care interventions. Discounting was applied, as recommended by economic evaluation guidelines.
Validity of estimate of costs The perspective adopted in the study was explicitly stated. It appears that all relevant categories of costs have been included in the analysis. The use of a societal perspective would seem appropriate given that the disease under study is generally characterised by high indirect costs. A breakdown of cost items was not provided and the unit costs were often presented as macro-categories. Further, limited information on resource use was provided. This limits the possibility of replicating the results in other settings. The source of the data was reported and was consistent with the perspective of the analysis. The method used to calculate the indirect costs was described. The cost estimates were treated deterministically but the impact of variations in some costs was investigated in the sensitivity analysis. The price year was reported, which will facilitate reflation exercises in other time periods.
Other issues The authors did not make extensive comparisons of their findings with those from other studies. They did not explicitly address the issue of the generalisability of the study results to other settings. However, several alternative scenarios were considered in the sensitivity analysis and the use of a stochastic analysis strengthens the external validity of the study. The authors noted some limitations and strengths of the analysis. The key drawbacks of the study were the specific X-ray technique considered in the study, the uncertainty in some clinical estimates, and the use of epidemiological data from a population of Caucasian women residing in the USA. Some advantages of the analysis were the extensive use of sensitivity analyses, the choice of including additional drug therapy following incident fractures in all strategies, and the inclusion of all fractures that could be linked to osteoporosis.
Implications of the study The study results suggested that the use of spinal radiography to detect prevalent vertebral deformity consistent with fracture has the potential to identify osteopenic postmenopausal Caucasian women for which alendronate therapy may be cost-effective. Future studies should determine how accurately spine radiographs can detect vertebral deformity in order to better define T-score ranges over which radiographs are cost-effective.
Source of funding Supported by Hologic Inc., Pfizer Inc., and Eli Lilly and Co.
Bibliographic details Schousboe J T, Ensrud K E, Nyman J A, Kane R L, Melton L J. Potential cost-effective use of spine radiographs to detect vertebral deformity and select osteopenic post-menopausal women for amino-bisphosphonate therapy. Osteoporosis International 2005; 16(12): 1883-1893 Other publications of related interest Cranney A, Wells G, Willan A, et al. Meta-analyses of therapies for postmenopausal osteoporosis. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr Rev 2002;23:508-16.
Johnell O, Jonsson B, Jonsson L, Black D. Cost-effectiveness of alendronate (Fosamax) for the treatment of osteoporosis and prevention of fractures. Pharmacoeconomics 2003;21:305-14.
Black DM, Steinbuch M, Palermo L, et al. An assessment tool for predicting fractures in post-menopausal women. Osteoporos Int 2001;12:519-28.
Indexing Status Subject indexing assigned by NLM MeSH Aged; Aged, 80 and over; Alendronate /economics /therapeutic use; Bone Density Conservation Agents /economics /therapeutic use; Cost-Benefit Analysis /methods; Female; Health Care Costs; Humans; Markov Chains; Middle Aged; Models, Economic; Osteoporosis, Postmenopausal /complications /economics /radiography; Quality-Adjusted Life Years; Spinal Fractures /economics /etiology /prevention & Spine /abnormalities /radiography; control AccessionNumber 22006000067 Date bibliographic record published 30/09/2006 Date abstract record published 30/09/2006 |
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