|
The cost-effectiveness of therapy with teriparatide and alendronate in women with severe osteoporosis |
Liu H, Michaud K, Nayak S, Karpf D B, Owens D K, Garber A M |
|
|
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 study examined three treatment strategies for postmenopausal women with severe osteoporosis:
usual care (UC) based on calcium or vitamin D plus 5 years of alendronate therapy (alendronate alone);
UC plus 2 years of teriparatide therapy (teriparatide alone); and
UC plus 2 years of teriparatide therapy followed by 5 years of alendronate therapy (sequential teriparatide/alendronate).
The alendronate-alone strategy consisted of alendronate sodium, 10 mg/day, for 5 years. The teriparatide-alone strategy consisted of teriparatide, 20 microg/day subcutaneously, for 2 years. For sequential teriparatide/alendronate, 2 years of teriparatide (20 microg/day) was followed by 5 years of alendronate (10 mg/day).
Study population The study population comprised a hypothetical cohort of postmenopausal white women with severe osteoporosis, defined by low bone mass (base case, femoral neck bone mineral density (BMD) T score of -2.5) and pre-existing vertebral fracture.
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 1995 and 2005. No dates for resource use were clearly reported. The price year was 2003.
Source of effectiveness data The effectiveness evidence was derived from a synthesis of published studies and authors' opinions.
Modelling A cost-effectiveness model (probably, a Markov model) was constructed to compare UC with UC plus three treatment strategies in a hypothetical 70-year-old woman with severe osteoporosis. The model incorporated morphometric (i.e. radiologic) vertebral and clinical vertebral, hip and wrist fractures. The authors stated that the model considered 6 key elements. These were chosen treatment strategy, fracture state, survival during cycle, entrance to nursing home, new fracture occurrence, and adverse events from medication. The time horizon of the model was lifetime and 3-month cycles were used. Other details of the model were not reported. The model incorporated mild hypercalcaemia and osteosarcoma (teriparatide) and oesophagitis and oesophageal ulceration (alendronate) as possible adverse events from active therapy. The authors stated that much of the information on clinical and economic data could be found in an online technical appendix (although at the time this abstract was written, access to that site was impossible).
Outcomes assessed in the review The outcomes estimated from the literature were data on morbidity and mortality, risk of fracture, adverse events, utility values and nursing home variables.
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. The data came from multiple sources, including clinical trials and observational studies. Limited information on the design and patient characteristics of the primary studies was provided. The fracture risk for women with osteoporosis was taken from a large US observational study. Health state utilities were obtained from studies that applied time trade-off or standard gamble methods. The mortality rates were derived from US age-stratified mortality tables.
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 Twenty-six primary studies provided the clinical data used in the decision model.
Methods of combining primary studies Investigation of differences between primary studies Results of the review Future fracture risk for women with osteoporosis was estimated by means of a logistic regression based on age, BMD and prior fractures. Fracture rates with the three strategies under analysis were obtained by superimposing the relative risk for each treatment to the general fracture rate for women with osteoporosis.
For the alendronate-alone strategy, the relative risks for vertebral, hip and wrist fractures while receiving therapy were 0.53, 0.49 and 0.52, respectively. Fracture risk returned to UC rates in a linear fashion over 5 years after cessation of alendronate therapy.
For the teriparatide-alone strategy, the relative risks for vertebral, hip and wrist fractures while receiving therapy were 0.35, 0.47 and 0.47, respectively. The fracture relative risks remained constant during the 2 years of teriparatide treatment. On cessation of teriparatide treatment, fracture risk returned to UC rates in a linear fashion over 5 years.
For sequential teriparatide/alendronate therapy, the relative risks for vertebral, hip and wrist fractures while receiving therapy were 0.35, 0.47 and 0.47, respectively, with teriparatide and 0.19, 0.23 and 0.24 for subsequent treatment with alendronate.
Clinical vertebral fractures accounted for 35% of morphometric vertebral fractures. Patients who experienced osteosarcoma or oesophageal ulceration discontinued therapy. Patients who experienced gastrointestinal discomfort or hypercalcaemia received treatment for these conditions and continued therapy.
The health state utility for a condition of osteoporosis without fracture was age-dependent. It was:
0.829 for women aged 60 - 64 years,
0.806 for women aged 65 - 69 years,
0.747 for women aged 70 - 74 years,
0.731 for women aged 75 - 79 years,
0.699 for women aged 80 - 84 years, and
0.676 for women aged 85 years or older.
The health state utility for a hip fracture was 0.797 in the first year and 0.9 in subsequent years (multiplier).
The health state utility for a vertebral fracture was 0.82 in the first year and 0.931 in subsequent years (multiplier).
The health state utility for a wrist fracture was 0.981 in the first year and 1.0 in subsequent years (multiplier).
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 Compliance was 100%. There was no additional fracture reduction benefit with UC (calcium or vitamin D supplementation). No cases of osteosarcoma occurred. For the sequential teriparatide/alendronate strategy, it was assumed that alendronate would decrease fracture risk in the same proportion as it would in a treatment-naive patient.
Measure of benefits used in the economic analysis The summary benefit measure used was the expected number of quality-adjusted life-years (QALYs). These were estimated by combining the utility weights and life expectancy in the decision model. The QALYs were discounted at an annual rate of 3%.
Direct costs Although the authors stated that a societal perspective was adopted, only direct medical costs were included in the base-case (given that the patients were older than 70 years). A detailed breakdown of the cost items was not provided, but macro-categories of costs were considered. These were alendronate, teriparatide, medical services, treatment of fractures and nursing home expenses. The unit costs were not presented separately from the quantities of resources used (although further information may be obtainable from a technical appendix, which was not accessible at the time this abstract was written). The sources of resource use were unclear. The drug costs were derived from wholesale prices listed in the Drug Topic Red Book, while the costs of medical services and fractures were mainly obtained from Medicare sources. Nursing home costs were estimated using an insurance survey. Discounting was relevant, as the lifetime costs were included, and an annual rate of 3% was applied. The price year was 2003.
Statistical analysis of costs Statistical analyses of the costs were not reported.
Indirect Costs Indirect costs were not considered in the base-case because of the age of the patients.
Sensitivity analysis Sensitivity analyses were carried out to assess the robustness of the cost-utility ratios to variations in the model inputs. Specifically, the authors varied the duration of efficacy after cessation of teriparatide. Two alternative assumptions about the efficacy of alendronate therapy following teriparatide were also made. The first one assumed that alendronate only maintained the antifracture benefits accrued while receiving teriparatide therapy, while the second one assumed that it completely eliminated fractures. The authors also varied the cost of alendronate and teriparatide, BMD, age, teriparatide treatment length, compliance and other variables. Indirect costs and annual medical expenditures were also considered. Some alternative values were based on published data, while others were set by the authors. It is likely that sensitivity analyses were based on first-order Monte Carlo simulations, although this was not explicitly reported.
Estimated benefits used in the economic analysis The expected QALYs were reported in graphical format only. Sequential teriparatide/alendronate was the strategy with the highest QALY gains, followed by alendronate alone, teriparatide alone and UC.
Cost results The estimated costs were reported in graphical format only. Sequential teriparatide/alendronate was the most costly strategy, followed by teriparatide alone, alendronate alone and UC.
Synthesis of costs and benefits Incremental cost-utility ratios were calculated in order to combine the costs and benefits of the alternative strategies.
The incremental cost per QALY gained with alendronate alone compared with UC was $11,600. The incremental cost per QALY gained with sequential teriparatide/alendronate relative to alendronate alone was $156,500. Teriparatide alone was dominated because it was more expensive and produced a smaller increase in QALYs compared with alendronate alone. However, in women in whom alendronate use was not feasible, teriparatide alone cost $172,300 per QALY relative to UC.
The sensitivity analysis showed that the base-case results were quite robust to variations in clinical and economic assumptions. Teriparatide alone was less cost-effective than alendronate even if its efficacy lasted 15 years after treatment cessation. Further, sequential teriparatide/alendronate therapy was less cost-effective than alendronate even if fractures were eliminated during the alendronate phase. The cost-effectiveness of sequential teriparatide/alendronate therapy was less than $50,000 per QALY (compared with alendronate alone) if the price of teriparatide decreased 60%, if used in elderly women with T scores of -4.0 or less, or if 6 months of teriparatide therapy had comparable efficacy to 2 years of treatment.
Authors' conclusions Alendronate therapy was a cost-effective alternative to UC for postmenopausal women with severe osteoporosis in the USA. Therapy with teriparatide alone was more expensive and produced a smaller increase in quality-adjusted life-years (QALYs) than therapy with alendronate. Sequential teriparatide/alendronate therapy was an expensive treatment option, but could become more cost-effective under specific conditions, such as reductions in teriparatide price or if its use was restricted to exceptionally high-risk women. The high cost of teriparatide explained the high cost-utility ratios observed in both the base-case and sensitivity analysis.
CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparators was appropriate since teriparatide, a recently available anabolic agent for the treatment of osteoporosis, and alendronate, a widely used treatment, were compared with UC, which represents a strategy of no treatment. The dosages were accurately reported. The authors stated that the model did not evaluate raloxifene hydrochloride, a potential comparator, because it appeared to be less effective than alendronate in reducing fractures. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness The effectiveness evidence might have been derived from selectively identified studies, as no details of the methods and conduct of a systematic review of the literature were reported. Further, three was limited information on the design and other characteristics of the primary studies. Thus, the validity of the primary sources could not be assessed. The methods used to extract and combine the primary estimates were not described, and the issue of heterogeneity across primary studies was not addressed. The robustness of the study conclusions to variations in clinical estimates was extensively investigated in the sensitivity analysis, which identified key model inputs.
Validity of estimate of measure of benefit QALYs were an appropriate benefit measure because they capture the impact of the intervention on both quality of life and survival, which are relevant dimensions of health for patients with osteoporosis. Different instruments were used to derive utility weights from the literature. The use of QALYs enables comparisons to be drawn with the benefits of other health care interventions. Discounting was applied, as recommended by US guidelines.
Validity of estimate of costs The analysis of the costs was carried out from a societal perspective, but the indirect costs were only taken into account in the sensitivity analysis. This is because productivity losses associated with osteoporosis would be small for the patients considered in the analysis, owing to the advanced age of women with severe osteoporosis (70 years in the base-case analysis). The unit costs were not presented separately from the resource quantities, and most costs were presented as macro-categories. The price year was reported, which will assist reflation exercises in other settings. Discounting was relevant and was appropriately applied. The impact of using alternative discount rates was not investigated. Statistical analyses of the costs were not performed, but the use of different cost estimates was tested in the sensitivity analysis, where the potential inclusion of annual health care costs and indirect costs was investigated.
Other issues The authors stated that their analysis corroborated the findings from previous studies that had proven the cost-effectiveness of alendronate for women with severe osteoporosis. For teriparatide, the current results were consistent with a study carried out in the UK, but conflicted with the results from a Swedish study, which was industry-sponsored and did not consider alendronate as a relevant comparator. The issue of the generalisability of the study results to other countries was not explicitly addressed, but the extensive sensitivity analysis enhances the external validity of the study. The results of the sensitivity analyses were extensively reported, although the estimated costs and benefits of the alternative strategies were not. More information on clinical and economic inputs, as well as the results of the study, can probably be found in the technical appendix (this was not accessible online at the time this abstract was written).
The authors noted some limitations of their analysis. First, the study referred to treatment-naive women and may not, therefore, be applicable to patients receiving treatment for osteoporosis. Second, assumptions about the effectiveness of teriparatide were explicitly biased in order to favour the drug under investigation, although teriparatide remained not cost-effective. In effect, quality of life decrements for daily subcutaneous injection of teriparatide were not considered. Third, the analysis considered daily doses of teriparatide, but the results should also be valid for weekly administration. Fourth, the results of the analysis might be applicable to risedronate sodium, which has a cost profile similar to that of alendronate.
Implications of the study The study results did not support the use of teriparatide for the treatment of severe osteoporosis in postmenopausal women, but they did confirm the cost-effectiveness of alendronate.
Source of funding Supported by the Agency for Healthcare Research and Quality, and the Department of Veterans Affairs.
Bibliographic details Liu H, Michaud K, Nayak S, Karpf D B, Owens D K, Garber A M. The cost-effectiveness of therapy with teriparatide and alendronate in women with severe osteoporosis. Archives of Internal Medicine 2006; 166: 1209-1217 Other publications of related interest Stevenson M, Lloyd Jones M, De Nigris E, et al. A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis. Health Technol Assess 2005;91-160.
Lundkvist J, Johnell O, Cooper C, Sykes D. Economic evaluation of parathyroid hormone (PTH) in the treatment of osteoporosis in postmenopausal women. Osteoporos Int 2006;17:201-11.
Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001;344:1434-41.
Indexing Status Subject indexing assigned by NLM MeSH Aged; Alendronate /economics /therapeutic use; Bone Density Conservation Agents /economics /therapeutic use; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Humans; Osteoporosis /drug therapy /economics; Severity of Illness Index; Teriparatide /economics /therapeutic use AccessionNumber 22006008255 Date bibliographic record published 31/12/2006 Date abstract record published 31/12/2006 |
|
|
|