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Economic evaluation of parathyroid hormone (PTH) in the treatment of osteoporosis in postmenopausal women |
Lundkvist J, Johnell O, Cooper C, Sykes 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 study examined the use of the parathyroid hormone (PTH) teriparatide, in addition to calcium and vitamin D therapy, in postmenopausal women. Teriparatide (rDNA origin) injection (rhPTH (I-34)) was administered as a single daily dose of 20 microg for 18 months. The comparator was the usual calcium and vitamin D therapy.
Study population The hypothetical population comprised a cohort of postmenopausal women with at least one previous vertebral fracture and low bone mineral density (BMD). Since mortality and the risk of a new fracture are higher soon after the fracture, the authors hypothesised that the timing of the treatment intervention would have an effect on the outcome. To explore such a situation, two cohorts of women were considered. These were women who no longer had any increase in mortality and fracture risk because of the previous fracture risk (historic fracture group), and women who had higher mortality and fracture risk during the first years post-fracture (recent fracture group).
Setting The setting for the study was outpatients. The economic study was carried out in Sweden.
Dates to which data relate The effectiveness data used in the model came from studies published between 1993 and 2004. The dates to which the resource use referred were not reported. The price year was 2003.
Source of effectiveness data The clinical data associated with the treatment included:
the efficacy of the intervention, measured as relative risk reductions for vertebral fractures and non-vertebral fragility fractures;
the linear decline of efficacy after treatment cessation;
the age-specific baseline risks of clinical vertebral, hip and wrist fractures;
the risk functions for fracture risks after a previous fracture for the 5 years post-fracture;
the relative risks for each fracture type;
the age-specific normal mortality rates for the general female population; and
the mortality risk functions for the post-fracture period.
Modelling A Markov model was used to follow the course of events when considering multiple clinical fractures. The model was modified from one developed elsewhere (Jonsson et al. 1995 and Zethraeus et al. 2000, see 'Other Publications of Related Interest' below for bibliographic details). The modifications comprised the incorporation of new data on fracture risk and mortality, which considered these risks as being dependent on both age and time since previous fracture, and a reduction in cycle duration (6-month cycles) in order to capture the rapidly changing risks after a previous fracture. The model was analysed using the Monte Carlo technique. It followed the patients from a given age until death or 100 years of age. The health states were reported and a number of modelling assumptions were fully justified. An additional analysis was conducted for back pain and non-vertebral fractures.
Sources searched to identify primary studies Short-term efficacy data were taken from a randomised double-blind placebo-controlled fracture prevention trial (Neer et al. 2001, see 'Other Publications of Related Interest' below for bibliographic details). Long-term risk functions for fracture and mortality were taken from studies of unknown design by Johnell et al. (see 'Other Publications of Related Interest' below for bibliographic details). Age-specific baseline risks were taken from a population-based study (Kanis et al. 2000, see 'Other Publications of Related Interest' below for bibliographic details).
Methods used to judge relevance and validity, and for extracting data The methods used to identify the sources of data used in this study were not described. It may be that the publication of the Neer study motivated this study.
Measure of benefits used in the economic analysis The measures of benefit used were the life-years gained (LYG) and the quality-adjusted life-years (QALYs) gained. Utilities for the general female population were taken from Lundberg 1999 (see 'Other Publications of Related Interest' below for bibliographic details). Acute reduction in health utility after osteoporotic fractures was taken from Zethraeus 2002 (see 'Other Publications of Related Interest' below for bibliographic details). The benefits were discounted at an annual rate of 3%.
Direct costs The direct costs included in the model were the vertebral, hip and wrist fracture costs. These were divided into costs during the year of occurrence and costs during the following years, and were stratified by age. The authors accounted for nursing home care in the cost evaluation in some way for 10% of the patients. The intervention costs included a daily dose of teriparatide with compliance adjustment, an annual physician visit, and a BMD measurement every second year. The costs were discounted at an annual rate of 3%. The price year was 2003. The resource quantities and the unit costs were not reported separately. The costs were adjusted for inflation using the Swedish Consumer Price Index. The costs of calcium and vitamin D were excluded as they were provided in equal doses for both strategies. The costs in added years of life were included in an additional analysis.
Statistical analysis of costs No statistical analyses of the quantities or costs were conducted as the data were deterministic.
Indirect Costs No productivity costs were included.
Currency Euro (EUR). The conversion rate was EUR 1 = SEK 9.2 = US$ 1.3 (2003 values).
Sensitivity analysis Parameter uncertainty was investigated through one-way sensitivity analyses and a probabilistic sensitivity analysis. The parameters analysed through a probabilistic sensitivity analysis were those with a standard deviation available (i.e. treatment efficacy and the acute reduction in health utility in the first year after a fracture). They were assigned prior probability distributions. The authors gave detailed descriptions of the derivation of these distributions and the ranges used.
Estimated benefits used in the economic analysis The effectiveness (QALY) results for a 69-year old population with a T-score of -3 (base-case) were as follows:
7.5852 QALYs for the historic fracture group and 6.1311 QALYs for the recent fracture group with the no teriparatide strategy (calcium and vitamin D only); and
7.6665 QALYs for the historic fracture group and 6.2211 QALYs for the recent fracture group with the teriparatide strategy (calcium and vitamin D plus teriparatide).
The difference between the interventions was 0.081 QALYs for the historic fracture group and 0.090 QALYs for the recent fracture group.
The LYG results were:
11.7278 LYG for the historic fracture group and 10.4911 LYG for the recent fracture group with the no teriparatide strategy (calcium and vitamin D only); and
11.7907 LYG for the historic fracture group and 10.5624 LYG for the recent fracture group with the teriparatide strategy (calcium and vitamin D plus teriparatide).
The difference between the interventions was 0.0629 LYG for the historic fracture group and 0.0713 LYG for the recent fracture group.
Cost results The total costs were:
EUR 33,494 for the historic fracture group and EUR 44,944 for the recent fracture group with the no teriparatide strategy (calcium and vitamin D only); and
EUR 38,713 for the historic fracture group and EUR 46,771 for the recent fracture group with the teriparatide strategy (calcium and vitamin D plus teriparatide).
The difference between the interventions was EUR 5,219 for the historic fracture group and EUR 1,827 for the recent fracture group.
Synthesis of costs and benefits The costs per QALY gained (teriparatide versus no teriparatide) for the treatment of a population of 69-year-olds with a T-score of -3 at the femoral neck were, in the base-case, EUR 20,301 and EUR 64,144 for patients with a recent or a historic vertebral fracture, respectively. If costs in added years of life were included, the results were EUR 37,685 (recent fracture) and EUR 80,251 (historic fracture), respectively.
The authors reported several additional analyses in which other parameters, such as back pain, non-vertebral fractures, additional fracture risk for more than two previous vertebral fractures, and the decline in teriparatide efficacy, were included. Extensive results of the sensitivity analyses were also reported. These showed that the cost-effectiveness was sensitive to the relative risk of fracture and the efficacy of teriparatide. The cost-effectiveness acceptability curve showed that if a decision-maker was willing to pay EUR 50,000 per QALY gained, the probability that teriparatide was cost-effective in the recent fracture group would be about 90%.
Authors' conclusions The study results indicated that teriparatide treatment might be cost-effective in comparison with no treatment in high-risk populations, for example, those with a recent fracture and a bone mineral density (BMD) T-score of less than or equal to -3.0. Also, the study indicated that the cost-effectiveness of treatments for osteoporosis is highly dependent on the timing of treatment initiation relative to the fracture.
CRD COMMENTARY - Selection of comparators The comparator was calcium and vitamin D alone. The authors acknowledged the existence of other treatments for osteoporosis but said that there were no clinical trials comparing them with teriparatide that had fracture as a primary end point. You should decide if the comparator represents current practice in your own setting. Validity of estimate of measure of effectiveness The authors combined data from existing models with data from several published studies of varying designs. No systematic search for data was reported, which means we cannot be sure that the best available evidence was used. The parameters for the model were derived from published studies, mainly a randomised double-blind placebo-controlled fracture prevention trial (Neer et al. 2001) and a population-based study (Kanis et al. 2000).
Validity of estimate of measure of benefit The estimation of health benefits (QALYs) was modelled using a Markov model. The methods used to estimate the utility weights were not described as they were taken from a published paper (Lundberg 1999).
Validity of estimate of costs The authors adopted a societal perspective. No productivity costs were evaluated, but this may be considered reasonable as the population was of retirement age. It was unclear whether patient expenditure on home adjustments was either relevant or considered. Relevant cost categories, as well as their costs, were taken into consideration. The resource use quantities and the unit costs were not reported separately, which would make it difficult to rework the analysis for other settings. The price year and the sources of the resource use data and unit costs were adequately reported. The costs were discounted at an annual rate of 3%, which seems appropriate in this instance. Sensitivity analyses of the costs were conducted to assess the robustness of the estimates used.
Other issues The authors compared their findings with those from other studies and found their results to be in agreement. The issue of the generalisability of the results to other settings was not addressed. The results of the study do not appear to have been presented selectively. The authors' conclusions would appear to be an adequate reflection of the scope of the analysis.
Implications of the study The findings have important implications for the treatment of osteoporotic patients in clinical practice, as the study provides further evidence of the clinical and economic benefit of starting treatments for osteoporosis early after previous fractures as well as the early identification of these patient groups.
Source of funding Supported by Lilly Europe.
Bibliographic details Lundkvist J, Johnell O, Cooper C, Sykes D. Economic evaluation of parathyroid hormone (PTH) in the treatment of osteoporosis in postmenopausal women. Osteoporosis International 2006; 17(2): 201-211 Other publications of related interest Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information.
Jonsson B, Christiansen C, Johnell O, Hedbrandt J. Cost-effectiveness of fracture prevention in established osteoporosis. Osteoporos Int 1995;5:136-42.
Zethraeus N, Jonsson B, Lindgren P. A computer model to analyze the cost-effectiveness of hormone replacement therapy - a revised version. Stockholm: Economic Research Institute; 2000.
Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, et al. Effect of parathyroid hormone (I-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001;344:1434-41.
Kanis JA, Johnell O, Oden A, Sernbo I, Redlund-Johnell I, Dawson A, et al. Long term risk of osteoporotic fracture in Malmo. Osteoporos Int 2000;11:669-74.
Johnell O, Kanis JA, Oden A, Sernbo I, Redlund-Johnell I, Petterson C, et al. Fracture risk following an osteoporotic fracture. Osteoporos Int 2004;15:175-9.
Johnell O, Kanis JA, Oden A, Sernbo I, Redlund-Johnell I, Petterson C, et al. Mortality after osteoporotic fractures. Osteoporos Int 2004;15:38-42.
Lundberg L. Health-related quality of life in Sweden (dissertation). Uppsala: Uppsala University, Faculty of Pharmacy; 1999.
Zethraeus N. Costs and quality of life associated with osteoporosis related fractures - based on a Swedish pilot study. Stockholm: Stockholm School of Economics, Centre for Health Economics; 2002.
Indexing Status Subject indexing assigned by NLM MeSH Aged; Bone Density /physiology; Bone Density Conservation Agents /economics /therapeutic use; Cost of Illness; Cost-Benefit Analysis /methods; Female; Fractures, Bone /economics /prevention & Hip Fractures /economics /prevention & Humans; Models, Economic; Osteoporosis, Postmenopausal /drug therapy /economics /mortality; Quality-Adjusted Life Years; Risk Factors; Spinal Fractures /economics /prevention & Teriparatide /economics /therapeutic use; control; control; control AccessionNumber 22006006644 Date bibliographic record published 31/07/2007 Date abstract record published 31/07/2007 |
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