Prevention of osteoporosis: cost-effectiveness of different pharmaceutical treatments Ankjaer-Jensen A, Johnell O

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1 Prevention of osteoporosis: cost-effectiveness of different pharmaceutical treatments Ankjaer-Jensen A, Johnell O 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 pharmaceutical treatments programmes for osteoporosis were compared: calcium supplementation, etidronate, and calcitonin. In addition, the implementation of treatment following screening for low bone marrow density individuals was examined. Type of intervention Primary prevention; Screening. Economic study type Cost-effectiveness analysis. Study population A hypothetical cohort of women aged 50. Setting Community. The economic analysis was conducted in Copenhagen, Denmark. Dates to which data relate Effectiveness data were collected from studies published between 1980 and Resource use data were partly taken from a study conducted in The dates for the other resource use data were not stated. The price year used was not stated. Source of effectiveness data For the three pharmaceutical treatments, a review of studies was used. The same was true for the HRT therapy. In addition, several assumptions were made by the authors for the other strategy investigated (screening). Modelling A simulation model following a cohort of 1, year-old women was used to calculate outcomes, treatment costs and cost of side effects. Outcomes were based on variations in the number of bone fractures with and without treatment, varying the efficacy of treatment, varying the age of the cohort and the risk of side effects. Outcomes assessed in the review The outcomes assessed were the reduced risk of bone fractures using the selected pharmaceutical treatments and also using Hormone Replacement Therapy (HRT). In addition an assessment was made of the risk of cardiovascular disease and breast cancer following the use of HRT. Page: 1 / 6

2 Study designs and other criteria for inclusion in the review The designs of the studies included for determining the effectiveness of the pharmaceutical treatments were not clearly stated. Sources searched to identify primary studies Not stated. Criteria used to ensure the validity of primary studies Not stated. Methods used to judge relevance and validity, and for extracting data The methods used to judge the relevance and validity of primary studies were not stated. The method for extracting data from individual studies was not stated. Number of primary studies included Seven studies were included in the review. These studies included two meta-analyses, the first of which was a 1995 analysis which reviewed therapies to prevent fractures in the elderly whilst the other, 1992 analysis, examined the impact of HRT on the risk of fractures. The risk of fracture following etidronate therapy was taken from a 1990 study, which conducted a follow-up on a group of patients three years after therapy. The types of the other four studies were not clearly stated. Methods of combining primary studies Primary studies were not combined to determine the relative risk of a fracture following calcitonin and HRT therapy (best-worst case scenario analyses were used in the simulations that followed). The relative risks following etidronate and calcium were each based only on single studies. Investigation of differences between primary studies Not stated. Results of the review The authors estimated the relative risk of a fracture in both an optimistic and pessimistic scenario. In the pessimistic scenario the protective effects of therapy decreased linearly after the first five years for the pharmaceutical therapy. For calcitonin, the authors estimated a relative risk of fracture to be 0.23 for the lifetime of a woman, in the optimistic scenario, and 0.70 over the first five years with a linear decrease in effect thereafter, in the pessimistic scenario. Similarly for etidronate and calcium relative risk was 0.5 in both the optimistic and pessimistic scenarios. The relative risk of a fracture following HRT in the optimistic scenario for 30 years was 0.50, whilst in the pessimistic scenario this was 0.75 for the first 10 years and 0.85 for the next five years. The risk of cardiovascular disease when using HRT was estimated to be 0.50 until 30 years after treatment, in the optimistic scenario, and 0.65 for 10 years after treatment and 0.75 for years in the pessimistic scenario. The risk of breast cancer after using HRT in the optimistic scenario was 0 for the first 10 years, 1.30 for the years 10-20, and 0 after 20 years. In the pessimistic scenario, there was assumed to be a linear increase in the risk of breast cancer in the first 10 years, with a relative risk of 1.30 for the next 10 years, and no increase in relative risk after this period of time. Methods used to derive estimates of effectiveness Current recommendations were used to determine the length of therapy and the authors also made assumptions about the length of the protective effect following the discontinuation of therapy. Page: 2 / 6

3 Estimates of effectiveness and key assumptions The duration of pharmaceutical treatment was assumed to be five years and two assumptions were adopted concerning the length of the protective effect of therapy. In the optimistic scenario, the authors assumed that there would be a constant effect for the lifetime of a woman whilst in the pessimistic scenario the authors assumed that the protective effects decreased linearly with no protective effect after 25 years. Additionally, the authors also assumed the same reduction of risk of fracture for the hip, forearm and vertebrae. A reduction in the risk of cardiovascular disease was assumed to decrease the number of bed days and hospital admissions by the same rate. Measure of benefits used in the economic analysis The measure of benefits used in the economic analysis were hip, forearm and vertebrae fractures avoided. These benefits were estimated using a model. Reviewer's note: Only the former benefits (in terms of hip fractures avoided) were abstracted here because to space constraints. Direct costs These costs included nursing and physician time, diagnostic and therapeutic services and the 'hotel' costs of care. The direct programme costs for calcitonin, etidronate, calcium, HRT (pills and plaster) were estimated. Costs were discounted at a rate of 5%. The direct costs associated with hip fractures, fractures of the forearm, vertebral fracture, cardiovascular disease, breast cancer and screening programmes were also estimated. Quantities of resource use were analysed separately from the costs. The cost associated with hip fractures were taken from a 1994 Danish study. The total costs associated with each strategy were estimated using a model. The price year was not clearly stated. Indirect Costs The authors decided not to include these costs as many of the women in the analyses were over retirement age. Currency Danish kroner (DKr) Sensitivity analysis A best-worst case scenario analysis ("pessimistic" and "optimistic" scenarios) was performed. These scenarios varied the estimates of efficacy of the pharmaceutical treatments or HRT. The sensitivity of the cost-effectiveness ratios to the costs of vertebral fractures, hip replacements and other programme costs were investigated. Other parameters varied were the use of discounting, age at which treatment commences, compliance rates and varying the costs of the screening programme. Estimated benefits used in the economic analysis With the no-screening programmes, assuming that the age at onset of treatment was 70 years in all women and 100% compliance, the average number of hip fractures avoided was estimated, using calcitonin, to be 0.17 in the optimistic scenario and 0.04 in the pessimistic scenarios. Similarly, the number of hip fractures avoided were 0.11 and 0.07 for etidronate, 0.11 and 0.03 for calcium supplements, and 0.11 and 0.08 with HRT for the optimistic and pessimistic scenarios, respectively. Using screening with BMD (assuming 70 years of age at screening and treatment onset) the average number of hip fractures per individual for each treatment under the pessimistic scenario were as follows: calcitonin 0.02 and 0.01 (100% and 50% compliance rates respectively), etidronate 0.04 and 0.02, and calcium 0.02 and The additional number of hip fractures avoided using the universal ("population based") approach rather than the screening based approach at 100% compliance, under the pessimistic scenario was 0.02 using calcitonin, 0.03 using etidronate, and 0.01 using calcium supplements. Similarly, with 50% compliance rates, the corresponding numbers of additional hip fractures avoided were 0.03, 0.05 and 0.02, respectively. The duration of benefits was assumed under the optimistic scenario to be for the lifetime of the patient and for the pessimistic scenario to be for 25 years. Side effects of HRT, reduced risk of cardiovascular disease and increased risk of breast cancer were considered in the economic analysis. Page: 3 / 6

4 Cost results The average total programme costs per patient for calcitonin, assuming that all women were 70 years of age at treatment onset, were DKr24,191 and DKr34,678 in the optimistic and pessimistic scenarios, respectively. Similarly the programme costs for etidronate were DKr1,195 and DKr1,709 for the optimistic and pessimistic scenarios, respectively. For calcium supplement therapy the total costs of the programme were DKr837 and DKr6,849 in the optimistic and pessimistic scenarios. The programme costs for the HRT pill programme were DKr-4,280 and DKr5,343 for the optimistic and pessimistic scenarios. The cost of HRT plaster programme were DKr662 and DKr9,285 for the optimistic and pessimistic scenarios, respectively. As for the screening programmes, using the pessimistic assumptions, calcitonin had costs of DKr8,354 and DKr4,644 (100% compliance and 50% compliance, respectively). The corresponding incremental costs incurred by the no-screening option were DKr26,324 and DKr30,034. Similarly for etidronate the costs were DKr-618 and DKr160, and DKr2,327 and DKr1,549 incremental costs for the corresponding no-screening option. For calcium, costs were DKr1,626 and DKr1,283, respectively, under 100% and 50% compliance, and DKr5,223 and DKr5,566 incremental costs without screening were estimated. Synthesis of costs and benefits For the no screening option, the average costs of the calcitonin strategy per hip fracture avoided relative to no intervention, varied between DKr142,300 and DKr866,950 (best and worst cases). For etidronate, the corresponding figures were DKr-10,864 and DKr24,414, and for calcium supplements these were DKr7,609 and DKr228,300, respectively. For 'HRT pill' the cost-effectiveness varied between DKr-38,909 to DKr178,100, and for 'HRT plaster' the cost effectiveness varied between DKr6,018 and DKr309,500. The average cost effectiveness per hip fracture avoided (worst case scenario with the no-intervention alternative) using the screening method was for calcitonin DKr417,700 and DKr464,400 for 100% and 50% compliance rates. The corresponding figures for etidronate were DKr-15,450 (100%) and DKr8,000 (50%) and for calcium DKr81,300 (100%) and DKr128,300 (50%). The estimates of incremental cost per additional hip fracture avoided for the no-screening options relative to the screening ones were derived at both the 100% and 50% compliance rates using the worst case scenarios. For calcitonin, the figures were DKr1,136,200 and DKr1,001,133, respectively, for the 100% and 50% compliance rates. For etidronate, the corresponding figures were DKr77,567 and DKr 30,980, respectively. As for calcium supplements, those figures were DKr522,300 and DKr278,300, respectively. For the no-screening option, a decrease in the cost of treating hip fractures by 50%, when using pessimistic assumptions, worsened the incremental estimate of calcium supplementation from DKr228,000 per hip fracture avoided to DKr283,000 per hip fracture avoided. A 50% reduction in the price of pharmaceuticals improved cost effectiveness in the pessimistic scenario from DKr866,950 to DKr353,634 per hip fracture avoided for calcitonin, and similarly for etidronate from DKr24,414 to DKr-36,357, and for calcium from DKr228,300 to DKr49,422. The cost-effectiveness of treatments increased when the treatment was delayed to age 80 rather than age 70 with the average cost effectiveness per hip fracture avoided of calcitonin, etidronate and calcium falling to DKr555,000, DKr-34,000 and DKr85,000, respectively. When the cost of screening was increased by 100% (from DKr1,000 to DKr2,000) the cost-effectiveness of etidronate relative to no-intervention decreased from DKr-15,450 to DKr8,518. (100% compliance, pessimistic assumptions). Authors' conclusions The authors concluded that there is a wide degree of variation in the cost-effectiveness of different pharmaceutical treatments to prevent osteoporosis. Whilst screening using bone measurement density is more cost-effective, even at 50% compliance rates, than no screening, the authors concluded that screening prevention programmes should not be implemented until further research is done to determine that compliance of individuals to therapy. Other studies have shown the compliance with treatment protocols may be very low and that in fact many women identified as being at risk from osteoporosis may decline treatment. In addition, the measure of benefit (hip fractures avoided) does not allow for the comparison of pharmaceutical therapy with HRT due to the additional effects of HRT. CRD COMMENTARY - Selection of comparators No justification was given for the comparators used in the economic evaluation. You should consider whether these are appropriate comparators in your own setting. HRT therapy was also included in the analysis of the population based approach but, as pointed out by the authors, the comparison of the pharmaceutical strategies with HRT is difficult due Page: 4 / 6

5 to the additional effects of the latter option in terms of risk of CVD and breast cancer. Validity of estimate of measure of benefit Not enough information was provided by the authors as to the methods they have used to identify the studies used to estimate measures of benefit, although they have conducted an analysis of extremes to account for the wide variation in potential effectiveness and duration of effect of the different comparators. Validity of estimate of costs In general adequate details were provided, although more information would have helped to determine how the programme costs were derived. In particular, no information was given on the price year used. Other issues As pointed out by the authors, the cost data are appropriate to Denmark only and cannot be applied to other countries without suitable adjustments. The results of sensitivity analyses were presented in a selective manner and it may have been helpful to have more information on the results of those analyses. A presentation of results in the form of an incremental analysis would have been illustrative for comparison of the different drug strategies (i.e. etidronate versus calcitonin, calcium versus etidronate, etc.). Implications of the study As the authors noted, methods for measuring quality of life using HRT and other therapies for the management of osteoporosis should be developed, along with additional studies examining compliance and alternative therapeutic strategies. The authors also felt that programmes to change lifestyle, such as increased exercise, decreased smoking and dietary changes to increase calcium or vitamin D should also be incorporated into future economic evaluations. Source of funding None stated. Bibliographic details Ankjaer-Jensen A, Johnell O. Prevention of osteoporosis: cost-effectiveness of different pharmaceutical treatments. Osteoporosis International 1996; 6(4): PubMedID Indexing Status Subject indexing assigned by NLM MeSH Aged; Bone Density; Computer Simulation; Cost-Benefit Analysis; Female; Health Care Costs; Humans; Mass Screening /economics /methods; Middle Aged; Models, Theoretical; Osteoporosis, Postmenopausal /complications /prevention & control AccessionNumber Date bibliographic record published 31/01/1999 Date abstract record published Page: 5 / 6

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