|Cost effectiveness of ibandronate for the prevention of fractures in inflammatory bowel disease-related osteoporosis: cost-utility analysis using a Markov model
|Kreck S, Klaus J, Leidl R, von Tirpitz C, Konnopka A, Matschinger H, Konig H H
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.
The study assessed the cost-effectiveness of bisphosphonate ibandronate combined with calcium/colecalciferon, compared with sodium fluoride plus calcium/colecalciferon and calcium/colecalciferon alone, to prevent osteopoenic or osteoporotic fracture risk in patients with inflammatory bowel disease in Germany, investigating patients of different age groups and with different severity levels of osteoporosis. The most cost-effective treatment was calcium monotherapy, while ibandronate plus calcium/colecalciferon was not economically attractive. The quality of the study methodology was very high in terms of the sources used and the presentation of results.
Type of economic evaluation
The objective of the study was to assess the cost-effectiveness of bisphosphonate ibandronate combined with calcium/colecalciferon, compared with another combination strategy (sodium fluoride plus calcium/colecalciferon) and with a monotherapy (calcium/colecalciferon alone), to prevent osteopoenic or osteoporotic fracture risk in patients with inflammatory bowel disease (IBD) in the German setting. Patients of different age groups and with different severity levels of osteoporosis as a complication of IBD were considered. Specifically, three patient populations: osteopoenic patients (T-score about –2.0), osteoporotic patients (T-score of –3.0) and osteoporotic patients older than 65 years of age.
The three strategies under examination were bisphosphonate ibandronate combined with calcium/colecalciferon (ibandronate strategy), sodium fluoride plus calcium/colecalciferon (fluoride strategy) and calcium/colecalciferon alone (calcium strategy). The treatments were given for 5 years.
This economic evaluation was based on a Markov model that simulated patient risk of fractures (vertebral, hip and wrist) on the basis of data on bone mineral density (BMD) derived from a randomised controlled trial (RCT). The time horizon was 10 years. The authors stated that a societal perspective was adopted.
The clinical estimates were derived from a selection of known relevant studies. The aforementioned RCT was carried out by the Department of Medicine at the University of Ulm in Germany. The study involved 210 patients with Crohn’s disease and low BMD (87 received ibandronate, 91 fluoride and 32 calcium). The length of follow-up was 42 months. The RCT was used to estimate the BMD of patients receiving the different treatment options. Fracture risk for osteopoenic and osteoporotic patients was taken from studies conducted in several European countries (not Germany). Details of the study results were given, but not the study design. Other estimates such as treatment effectiveness came from published studies, details of which were not given. A number of simplifying assumptions was also made. For example, treatment effectiveness after 5 years was assumed to decline linearly to 0. Age- and gender-specific overall mortality rates came from official life tables published by the German Federal Statistical Office.
Monetary benefit and utility valuations:
Utility valuations were based on two sources: a Swedish study that used EQ-5D values in patients experiencing a fracture and a survey of patients with Crohn’s disease in Germany.
Measure of benefit:
The summary benefit measure was the quality-adjusted life-years (QALYs). These were estimated using the decision model. An annual discount rate of 5% was applied to the benefits.
The economic analysis included the costs of medications and monitoring, treatment of fractures, and indirect costs related to productivity losses as a consequence of a fracture. The costs of treating fractures covered transportation, outpatient and hospital care, inpatient and outpatient rehabilitation, nursing home care and nursing care at home. Resource use for medications was derived from data from the RCT, while fracture costs were based on an expert survey carried out during 2002 at Ulm University. The medication costs were obtained from the Red List, hospital costs from the German Diagnosis-Related Group system, and other costs came from official German prices such as those determined by the German social health insurance. Productivity losses were valued using average German wages. The price year was 2004. The long-term costs were discounted at an annual rate of 5%. The costs were expressed in euros (EUR).
Analysis of uncertainty:
Both a deterministic and a probabilistic sensitivity analysis were carried out. The one- and two-way analyses focused on relative risks, fracture costs, length of simulation, discount rate, offset time of effect and utility values. The Monte Carlo simulation assigned probabilistic distributions to model inputs and determined the probability that a treatment was cost-effective.
The calcium strategy dominated the fluoride strategy, which was simultaneously less effective (fewer QALYs) and more expensive.
In all scenarios, ibandronate was slightly more effective and more expensive than calcium. For example, in osteoporotic women, the gain in QALYs with ibandronate was 0.00098 (6.24223 versus 6.24320) for an additional cost of EUR 2,685 (EUR 2,252 versus EUR 4,937).
The incremental cost per QALY gained with ibandronate in comparison with calcium alone ranged from a lowest value of EUR 407,373 for an older female population with osteoporosis to EUR 6,516,345 for a younger female population with osteopoenia.
The deterministic sensitivity analysis did not substantially alter the base-case results, although the cost-utility ratios were sensitive to relative risks of fracture for ibandronate compared with calcium, utility valuations and length of simulation. In the Monte Carlo simulation, the probability of an incremental cost per QALY gained with ibandronate being below the threshold of EUR 50,000 was never greater than 20.2% (old osteoporotic women), but in most simulations ibandronate was dominated or associated with very high cost-effectiveness ratios.
The authors concluded that a strategy with ibandronate to prevent fracture risk in osteopoenic or osteoporotic patients was unlikely to represent a cost-effective option in the German setting. The strategy with calcium monotherapy gave the greatest value for money in this specific patient population.
The authors did not provide an explicit justification for their selection of the interventions under examination, although they did explain that recent data from an RCT were available and this might explain their choice. In general, the interventions compared appeared to be relevant for the disease under examination and in the authors’ context.
The clinical estimates were derived from multiple sources, although the bulk of the evidence was based on data from an RCT, the design and basic characteristics of which should ensure the validity of these specific clinical inputs. However, the authors pointed out the small sample size of the trial. The authors used both low BMD and BMD-independent predictors of fractures, which represents a very interesting approach. A very detailed list of the results of the published studies used to derive fracture risk was given, although the study design was often not stated. Some estimates were derived from a meta-analysis, which represents another good source of data. However, since the use of multiple source might introduce some uncertainty in the robustness of these estimates, the authors undertook a deep sensitivity analysis in order to overcome these potential limitations. The approach used to derive the benefit measure was clear and appropriate. The use of QALYs is a strong feature of the analysis.
The categories of costs included in the analysis appear to have been consistent with the authors' stated perspective. Detailed information on the unit costs and quantities of resources used was provided. Other details, such as the price year and sources of the main cost categories, were given. These enhance the possibility of replicating the analysis in other settings and time periods.
Analysis and results:
The results of the base-case analysis and sensitivity analyses were presented clearly. The results were presented in terms of sub-groups, which were relevant for the disease under examination. The synthesis of the costs and benefits, with exclusion of the dominated strategy, was appropriate. Ranges of values and probabilistic distributions were clear. The authors stated that caution will be required if applying these findings to the German setting, as some key clinical data were derived from other settings.
Overall, the study methodology was very good, with satisfactorily presentation of the methods and results. The extensive sensitivity analysis enhances the robustness of the analysis.
Supported by a grant from the German Federal Ministry of Education and Research.
Kreck S, Klaus J, Leidl R, von Tirpitz C, Konnopka A, Matschinger H, Konig H H. Cost effectiveness of ibandronate for the prevention of fractures in inflammatory bowel disease-related osteoporosis: cost-utility analysis using a Markov model. PharmacoEconomics 2008; 26(4): 311-328
Other publications of related interest
von Tirpitz C, Klaus J, Hoffman J, et al. Treatment of osteoporosis in Crohn’s disease: final data of multicenter 3.5-years study comparing sodium fluoride, ibandronate and substitution of calcium and vitamin D. Gastroenterology 2005;128 (4 Suppl 2):A588.
Zethraeus N, Ben Sedrine W, Caulin F, et al. Models for assessing the cost-effectiveness of the treatment and prevention of osteoporosis. Osteoporos Int 2002;13:841-57.
Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996;312:1254-9.
Subject indexing assigned by NLM
Adult; Aged; Bone Density /drug effects; Bone Density Conservation Agents /economics /therapeutic use; Calcium /economics /therapeutic use; Cholecalciferol /economics /therapeutic use; Cost-Benefit Analysis; Diphosphonates /economics /therapeutic use; Drug Therapy, Combination; Female; Fractures, Bone /prevention & Germany; Humans; Inflammatory Bowel Diseases /complications; Male; Markov Chains; Models, Economic; Osteoporosis /etiology /prevention & Quality-Adjusted Life Years; Sodium Fluoride /economics /therapeutic use; control; control
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Date abstract record published