O. Ström

Cost-effectiveness of the treatment and prevention of osteoporosis : a review of the literature and a reference model

ObjectiveThe purpose of the paper is to update and review the latest developments related to modelling and economic evaluation of osteoporosis in the period 2002–2005 and further to present a reference model for the assessment of the cost-effectiveness of the prevention and treatment of osteoporosis.DiscussionThe reference model is intended to be used for fracture specific interventions affecting the risk of fracture. An interface version and an extensive description of the model is available on the internet (http://www.healtheconomics.se) and also accessible via the International Osteoporosis Foundation (http://www.osteofound.org). The purpose of the reference model is to improve the quality and comparability of cost-effectiveness analysis in the osteoporosis field and to serve as a tool for validation of present and future cost-effectiveness models. The reference model allows the cost-effectiveness analysis to be carried out from a societal perspective including intervention, morbidity and mortality costs. The model has been extensively tested and calibrated, and meets the properties of good decision analytic modelling. The model is a state transition Markov cohort model, which is characterised by a 50-year time horizon divided into one year cycle lengths. The following health states are included: “healthy”, “hip fracture”, “spine fracture”, “wrist fracture”, “other fracture”, and “dead”.ConclusionThe model is flexible and allows for the estimation of the cost-effectiveness over different ranges for a selected number of variables (e.g., age, fracture risk, cost of intervention).

FRAX® and its applications in health economics—Cost-effectiveness and intervention thresholds using bazedoxifene in a Swedish setting as an example

BACKGROUND An important aspect of cost-effectiveness analysis of osteoporosis is to accurately model the fracture risk and mortality related to the patient groups in the analysis. The estimation of fracture risk is based on a number of factors, such as the level of general risk of the normal population, the effect of treatment and the prevalence of clinical risk factors (CRFs) for fracture. Fracture risk has traditionally been calculated with risk adjustments based on age, bone mineral density and prior vertebral fracture. The treatment effect has been derived from clinical trials and, in the absence of subgroup analyses, the same efficacy has been assumed irrespective of the fracture risk of the population. The FRAX tool enables the estimation of risk based on a wider range of risk factors, and treatment efficacy that is dependent on the level of risk in the analyzed population. The objective was to describe the implementation of the FRAX algorithms into health economic osteoporosis models and to highlight how it differs from traditional risk assessment. METHODS The selective estrogen receptor modulator, bazedoxifene, was evaluated in a Swedish setting with traditional and FRAX-based risk assessment in a previously developed Markov model that included fractures and thromboembolic events, and also was adapted to accommodate risk-dependent efficacy, which is available for bazedoxifene. RESULTS The traditional approach gave lower ICERs at ages up to 60 years compared to the FRAX method when only considering age, BMD and prior fracture. At 70 years and older and when adding more CRFs with the FRAX approach, the FRAX ICER decreased and fell below the traditional approach. The risk dependant efficacy was the main reason for lower ICERs with FRAX in women at higher risk of fracture. DISCUSSION FRAX applied in cost-effectiveness analyses is a more granular method for the estimation of fracture risk, mortality and efficacy compared to previous approaches that can also improve case finding. Furthermore, it facilitates the estimation of cost-effectiveness for various types of patients with different combinations of CRFs, which more closely matches patients in clinical practice.

The societal burden of poor persistence to treatment of osteoporosis in Sweden

OBJECTIVES Poor persistence to prescribed treatment regimens is a well-documented health problem. The issue is of particular importance in treatment of chronic diseases, such as osteoporosis. The objective of this study was to estimate the annual societal burden of real-world persistence to treatment of osteoporosis in Sweden. A second aim was to estimate the monetary net benefit of improved persistence. METHODS The annual societal burden was evaluated in relation to perfect persistence to a five-year treatment duration and performed using a published Markov model by Ström and colleagues. The target population was extracted from the Swedish Prescribed Drug Register and based on all treatment-naïve patients who started therapy of primary osteoporosis in Sweden during 2009. Five hypothetical interventions were investigated, with improvements in the persistent proportion of between 10% and 50%. RESULTS Annually, a total of 1018 fractures were estimated to be caused by non-persistence to treatment of osteoporosis in Sweden. These fractures resulted in a substantial waste of health care resources related to morbidity (€26 million annually) and a loss, in total, of 771 quality-adjusted life-years (QALYs). Using a societal willingness-to-pay for a QALY of €60000, the total annual societal burden, incorporating both monetary consequences and health effects, was estimated at €62.76 million. Given current Swedish cost-effectiveness guidelines, between approximately €225 and €1130 could be spent per patient to increase persistence, depending on the level of improvement (between 10% and 50%). CONCLUSIONS The total annual societal burden of current, real-world persistence was estimated at €63 million. The estimated additional fracture-related costs associated with poor persistence were larger than the current total annual expenditure on all osteoporosis medications in Sweden. Poor persistence to treatment of osteoporosis should consequently be acknowledged as an important and costly health problem, and be taken into account when evaluating osteoporosis interventions.

Identifying cost-effective treatment with raloxifene in postmenopausal women using risk algorithms for fractures and invasive breast cancer

INTRODUCTION The National Osteoporosis Foundation (NOF) recommends considering treatment in women with a 20% or higher 10-year probability of a major fracture. However, raloxifene reduces both the risk of vertebral fractures and invasive breast cancer so that raloxifene treatment may be clinically appropriate and cost-effective in women who do not meet a 20% threshold risk. The aim of this study was to identify cost-effective scenarios of raloxifene treatment compared to no treatment in younger postmenopausal women at increased risk of invasive breast cancer and fracture risks below 20%. METHOD A micro-simulation model populated with data specific to American Caucasian women was used to quantify the costs and benefits of 5-year raloxifene treatment. The population evaluated was selected based on 10-year major fracture probability as estimated with FRAX® being below 20% and 5-year invasive breast cancer risk as estimated with the Gail risk model ranging from 1% to 5%. RESULTS The cost per QALY gained ranged from US

Costs Related to Hip Disease in Patients Eligible for Total Hip Arthroplasty

22,000 in women age 55 with 5% invasive breast cancer risk and 15-19.9% fracture probability, to

Patient preferences for characteristics differentiating ovarian stimulation treatments

110,000 in women age 55 with 1% invasive breast cancer risk and 5-9.9% fracture probability. Raloxifene was progressively cost-effective with increasing fracture risk and invasive breast cancer risk for a given age cohort. At lower fracture risk in combination with lower invasive breast cancer risk or when no preventive raloxifene effect on invasive breast cancer was assumed, the cost-effectiveness of raloxifene worsened markedly and was not cost-effective given a willingness-to-pay of US

The comparative gastrointestinal tolerability of proprietary versus generic alendronate in patients treated for primary osteoporosis

50,000. At fracture risk of 15-19.9% raloxifene was cost-effective also in women at lower invasive breast cancer risk. CONCLUSIONS Raloxifene is potentially cost-effective in cohorts of young postmenopausal women, who do not meet the suggested NOF 10-year fracture risk threshold. The cost-effectiveness is contingent on their 5-year invasive breast cancer risk. The result highlights the importance of considering a womans full risk profile when considering anti-osteoporosis treatment.

Osteoporosis: burden, health care provision and opportunities in the EU A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA)

This study was designed to estimate direct and indirect costs incurred by hip disease in patients eligible for total hip arthroplasty (THA). Before THA, 2635 patients completed a questionnaire regarding the use of resources because of their hip disease. Costs were assigned using official statistical sources or market prices. Annual costs amounted to US

Adherence to treatment of primary osteoporosis and its association to fractures—the Swedish Adherence Register Analysis (SARA)

7666 per patient. In a regression analysis, higher annual costs were associated with working age, female gender, comorbidity, and operation waiting time more than 90 days (P < .005). The burden of disease for THA candidates is extensive, where loss of productivity is the principal cost. Long wait for surgery is associated with increased costs. This study provides baseline cost data, which will be useful for further health economic analyses and could provide guidance for health care decision makers.

Cost-effectiveness of Denosumab for the treatment of postmenopausal osteoporosis

BACKGROUND Little is known concerning patient preferences for IVF treatments. The objective of this study was to elicit patient preferences for characteristics differentiating ovarian stimulation treatments. METHODS Women undergoing IVF were recruited from six clinics in Sweden between May 2010 and December 2010. Included patients completed a study questionnaire consisting of one contingent valuation (CV) question (with six different bids) and 16 conjoint analysis (CA) questions formulated as discrete choices between two hypothetical ovarian stimulation treatments (defined in terms of manufacturing method, method of administration, time required for administration, dose variability and hypothetical price). Patient preferences were derived using multinomial logit modelling. RESULTS The final study population consisted of 294 women (mean age of 35). Respondents were willing to pay €360 [95% confidence interval (CI): €340-€390] to receive FSH derived from DNA technology instead of highly purified extract from urine from post-menopausal women, €300 (95% CI: €280-€320) to administer the FSH using a prefilled injection pen instead of a conventional syringe, €30 (95% CI: €20-€40) per saved minute required for administration and €530 (95% CI: €500-€570) to reduce the dose variability from 10-20% to 1-2% (P< 0.001 for all estimates). The result from the CV was similar to the CA. CONCLUSIONS Women undergoing IVF place significant value on characteristics differentiating ovarian stimulation treatments. Product-specific aspects should be taken into account by decision-makers when discriminating between commercial gonadotrophins in clinical practice to align health-care decision-making with patient preferences and potentially improve the effectiveness of IVF interventions through enhanced patient satisfaction and treatment compliance. Preferences for treatment characteristics should also be considered in evaluations of ovarian stimulation products to capture their true value from a patient perspective.