Is it time to consider population screening for fracture risk in postmenopausal women? A position paper from the International Osteoporosis Foundation Epidemiology/Quality of Life Working Group.

The IOF Epidemiology and Quality of Life Working Group has reviewed the potential role of population screening for high hip fracture risk against well-established criteria. The report concludes that such an approach should strongly be considered in many health care systems to reduce the burden of hip fractures. INTRODUCTION: The burden of long-term osteoporosis management falls on primary care in most healthcare systems. However, a wide and stable treatment gap exists in many such settings; most of which appears to be secondary to a lack of awareness of fracture risk. Screening is a public health measure for the purpose of identifying individuals who are likely to benefit from further investigations and/or treatment to reduce the risk of a disease or its complications. The purpose of this report was to review the evidence for a potential screening programme to identify postmenopausal women at increased risk of hip fracture. METHODS: The approach took well-established criteria for the development of a screening program, adapted by the UK National Screening Committee, and sought the opinion of 20 members of the International Osteoporosis Foundation's Working Group on Epidemiology and Quality of Life as to whether each criterion was met (yes, partial or no). For each criterion, the evidence base was then reviewed and summarized. RESULTS AND CONCLUSION: The report concludes that evidence supports the proposal that screening for high fracture risk in primary care should strongly be considered for incorporation into many health care systems to reduce the burden of fractures, particularly hip fractures. The key remaining hurdles to overcome are engagement with primary care healthcare professionals, and the implementation of systems that facilitate and maintain the screening program.

Long-term cost-effectiveness of screening for fracture risk in a UK primary care setting: the SCOOP study.

Community-based screening and treatment of women aged 70-85 years at high fracture risk reduced fractures; moreover, the screening programme was cost-saving. The results support a case for a screening programme of fracture risk in older women in the UK. INTRODUCTION: The SCOOP (screening for prevention of fractures in older women) randomized controlled trial investigated whether community-based screening could reduce fractures in women aged 70-85 years. The objective of this study was to estimate the long-term cost-effectiveness of screening for fracture risk in a UK primary care setting compared with usual management, based on the SCOOP study. METHODS: A health economic Markov model was used to predict the life-time consequences in terms of costs and quality of life of the screening programme compared with the control arm. The model was populated with costs related to drugs, administration and screening intervention derived from the SCOOP study. Fracture risk reduction in the screening arm compared with the usual management arm was derived from SCOOP. Modelled fracture risk corresponded to the risk observed in SCOOP. RESULTS: Screening of 1000 patients saved 9 hip fractures and 20 non-hip fractures over the remaining lifetime (mean 14 years) compared with usual management. In total, the screening arm saved costs (£286) and gained 0.015 QALYs/patient in comparison with usual management arm. CONCLUSIONS: This analysis suggests that a screening programme of fracture risk in older women in the UK would gain quality of life and life years, and reduce fracture costs to more than offset the cost of running the programme.

The impact of different health dimensions on overall quality of life related to kyphoplasty and non-surgical management.

UNLABELLED: This study uses data from a previously published randomised trial where balloon kyphoplasty was compared to non-surgical management. Of the improved overall quality of life, 60 % was caused by decreased pain. However, ignoring other dimensions of quality of life would underestimate the procedure's effect. INTRODUCTION: Acute back pain has been viewed as the most important factor lowering quality of life (QoL) for patients suffering vertebral fractures. The objective of this study was to quantify the impact of different health dimensions on overall QoL using patient-reported outcome measurements (PROMs) collected in Fracture Reduction Evaluation (FREE) trial. METHODS: The analysis was based on patients included in the 2-year-long randomised controlled FREE trial studying the efficacy and safety of balloon kyphoplasty procedure (BKP) compared to non-surgical management (NSM). The PROMs included were EQ-5D, Short Form (SF)-36, visual analogue scale (VAS) pain and the Roland-Morris Disability Questionnaire (RMDQ). The health dimensional contribution to the overall QoL improvements was analysed by isolating the impact of each dimension on QoL in the SF-36 and EQ-5D, respectively. A correlation analysis of the QoL improvement was performed to investigate the relationships between the four instruments. RESULTS: Changes in pain explained 60 % of the quality-adjusted life years (QALY) gained in BKP vs. NSM followed by self-care (17 %), mobility (16 %) and usual activities (10 %) (EQ-5D). Health dimensions capturing the mental state had little impact on the QALY gained. The SF-36 dimensional analysis showed similar results. The correlation analysis showed that the correlation between VAS pain, RMDQ and QALY improvement was fairly weak. CONCLUSIONS: Changes in the pain dimension of health are the most important drivers for changes of overall QoL in patients treated with BKP or NSM. However, ignoring the impact of other dimensions would lead to an underestimation of the actual improvement in overall QoL.

Cost-effectiveness of bazedoxifene incorporating the FRAX® algorithm in a European perspective.

UNLABELLED: The cost-effectiveness of bazedoxifene was compared to placebo in France, Germany, Italy, Spain, Sweden and the UK from a healthcare perspective using FRAX® for both fracture risks and for treatment efficacy. Cost/QALY differences were explained to a large extent by differences in fracture risk. INTRODUCTION: In cost-effectiveness modelling of osteoporosis treatments, the fracture risk has traditionally been calculated with risk adjustments based on age, bone mineral density and prior fracture. However, knowledge of additional clinical risk factors contributes to fracture risk assessment as demonstrated by the FRAX® tool. Bazedoxifene, a new selective estrogen receptor modulator for the treatment and prevention of osteoporosis, has been shown in a phase III clinical trial to reduce the risk of osteoporotic fractures in women. In an analysis using FRAX®, the efficacy of bazedoxifene was greater in patients with higher fracture risk. METHODS: The aim of this study was to evaluate the cost-effectiveness of bazedoxifene compared to placebo in France, Germany, Italy, Spain, Sweden and the UK from a healthcare perspective using FRAX®. A Markov cohort model was adapted to incorporate the FRAX® risk factors. FRAX® produces relative risks for hip fractures and major osteoporotic fractures. Patients were given a 5-year intervention, reducing the risk of fractures in a risk-dependent manner. The effect of treatment on fractures was assumed to decline linearly over 5 years after the intervention. RESULTS: There are large cost/quality-adjusted life year variations between countries in the European setting studied. The base case values ranged from cost saving (Sweden) to EUR 105,450 (Spain) in 70-year-old women with a T-score of -2.5 SD and a prior fracture. CONCLUSION: Bazedoxifene can be a cost-effective treatment for postmenopausal osteoporosis. The variability between countries was explained to a large extent by differences in fracture risk, and the estimated cost-effectiveness was highly dependent on the population's FRAX®-estimated probability of major osteoporotic fracture.

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 $22,000 in women age 55 with 5% invasive breast cancer risk and 15-19.9% fracture probability, to $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 $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 woman's full risk profile when considering anti-osteoporosis treatment.

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.

Cost-effectiveness of raloxifene in the UK: an economic evaluation based on the MORE study.

Raloxifene treatment has been shown to reduce the risk of vertebral fractures and breast cancer in postmenopausal women. The long-term economic implications of treatment with raloxifene have not yet been investigated. The aim of this study was to assess the cost-effectiveness of treating postmenopausal women in the UK with raloxifene. A previously developed computer simulation model was used to estimate the cost-effectiveness of osteoporotic treatments with extra skeletal benefits. The model was populated with epidemiological data and cost data relevant for a UK female population. Data on the effect of treatment were taken from the Multiple Outcomes of Raloxifene (MORE) study, which recruited women with low bone mineral density or with a prior vertebral fracture. Cost-effectiveness was estimated using Quality Adjusted Life Years (QALYs) and life years gained as primary outcome measures. The cost per QALY gained of treating postmenopausal women without prior vertebral fractures was 18,000 pounds, 23,000 pounds , 18,000 pounds and 21,000 pounds at 50, 60, 70 and 80 years of age. Corresponding estimates for women with prior vertebral fractures were 10,000 pounds, 24,000 pounds, 18,000 pounds and 20,000 pounds. In relation to threshold values that are recommended in the UK, the analysis suggests that raloxifene is cost-effective in the treatment of postmenopausal women at an increased risk of vertebral fractures.