Cost-effectiveness of osteoporosis treatments in postmenopausal women using FRAX™ thresholds for decision

doi:10.1016/j.jbspin.2012.01.001

Joint Bone Spine

Volume 80, Issue 1, January 2013, Pages 64-69

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Abstract

Purpose

FRAX™ is a fracture prediction algorithm to determine a patient's absolute fracture risk. There is a growing consensus that osteoporosis treatment should be based on individual 10-year fracture probability, as calculated in the FRAX™ algorithm, rather than on T-scores alone.

Objective

Our objective was to evaluate the cost-effectiveness of five years of branded alendronate therapy in postmenopausal French women with a known FRAX™ score.

Method

A Markov cohort state transition model using FRAX™ values and whenever possible population-specific data and probabilities. We estimated the incremental cost-effectiveness ratio (ICER) of alendronate versus no treatment in postmenopausal women with FRAX™ ranging from 10 to 3%.

Outcomes

Number of women to treat (NNT) for preventing hip fracture, costs, quality-adjusted life-years, incremental cost-effectiveness ratios.

Results

The incremental cost-effectiveness ratios (ICER) compared to no treatment at age 70 ranged from €104,183 to €413,473 per QALY when FRAX™ decreased from 10 to 3%. The NNTs for preventing one hip fracture ranged from 97 to 388 according to age (50–80 years) and FRAX™. Sensitivity analyses showed that the main determinants of cost-effectiveness were adherence to therapy and cost of treatment.

Conclusion

Using French costs of branded drug and current estimates of treatment efficacy, alendronate therapy for 70-year-old women with 10-year probability of hip fracture of 10% just meets the accepted cost-effectiveness threshold. Improving treatment adherence and/or decreasing treatment cost lowers the ICER. The model however underestimates the potential benefit by excluding other fractures.

Introduction

Osteoporosis has a growing impact on health care resource utilisation, particularly in industrialised countries. In the United States and the European Union, approximately 30% of postmenopausal women have osteoporosis, and it has been predicted that up to half of these women with osteoporosis will subsequently experience fragility fracture [1]. Direct expenditures for the prevention and the treatment of osteoporotic fractures are expected to substantially increase in the coming decade, due to the overall ageing of the population and to the dramatic increase of the number of frail elderly people at risk of falls and fractures [2]. Treatments for osteoporosis have increasingly been placed in a health economic context in order to justify resource allocation and inform the development of clinical guidelines.

In 2008, WHO introduced a fracture prediction algorithm (FRAX™) to estimate the individual risk of fracture [3]. The absolute risk of fracture associated with osteoporosis can be used to assess a cost-effectiveness threshold for different treatment strategies. Several studies have addressed the economic value of specific agents and suggested that osteoporosis treatment could be based on a 10-year fracture probability, rather than on T-scores, age and the number of risk factors [4], [5], [6]. From a United States perspective, a five-year course of osteoporosis treatment with a generic of bisphosphonate was cost-effective when the 10-year hip fracture probability reached approximately 3% [7]. In a UK setting, treatment with a generic of alendronate was cost-effective at all ages when the 10-year probability of a major fracture exceeded 7% [5], [8]. However, the transferability of previous results across jurisdictions is problematic because the cost-effectiveness of health technologies varies across countries, depending upon the incidence of the disease, availability of health resources, clinical practice patterns, reimbursement and relative prices [9].

Osteoporosis guidelines developed by the French National Health Authority (Haute Autorité de santé [HAS]) recommended treatment based on the identification of risk factors and a Bone Mineral Density (BMD) value below the threshold of osteoporosis. Treatment is also recommended for women with a prevalent vertebral or hip fragility fracture [10]. Cost-effectiveness has not been considered so far in these indications, and France has not been included in studies of international comparisons.

The aim of this study was to evaluate the cost-effectiveness ratio of treating French postmenopausal women presenting a risk of osteoporotic hip fracture based on the FRAX™ values.

Section snippets

Methods

The cost-effectiveness of treating with alendronate was compared to no treatment in a French setting by simulating costs and outcomes in a cohort of postmenopausal women, defined by age of treatment initiation and risk of hip fracture.

Results

The cost-effectiveness of alendronate in 70-year old women at the threshold of FRAX™ ranging from 10 to 3 is shown in Table 2. In 70-year old women, treatment was barely cost-effective at 104,000 Euro per QALY. The lowest cost-effectiveness ratio was for 60-year old women, at FRAX™ 10 with a figure of 96,403 Euros per QALY (Fig. 2). For younger and older women the ICER increased (Fig. 2). As expected, cost-effectiveness worsened (increased) at any age with decreasing FRAX™, due to the lower

Discussion

Our study shows that treating postmenopausal women with a 10-year hip fracture risk of 10% with branded alendronate is more efficient than interventions based on 7% or 3% thresholds, with a cost-effectiveness ratio of roughly € 100,000/QALY. However, our model indicates that improved adherence use of generic drugs may lower the ICER to generally accepted values. In France, no explicit threshold exits but the WHO value of 3–5 times the per capita GDP per QALY suggests that 100,000 € per QALY is

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

Acknowledgements

The authors are indebted to Karen Brigham for her editorial assistance.

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Worldwide Fracture Prediction
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Citation Excerpt :
In the case of FRAX, fixed, age-dependent, and hybrid models have been selected in the UK, the United States, Canada, New Zealand, and Lebanon, taking into account current evidence from trials (T-scores), translational (the UK), cost-effectiveness (the United States, New Zealand), or other considerations. Cost-effectiveness analyses have been explored in various countries, such as Greece (125), France (171), Portugal (172), Sweden (173), Switzerland (77), the UK (174,175), the United States (121), and Europe (176,177). The incorporation of risk assessment tool in guidelines is as dynamic as FRAX is.
The substantial increase in the burden of non-communicable diseases in general and osteoporosis in particular, necessitates the establishment of efficient and targeted diagnosis and treatment strategies. This chapter reviews and compares different tools for osteoporosis screening and diagnosis; it also provides an overview of different treatment guidelines adopted by countries worldwide. While access to dual-energy X-ray absorptiometry to measure bone mineral density (BMD) is limited in most areas in the world, the introduction of risk calculators that combine risk factors, with or without BMD, have resulted in a paradigm shift in osteoporosis screening and management. To-date, forty eight risk assessment tools that allow risk stratification of patients are available, however only few are externally validated and tested in a population-based setting. These include Osteoporosis Self-Assessment Tool; Osteoporosis Risk Assessment Instrument; Simple Calculated Osteoporosis Risk Estimation; Canadian Association of Radiologists and Osteoporosis Canada calculator; Fracture Risk Assessment Calculator (FRAX); Garvan; and QFracture. These tools vary in the number of risk factors incorporated. We present a detailed analysis of the development, characteristics, validation, performance, advantages and limitations of these tools. The World Health Organization proposes a dual-energy X-ray absorptiometry-BMD T-score ≤ -2.5 as an operational diagnostic threshold for osteoporosis, and many countries have also adopted this cut-off as an intervention threshold in their treatment guidelines. With the introduction of the new fracture assessment calculators, many countries chose to include fracture risk as one of the major criteria to initiate osteoporosis treatment. Of the 52 national guidelines identified in 36 countries, 30 included FRAX derived risk in their intervention threshold and 22 were non-FRAX based. No universal tool or guideline approach will address the needs of all countries worldwide. Osteoporosis screening and management guidelines are best tailored according to the needs and resources of individual counties. While few countries have succeeded in generating valuable epidemiological data on osteoporotic fractures, to validate their risk calculators and base their guidelines, many have yet to find the resources to assess variations and secular trends in fractures, the performance of various calculators, and ultimately adopt the most convenient care pathway algorithms.
Establishing and evaluating FRAX<sup>®</sup> probability thresholds in Taiwan
2017, Journal of the Formosan Medical Association
Citation Excerpt :
When applying the Markov model using Taiwanese data, our intervention threshold based on MOF was higher than that in Spain or Hong Kong,27,28 but lower than that in Japan,29 Switzerland,30 or the USA.10 Similarly, our intervention threshold for HF is lower than that in France but higher than the US threshold.10,31 There may be several reasons for these differences.
The Taiwanese FRAX^® calculator was launched in 2010. However, cost-effectiveness thresholds for the prescription of antiosteoporosis medications were not established. This study aims to establish and evaluate FRAX^®-based probability thresholds in Taiwan.
Using previous data from Taiwan and literature, we determined cost-effectiveness thresholds for prevention of osteoporotic fractures by alendronate with a Markov model, as well as using two other translational approaches. Sensitivity analysis was applied using different alendronate prices. A clinical sample was used to test these Taiwan-specific thresholds by determining the percentages of high-risk patients who would be qualified for current National Health Insurance reimbursement.
With the Markov model, the intervention threshold for hip fracture was 7% for women and 6% for men; for major osteoporotic fracture, it was 15% for women and 12.5% for men. Both translational approach models were cost effective only for certain age groups. However, if branded alendronate was reimbursed at 60% of the current price, they became cost effective in almost all age groups. This clinical screening study showed that the National Health Insurance Administration model identified the highest proportion (44%) of patients qualified for National Health Insurance reimbursements, followed by the Markov model (30%), and the United States model (22%).
Three FRAX^®-based models of alendronate use were established in Taiwan to help optimize treatment strategies. The government is encouraged to incorporate FRAX^®-based approaches into the reimbursement policy for antiosteoporosis medicines.
Managing osteoporosis with FRAX® in Australia: Proposed new treatment thresholds from the 45&Up Study cohort
2014, Bone
Citation Excerpt :
They should be identified and have the opportunity to become candidates for intervention. There is no universally accepted fracture risk level for osteoporosis pharmacologic therapy [7–10]. Intervention thresholds with FRAX vary from country to country due to not only different approaches used in setting the thresholds [11–13] but also differences in the risks of fracture and death between countries [14].
Many people at high risk of fractures are not following traditional guidelines and not being recommended for intervention. This study aimed to propose and evaluate a new set of intervention thresholds.
Participants were 213,375 men and women aged ≥ 50 years living in New South Wales, Australia. Fracture Risk Assessment Paper Charts (Australia) was used to estimate the 10-year fracture risk. The standardized rates (to Australia population distribution 2007) for intervention were calculated for different thresholds: our proposed new thresholds (i.e. 10-year probability of hip fracture: ≥ 3%, 5% or 7% for 50–69, 70–79 and ≥ 80 years respectively), thresholds by the National Osteoporosis Guideline Group (NOGG) approach, UK thresholds and US thresholds.
The NOGG, UK and US thresholds did not work well in the Australian population. For example, the NOGG and UK thresholds respectively qualified only 1 in 12 (8.1%) and 1 in 9 (11.3%) Australian men aged ≥ 70 years and the US thresholds qualified about 9 in 10 (90.6%) Australian women aged ≥ 70 years. For men or women aged ≥ 70 years, our proposed new thresholds gave more realistic treatment rates of 21.6% for men and 70.5% for women. Compared to the current Australian guidelines (i.e. T-score ≤ − 2.5 and age ≥ 70 years or a fragility fracture), our thresholds identified an additional 4.9% of men and 18.2% of women aged ≥ 70 years for treatment.
The proposed new thresholds could identify currently under-recognised high-risk individuals for treatment. It should be considered as a recommendation for osteoporosis management in Australia.
Efficacy, cost, and aspects to take into account in the treatment of osteoporosis in the elderly
2019, Revista Espanola de Geriatria y Gerontologia
Age is one of the principal risk factors for development of frailty fractures. Age pyramids show a population that is becoming increasingly more elderly, with an increasing incidence of fractures, and the forecasts for the future are truly alarming. Adequate handling of these patients who are especially at risk, at both the preventive and care levels, with a well-defined orthogeriatric model is necessary to respond to this clinical challenge. The objective of this review is to analyze the efficacy of the different strategies for the handling of geriatric patients with fracture risk.
La edad es uno de los principales factores de riesgo para desarrollar una fractura por fragilidad. Las pirámides de edad muestran una población cada vez más envejecida y la incidencia de fracturas es cada vez mayor, siendo las previsiones para el futuro verdaderamente preocupantes. Un adecuado manejo de estos pacientes de especial riesgo, tanto a nivel preventivo como asistencial con un modelo ortogeriátrico bien definido se hacen necesarias para hacer frente a este reto clínico. En esta revisión queremos realizar un análisis de la eficacia de las diferentes estrategias de manejo del paciente geriátrico con riesgo de fractura.
Executive summary: Italian guidelines for diagnosis, risk stratification, and care continuity of fragility fractures 2021
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Cost-Effectiveness of the Screening for the Primary Prevention of Fragility Hip Fracture in Spain Using FRAX<sup>®</sup>
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View all citing articles on Scopus

¹: Contributed equally to the manuscript.

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Original articleCost-effectiveness of osteoporosis treatments in postmenopausal women using FRAX™ thresholds for decision

Abstract

Purpose

Objective

Method

Outcomes

Results

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Disclosure of interest

Acknowledgements

Lancet

Bone

Value Health

Health Policy

Value Health

Maturitas

An estimate of the worldwide prevalence and disability associated with osteoporotic fractures

Osteoporos Int

FRAX™ and the assessment of fracture probability in men and women from the UK

Osteoporos Int

European guidance for the diagnosis and management of osteoporosis in postmenopausal women

Osteoporos Int

Challenges for model-based economic evaluations of postmenopausal osteoporosis interventions

Osteoporos Int

Cost-effective osteoporosis treatment thresholds: the United States perspective

Osteoporos Int

National Osteoporosis Guideline Group. Case finding for the management of osteoporosis with FRAX™ – assessment and intervention thresholds for the UK

Osteoporos Int

Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women

JAMA

Consequences of a hip fracture: a prospective study over 1 year

Osteoporos Int

Which screening strategy using BMD measurements would be most cost-effective for hip fracture prevention in elderly women? A decision analysis based on a Markov model

Osteoporos Int

Clinical outcomes and mortality after hip fracture: a 2-year follow-up study

Bone

Hip fractures in institutionalized elderly people: incidence rates and excess mortality

J Bone Miner Res

Meta-analyses of therapies for postmenopausal osteoporosis. IX: summary of meta-analyses of therapies for postmenopausal osteoporosis

Endocr Rev

A systematic review and economic evaluation of alendronate. etidronate. risedronate. raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis

Health Technol Assess

Drug Insight: choosing a drug treatment strategy for women with osteoporosis – an evidence-based clinical perspective

Nat Clin Pract Rheumatol

Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial

JAMA

Original article
Cost-effectiveness of osteoporosis treatments in postmenopausal women using FRAX™ thresholds for decision