The cost-effectiveness of risedronate in the UK for the management of osteoporosis using the FRAX®

Summary  

The study estimated the cost-effectiveness of risedronate compared to no treatment in UK women using the FRAX algorithm for fracture risk assessment. A Markov cohort model was used to estimate the cost-effectiveness. Risedronate was found cost-effective from the age of 65 years, assuming a willingness to pay for a QALY of ￡30,000.     

FRAX® based intervention thresholds for management of osteoporosis in Singaporean women

Summary

Potential FRAX®-based major osteoporotic fracture (MOF) and hip fracture (HF) intervention thresholds (ITs) for postmenopausal Singaporean women were explored. Age-dependent ethnic-specific and weighted mean ITs progressively increased with increasing age. Fixed ITs were derived via discriminatory value analysis. MOF and HF ITs with highest the Youden index were chosen as optimal.

Introduction

We aimed to explore FRAX®-based intervention thresholds (ITs) to potentially guide osteoporosis treatment in Singapore, a multi-ethnic nation.

Method

One thousand and one Singaporean postmenopausal community-dwelling women belonging to Chinese, Malay and Indian ethnicities underwent clinical risk factor (CRF) and BMD assessment. FRAX® major osteoporotic fracture (MOF) and hip fracture (HF) probabilities were calculated using ethnic-specific models. We employed the translational logic adopted by NOGG (UK), whereby osteoporosis treatment is recommended to any postmenopausal woman whose fracture probability based on other CRFs is similar to or exceeds that of an age-matched woman with a fracture. Using the same logic, ethnic-specific and mean weighted age-dependent ITs were computed. Employing these age-dependent ITs as a reference, the performance of fixed (age-independent) ITs were examined using ROC curves and discriminatory analysis, with the highest Youden index (YI) (sensitivity?+?specificity???1) used to identify the optimal MOF and HF ITs.

Results

The mean age was 58.9 (6.9) years. Seven hundred and eighty-nine (79%) women were Chinese, 136 (13.5%) Indian and 76 (7.5%) Malay. Age-dependent MOF ITs ranged from 3.1 to 33%, 2.5 to 17% and 2.5 to 16% whilst HF ITs ranged from 0.7 to 17%, 0.4 to 6% and 0.4 to 6.3% in Chinese, Malay and Indian women, respectively, between the ages of 50 and 90 years. The weighted age-dependent MOF and HF ITs ranged from 2.9% and 0.6%, respectively, at the age of 50, to 28% and 14% at 90 years of age. Fixed MOF/HF ITs of 5.5%/1%, 2.5%/1% and 2.5%/0.25% were identified as the most optimal by the highest YI in Chinese, Malay and Indian women, respectively. Fixed MOFP and HF ITs of 4% and 1%, respectively, were found to be most optimal on the weighted means analysis.

Conclusion

The ITs for osteoporosis treatment in Singapore show marked variations across ethnicities. Weighted mean thresholds may overcome the dilemma of intervening at different thresholds for different ethnicities. Choosing fixed ITs may have to involve trade-offs between sensitivity and specificity. FRAX®-based age-dependent or the fixed intervention thresholds suggested as an alternative to be considered for use in Singapore though further studies on the societal and health economic impacts of choosing these thresholds in Singapore are needed.

     

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

PurposeFRAX? 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.ObjectiveOur objective was to evaluate the cost-effectiveness of five years of branded alendronate therapy in postmenopausal French women with a known FRAX? score.MethodA 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%.OutcomesNumber of women to treat (NNT) for preventing hip fracture, costs, quality-adjusted life-years, incremental cost-effectiveness ratios.ResultsThe 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.ConclusionUsing 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.     

The effects of a FRAX® revision for the USA

Summary

A revision (version 3.0) of the fracture risk assessment tool (FRAX^®) is developed based on an update of epidemiological information for the USA. With the revised tool, there were strong correlations (r?>?0.99) between versions 2.0 and 3.0 for FRAX^® estimates of fracture probability, but the revised models gave lower probability estimates.

Introduction

The aim of this study was to determine the effects of a revision of the epidemiological data used to compute fracture probabilities in the USA with FRAX^®.

Methods

Models were constructed to compute fracture probabilities based on updated fracture incidence and mortality rates in the USA. The models comprised the ten-year probability of hip fracture and the ten-year probability of a major osteoporotic fracture, both including femoral neck bone mineral density (BMD). For each model, fracture and death hazards were computed as continuous functions. The effect of the revised rates on fracture probability was examined by piecewise linear regression using multiple combinations of clinical risk factors and BMD.

Results

At all ages, there was a strong correlation (r?>?0.99) between version 2.0 and revised FRAX^® estimates of fracture probability. For a major osteoporotic fracture, the revised model gave lower median probabilities by 13% to 24% in men, depending on age, and by 19% to 24% in women. For hip fracture probability, the revised model gave lower median fracture probabilities by 40% and 27% at the ages of 50 and 60 years in men and by 43% and 30%, respectively, in women. At the ages of 70 years and older the revised model gave similar hip fracture probabilities as version 2.0 in both men and women.

Conclusion

The revised FRAX^® model for the USA (version 3.0) does not alter the ranking of fracture probabilities but provides lower probability estimates than version 2.0, particularly, in younger women and men.     

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

BackgroundAn 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.MethodsThe 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.ResultsThe 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.DiscussionFRAX^® 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 bazedoxifene incorporating the FRAX® algorithm in a European perspective

Summary

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.     

Updated fracture incidence rates for the Italian version of FRAX®

Summary

In order to update data underlying the Italian version of FRAX, we computed the national hip fracture incidence in Italy from hospitalization records for the year 2008. Mortality data and 10-year probabilities of major osteoporotic fractures were also updated. This revision will improve FRAX accuracy and reliability.

Introduction

The original Italian version of FRAX® was based on five regional estimates of hip fracture risk undertaken up to 20 years previously. Our objective was to update hip fracture rates for the model with more recently derived data from the whole Italian population and more recent data on mortality.

Methods

We analyzed the Italian national hospitalization database for the year 2008 in order to compute age- and sex-specific hip fracture incidence rates. Re-hospitalisations of the same patients within 1 year were excluded from the analysis. Hip fracture incidence rates were computed for the age range of 40–100 years, whereas the original FRAX model lacked data on the youngest and oldest age groups. In addition, we used the national mortality data for the same year 2008 to update the model. Ten-year fracture probabilities were re-calculated on the basis of the new fracture incidence rates.

Results

The new hip fracture age- and sex-specific incidence rates were close to those used in the original FRAX tool, although some significant differences (not exceeding 25–30 %) were found for men aged 65–75 years and women under 55 years of age. In general, the revision resulted in decreased estimated 10-year probabilities in the younger age groups, whilst those in the older age groups were slightly increased.

Conclusions

The Italian version of FRAX has been updated using the new fracture incidence rates. The impact of these revisions on FRAX is likely to increase the accuracy and reliability of FRAX in estimating 10-year fracture probabilities.     

Updated fracture incidence rates for the US version of FRAX®

Summary

On the basis of updated fracture and mortality data, we recommend that the base population values used in the US version of FRAX® be revised. The impact of suggested changes is likely to be a lowering of 10-year fracture probabilities.

Introduction

Evaluation of results produced by the US version of FRAX® indicates that this tool overestimates the likelihood of major osteoporotic fracture. In an attempt to correct this, we updated underlying fracture and mortality rates for the model.

Methods

We used US hospital discharge data from 2006 to calculate annual age- and sex-specific hip fracture rates and age-specific ratios to estimate clinical vertebral fracture rates. To estimate the incidence of any one of four major osteoporotic fractures, we first summed these newly derived hip and vertebral fracture estimates with Olmsted County, MN, wrist and upper humerus fracture rates, and then applied 10–20% discounts for overlap.

Results

Compared with rates used in the current FRAX® tool, 2006 hip fracture rates are about 16% lower, with greatest reductions observed among those below age 65 years; major osteoporotic fracture rates are about one quarter lower, with similar reductions across all ages.

Conclusions

We recommend revising the US-FRAX by updating current base population values for hip fracture and major osteoporotic fracture. The impact of these revisions on FRAX® is likely to be lowering of 10-year fracture probabilities, but more precise estimates of the impact of these changes will be available after these new rates are incorporated into the FRAX® tool.     

Treatment thresholds for osteoporosis in men on androgen deprivation therapy: T-score versus FRAX™

Summary  

Men treated by androgen deprivation therapy (ADT) for localized prostate cancer are at risk for fracture, but it is not known which men require pharmacologic treatment. We found that 33% of men on ADT had osteoporosis of spine, hip, or forearm by dual-energy X-ray absorptiometry (DXA), thus requiring treatment. Using the new fracture prediction algorithm (FRAX™) tool with corrected femoral neck T-score identified only 17% requiring treatment, and, if calculated without femoral neck, 54% were identified to need treatment.     

A randomized comparison of the GlideRite® Rigid Stylet to a malleable stylet for orotracheal intubation by novices using the GlideScope®

Purpose

A stylet is usually necessary when using the GlideScope^® videolaryngoscope for orotracheal intubation. A special stylet, the GlideRite^® Rigid Stylet (GRS), was designed for this purpose. A previous trial involving experienced operators showed that the GRS offered no performance improvement vs a standard malleable stylet (SMS). In our trial, we compared the performance of the GRS with that of the SMS in terms of time to intubation and ease of intubation when used by novice GlideScope^® operators.

Methods

Sixty patients with normal-appearing airways requiring orotracheal intubation for elective surgery were randomly allocated to be intubated by novice operators with the GlideScope^®, using either the GRS or the SMS. Time to intubation was assessed by a blinded observer, and the operators were blinded until just prior to tracheal intubation. Ease of intubation was assessed by a five-point ordinal scale (from 1- easy to 5 -difficult). Intubation attempts/failures, glottic grades, and usage of external laryngeal manipulation were recorded.

Results

There were no significant differences between the GRS and the SMS in terms of the median time to intubation (60 sec, interquartile range [IQR] 48-75 vs 61 sec, IQR 49-75, respectively; P = 0.94) and the ease of intubation (GRS median score: 1.5, IQR 1-2 vs SMS median score: 1, IQR 1-2; P = 0.94). There were no other significant differences between groups.

Conclusion

The GRS and the SMS have similar performance characteristics when used by novice operators for GlideScope^®-assisted orotracheal intubation. (Registered at ClinicalTrials.gov: NCT00884754).     

Construction of a FRAX? model for the assessment of fracture probability in Canada and implications for treatment

Summary

We describe the creation of a FRAX? model for the assessment of fracture probability in Canadian men and women, calibrated from national hip fracture and mortality data. This FRAX tool was used to examine possible thresholds for therapeutic intervention in Canada in two large complementary cohorts of women and men.

Objective

To evaluate a Canadian World Health Organization (WHO) fracture risk assessment (FRAX?) tool for computing 10-year probabilities of osteoporotic fracture.

Methods

Fracture probabilities were computed from national hip fracture data (2005) and death hazards (2004) for Canada. Probabilities took account of age, sex, clinical risk factors (CRFs), and femoral neck bone mineral density (BMD). Treatment implications were studied in two large cohorts of individuals age 50?years and older: the population-based Canadian Multicentre Osteoporosis Study (4,778 women and 1,919 men) and the clinically referred Manitoba BMD Cohort (36,730 women and 2,873 men).

Results

Fracture probabilities increased with age, decreasing femoral neck T-score, and number of CRFs. Among women, 10.1?C11.3% would be designated high risk based upon 10-year major osteoporotic fracture probability exceeding 20%. A much larger proportion would be designated high risk based upon 10-year hip fracture probability exceeding 3% (25.7?C28.0%) or osteoporotic BMD (27.1?C30.9%), and relatively few from prior hip or clinical spine fracture (1.6?C4.2%). One or more criteria for intervention were met by 29.2?C34.0% of women excluding hip fracture probability (35.3?C41.0% including hip fracture probability). Lower intervention rates were seen among CaMos (Canadian Multicentre Osteoporosis Study) men (6.8?C12.9%), but in clinically referred men from the Manitoba BMD Cohort, one or more criteria for high risk were seen for 26.4% excluding hip fracture probability (42.4% including hip fracture probability).

Conclusions

The FRAX tool can be used to identify intervention thresholds in Canada. The FRAX model supports a shift from a dual X-ray absorptiometry (DXA)-based intervention strategy, towards a strategy based on fracture probability for a major osteoporotic fracture.