Good research practices for measuring drug costs in cost-effectiveness analyses: a societal perspective: the ISPOR Drug Cost Task Force report--Part II.

OBJECTIVES: Major guidelines regarding the application of cost-effectiveness analysis (CEA) have recommended the common and widespread use of the "societal perspective" for purposes of consistency and comparability. The objective of this Task Force subgroup report (one of six reports from the International Society for Pharmacoeconomics and Outcomes Research [ISPOR] Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis [Drug Cost Task Force (DCTF)]) was to review the definition of this perspective, assess its specific application in measuring drug costs, identify any limitations in theory or practice, and make recommendations regarding potential improvements. METHODS: Key articles, books, and reports in the methodological literature were reviewed, summarized, and integrated into a draft review and report. This draft report was posted for review and comment by ISPOR membership. Numerous comments and suggestions were received, and the report was revised in response to them. RESULTS: The societal perspective can be defined by three conditions: 1) the inclusion of time costs, 2) the use of opportunity costs, and 3) the use of community preferences. In practice, very few, if any, published CEAs have met all of these conditions, though many claim to have taken a societal perspective. Branded drug costs have typically used actual acquisition cost rather than the much lower social opportunity costs that would reflect only short-run manufacturing and distribution costs. This practice is understandable, pragmatic, and useful to current decision-makers. Nevertheless, this use of CEA focuses on static rather than dynamic efficacy and overlooks the related incentives for innovation. CONCLUSIONS: Our key recommendation is that current CEA practice acknowledge and embrace this limitation by adopting a new standard for the reference case as one of a "limited societal" or "health systems" perspective, using acquisition drug prices while including indirect costs and community preferences. The field of pharmacoeconomics also needs to acknowledge the limitations of this perspective when it comes to important questions of research and development costs, and incentives for innovation.

Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases.

OBJECTIVE: To characterize the relationships between adherence (complance and persistence) to bisphosphonate therapy and risk of specific fracture types in postmenopausal women. PATIENTS AND METHODS: Data were collected from 45 employers and 100 health plans in the continental United States from 2 claims databases during a 5-year period (January 1, 1999, through December 31, 2003). Claims from patients receiving a bisphosphonate prescription (alendronate or risedronate) were evaluated for 6 months before the Index prescription and during 24 months of follow-up to determine total, vertebral, and nonvertebral osteoporotic fractures, persistence (no gap in refills for >30 days during 24 months), and refill compliance (medication possession ratio > or = 0.80). RESULTS: The eligible cohort included 35,537 women (age, > or = 45 years) who received a bisphosphonate prescription. A subgroup with a specified diagnosis of postmenopausal osteoporosis was also evaluated. Forty-three percent were refill compliant, and 20% persisted with bisphosphonate therapy during the 24-month study period. Total, vertebral, nonvertebral, and hip fractures were significantly lower in refill-compliant and persistent patients, with relative risk reductions of 20% to 45%. The relationship between adherence and fracture risk remained significant after adjustment for baseline age, concomitant medications, and fracture history. There was a progressive relationship between refill compliance and fracture risk reduction, commencing at refill compliance rates of approximately 50% and becoming more pronounced at compliance rates of 75% and higher. CONCLUSIONS: Adherence to bisphosphonate therapy was associated with significantly fewer fractures at 24 months. Increasing refill compliance levels were associated with progressively lower fracture rates. These findings suggest that incremental changes in medication-taking habits could improve clinical outcomes of osteoporosis treatment.

Evaluation of three population-based strategies for fracture prevention: results of the osteoporosis population-based risk assessment (OPRA) trial.

BACKGROUND: The integration of bone density testing into well-designed fracture prevention programs that can be applied in populations has not been studied. OBJECTIVES: We sought to compare the outcomes of 3 strategies for allocating bone density testing within an HMO-based fracture prevention program. RESEARCH DESIGN: Women were randomly sampled and allocated to one of 3 groups: (1) a universal group, in which all were offered bone mineral density (BMD) testing (1986 contacted; 415 participated); 2) the SCORE group, in which women scoring > or = 7 on the SCORE questionnaire were invited for BMD testing (1940 contacted; 576 participated); and (3) the Study of Osteoporotic Fracture (SOF)-based group, in which women with > or = 5 hip fracture risk factors were invited for BMD testing (5342 contacted; 2176 participated). SUBJECTS: Women aged 60-80 not taking hormone therapy or osteoporosis medication were included. MEASURES: Outcomes ascertained during 33 months of follow-up in all women contacted included initiation of osteoporosis treatment and hip and total fracture rates. Outcomes evaluated among all participants included changes in fracture risk factors, osteoporosis knowledge, and satisfaction with the program. RESULTS: Osteoporosis treatment rates did not differ among all women contacted but were slightly higher among trial participants in the universal and SCORE groups (21.1% and 20.2%, respectively; versus 16.7% in the SOF-based group (P value versus universal = 0.04). Among all women contacted, fracture rates were lowest in the universal group (74.11/1000) and differed significantly compared with the SCORE (99.44/1000; P = 0.009) and SOF-based groups (91.77/1000;P = 0.02). Knowledge about osteoporosis risk factors was highest in the universal group and lowest in the SOF-based group (P < 0.01). CONCLUSIONS: The degree to which BMD testing was offered to women in a fracture prevention program significantly affected total fracture rates, change in some fracture risk factors, and knowledge about risk factors.

Osteoporosis and fracture risk in women of different ethnic groups.

UNLABELLED: Osteoporosis and 1-year fracture risk were studied in 197,848 postmenopausal American women from five ethnic groups. Weight explained differences in BMD, except among blacks, who had the highest BMD. One SD decrease in BMD predicted a 50% increased fracture risk in each group. Despite similar relative risks, absolute fracture rates differed. INTRODUCTION: Most information about osteoporosis comes from studies of white women. This study describes the frequency of osteoporosis and the association between BMD and fracture in women from five ethnic groups. MATERIALS AND METHODS: This study was made up of a cohort of 197,848 community-dwelling postmenopausal women (7784 blacks, 1912 Asians, 6973 Hispanics, and 1708 Native Americans) from the United States, without known osteoporosis or a recent BMD test. Heel, forearm, or finger BMD was measured, and risk factor information was obtained; 82% were followed for 1 year for new fractures. BMD and fracture rates were compared, adjusting for differences in covariates. RESULTS: By age 80, more than one-fifth of women in each ethnic group had peripheral BMD T scores <-2.5. Black women had the highest BMD; Asian women had the lowest. Only the BMD differences for blacks were not explained by differences in weight. After 1 year, 2414 new fractures of the spine, hip, forearm, wrist, or rib were reported. BMD at each site predicted fractures equally well within each ethnic group. After adjusting for BMD, weight, and other covariates, white and Hispanic women had the highest risk for fracture (relative risk [RR] 1.0 [referent group] and 0.95, 95% CI, 0.76, 1.20, respectively), followed by Native Americans (RR, 0.87; 95% CI, 0.57, 1.32), blacks (RR, 0.52; 95% CI, 0.38, 0.70), and Asian Americans (RR, 0.32; 95% CI, 0.15, 0.66). In age- and weight-adjusted models, each SD decrease in peripheral BMD predicted a 1.54 times increased risk of fracture in each ethnic group (95% CI, 1.48-1.61). Excluding wrist fractures, the most common fracture, did not materially change associations. CONCLUSIONS: Ethnic differences in BMD are strongly influenced by body weight; fracture risk is strongly influenced by BMD in each group. Ethnic differences in absolute fracture risk remain, which may warrant ethnic-specific clinical recommendations.

Predictive value of low BMD for 1-year fracture outcomes is similar for postmenopausal women ages 50-64 and 65 and Older: results from the National Osteoporosis Risk Assessment (NORA).

UNLABELLED: The relationship of low bone mass and fracture in younger postmenopausal women has not been extensively studied. In a large cohort of postmenopausal women > or =50 years of age, we found the relationship of BMD measured at peripheral sites and subsequent 1-year fracture risk to be similar between women <65 and those > or =65 years of age. INTRODUCTION: Low bone mass and fractures are prevalent in older postmenopausal women. However, the frequency of low bone mass and fracture in younger postmenopausal women has not been studied extensively. There are very limited data regarding the association between BMD measurements and fractures in postmenopausal women who are between the ages of 50 and 64. MATERIALS AND METHODS: In the National Osteoporosis Risk Assessment (NORA) we studied the frequency of low bone mass and its association with fracture in women 50-64 years of age in comparison with women > or =65 of age. NORA enrolled 200,160 postmenopausal women > or =50 years of age who had no prior diagnosis of osteoporosis. Baseline BMD was measured at the heel, forearm, or finger. A 1-year follow-up survey requesting incident fractures since baseline was completed by 163,935 women, 87,594 (53%) of whom were 50-64 years of age. The association between BMD and fracture was assessed using logistic regression, adjusted for important covariates. RESULTS: Thirty-one percent of women 50-64 years of age had low bone mass (T scores < or = -1.0) compared to 62% of women > or =65 years of age. During the first year of follow-up, 2440 women reported fractures of wrist/forearm, rib, spine, or hip, including 440 hip fractures. Nine hundred four women 50-64 years of age reported fractures, including 86 hip fractures, accounting for 37% of fractures and 20% of hip fractures reported in the entire NORA cohort. Relative risk for osteoporotic fracture was 1.5 for each SD decrease in BMD for both the younger and older groups of women. CONCLUSION: Low BMD in younger postmenopausal women 50-64 years of age showed a 1-year relative risk of fracture similar to that found in women > or =65 years of age.

Bone mineral density thresholds for pharmacological intervention to prevent fractures.

BACKGROUND: Treatment intervention thresholds for prevention of osteoporotic fractures can be derived from reports from the World Health Organization (diagnostic criteria) and National Osteoporosis Foundation (treatment criteria). It is not known how well these thresholds work to identify women who will fracture and are therefore candidates for treatment interventions. We used data from the National Osteoporosis Risk Assessment (NORA) to examine the effect of different treatment thresholds on fracture incidence and numbers of women with fractures within the year following bone mineral density measurement. METHODS: The study comprised 149 524 white postmenopausal women aged 50 to 104 years (mean age, 64.5 years). At baseline, bone mineral density was assessed by peripheral bone densitometry at the heel, finger, or forearm. New fractures during the next 12 months were self-reported. RESULTS: New fractures were reported by 2259 women, including 393 hip fractures; only 6.4% had baseline T scores of -2.5 or less (World Health Organization definition for osteoporosis). Although fracture rates were highest in these women, they experienced only 18% of the osteoporotic fractures and 26% of the hip fractures. By National Osteoporosis Foundation treatment guidelines, 22.6% of the women had T scores of 2.0 or less, or -1.5 or less with 1 or more clinical risk factors. Fracture rates were lower, but 45% of osteoporotic fractures and 53% of hip fractures occurred in these women. CONCLUSIONS: Using peripheral measurement devices, 82% of postmenopausal women with fractures had T scores better than -2.5. A strategy to reduce overall fracture incidence will likely require lifestyle changes and a targeted effort to identify and develop treatment protocols for women with less severe low bone mass who are nonetheless at increased risk for future fractures.

An approach to identifying osteopenic women at increased short-term risk of fracture.

BACKGROUND: Identification and management of women to reduce fractures is often limited to T scores less than -2.5, although many fractures occur with higher T scores. We developed a classification algorithm that identifies women with osteopenia (T scores of -2.5 to -1.0) who are at increased risk of fracture within 12 months of peripheral bone density testing. METHODS: A total of 57 421 postmenopausal white women with baseline peripheral T scores of -2.5 to -1.0 and 1-year information on new fractures were included. Thirty-two risk factors for fracture were entered into a classification and regression tree analysis to build an algorithm that best predicted future fracture events. RESULTS: A total of 1130 women had new fractures in 1 year. Previous fracture, T score at a peripheral site of -1.8 or less, self-rated poor health status, and poor mobility were identified as the most important determinants of short-term fracture. Fifty-five percent of the women were identified as being at increased fracture risk. Women with previous fracture, regardless of T score, had a risk of 4.1%, followed by 2.2% in women with T scores of -1.8 or less or with poor health status, and 1.9% for women with poor mobility. The algorithm correctly classified 74% of the women who experienced a fracture. CONCLUSIONS: This classification tool accurately identified postmenopausal women with peripheral T scores of -2.5 to -1.0 who are at increased risk of fracture within 12 months. It can be used in clinical practice to guide assessment and treatment decisions.

Evaluation of decision rules to identify postmenopausal women for intervention related to osteoporosis.

Decision rules for intervention that utilize screening tools for bone mineral density (BMD) testing and incorporating the BMD findings and other risk factors to identify high-risk women to prevent fracture have not been evaluated. We examine the sensitivity and specificity of decision rules for intervention based on two pre-BMD screening tools: Simple Calculated Osteoporosis Risk Estimation (SCORE) and a Study of Osteoporotic Fractures (SOF)-based tool. Women 60 years of age and older without previous osteoporosis diagnosis were randomly selected from a managed care population and invited to receive a BMD test. Four hundred sixteen women had complete information and were included in the study. Women were classified as high risk requiring intervention using three different criteria: World Health Organization (t-score -2.5 or less), National Osteoporosis Foundation (t-score -2.0 or less, or -1.5 or less with one or more risk factors), and the SOF-based criteria (prior fracture; or age 60-64 with t-score less than -2.5 or age 65 or older with z-score less than -0.43 and five or more risk factors). SCORE identified 82% of the women as appropriate for BMD testing, whereas the SOF-based tool identified 26%. Sensitivity and specificity were 89.8%-96.5% and 23.8%-34.8%, respectively, for the decision rule using SCORE as the screening tool and 30.5%-84.9% and 76.0%-95.8%, respectively, for the decision rule based on SOF screening criteria. SCORE correctly identified more women who were at high risk for intervention, whereas the SOF-based tool correctly identified more women who do not meet intervention criteria. The appropriate selection of a screening tool depends upon the objective for intervention and trade-off between not identifying women for BMD testing who are at high risk and identifying more women for BMD testing who are at low risk.

Management of osteoporosis in women aged 50 and older with osteoporosis-related fractures in a managed care population.

This study describes the pattern of evaluation and management of osteoporosis in women aged 50 and older following an osteoporosis-related fracture, conducted as a retrospective cohort study using the administrative claims database of a managed care organization. Subjects were women, aged 50 years and older, with at least one osteoporosis-related fracture in the years 1996-1998 who were continuously enrolled in the system's health plan for at least 6 months prior to and post-fracture. Bone mineral density (BMD) testing, diagnosis of osteoporosis, and treatment with any Food and Drug Administration-approved medication for osteoporosis were identified using CPT, ICD-9, and National Drug Codes for the 6-month post-fracture period. There were 658 women with an osteoporosis-related fracture: 189 (29%) hip fractures, 226 (34%) wrist fractures, 127 (19%) vertebral fractures, and 116 (18%) rib fractures. In the post-fracture period, 46 (7%) underwent BMD testing, 153 (23%) had a diagnosis of osteoporosis, and 220 (31%) were treated with a medication approved for the prevention or treatment of osteoporosis. Of the 220 women with medication claims, 124 (56%) were for estrogen, and 96 (44%) were for other antiresorptive agents. Of the 507 women who did not have medication claims during the 6 months prior to the fracture, only 17% had new fills after the fracture. Management of osteoporosis in women aged 50 and older with fractures was inadequate, despite the high risk of subsequent fractures and recommendations that osteoporosis be the presumptive diagnosis. Significant opportunity exists for improvement in assuring post-fracture followup care.

Recency and duration of postmenopausal hormone therapy: effects on bone mineral density and fracture risk in the National Osteoporosis Risk Assessment (NORA) study.

OBJECTIVES: Results from the Women's Health Initiative showed that postmenopausal hormone replacement therapy (HRT) prevents fractures but has an overall unfavorable risk:benefit ratio, leading to the recommendation that HRT be used only for women with troublesome menopause symptoms, and for as short a time as possible. This recommendation has important implications for the timing and duration of HRT and the prevention of osteoporosis. The large number of women participating in the National Osteoporosis Risk Assessment (NORA) program provided the opportunity to evaluate bone mineral density (BMD) and 1-year fracture risk in analyses stratified by duration and recency of HRT. DESIGN: Participants were 170,852 postmenopausal women aged 50 to 104, without known osteoporosis, who were recruited from primary physicians offices across the US. BMD was measured at one of four peripheral sites, and the 1-year risk of osteoporotic fracture was assessed by questionnaire. RESULTS: At baseline, current HRT users had the highest T-scores at every age. Among current hormone users, women who had used HRT longest had the highest BMD levels. Women who had stopped HRT more than 5 years previously, regardless of duration of use, had T-scores similar to never-users. Current but not past hormone use at baseline was associated with a 25% to 29% lower risk of osteoporotic fracture (P < 0.0001) in 1 year, compared with nonusers. These findings were independent of age, ethnicity, body mass index, lifestyle, years postmenopausal, and site of BMD measurement. CONCLUSIONS: We conclude that postmenopausal BMD and fracture are closely associated with current, but not prior, HRT use. Use of HRT for 5 years or less, as proposed for treatment of symptomatic women during menopause transition, is unlikely to preserve bone or significantly reduce fracture risk in later years.

Evaluation and management of osteoporosis following hospitalization for low-impact fracture.

OBJECTIVE: To evaluate the pattern of osteoporosis evaluation and management in postmenopausal women who present with low-impact (minimal trauma) fracture. DESIGN: Retrospective chart review of patients admitted with a fracture in the absence of trauma or bone disease. Telephone follow-up survey was conducted at 12 months after discharge to collect information on physician visits, pharmacological therapies for osteoporosis, functional status, and subsequent fractures. PATIENTS/PARTICIPANTS: Postmenopausal women admitted to a hospital in St. Paul, Minnesota between June 1996 and December 1997 for low-impact fractures were identified. Low-impact fracture was defined as a fracture occurring spontaneously or from a fall no greater than standing height. Retrospective review of 301 patient medical records was conducted to obtain data on pre-admission risk factors for osteoporosis and/or fracture, and osteoporosis-related evaluation and management during the course of hospitalization. Follow-up 1 year after the incident fracture was obtained on 227 patients. MEASUREMENTS AND MAIN RESULTS: Two hundred twenty-seven women were included in the study. Osteoporosis was documented in the medical record in 26% (59/227) of the patients at hospital discharge. Within 12 months of hospital discharge, 9.6% (22/227) had a bone mineral density test, and 26.4% (60/227) were prescribed osteoporosis treatment. Of those who were prescribed osteoporosis treatment, 86.6% (52/60) remained on therapy for 1 year. Nineteen women suffered an additional fracture. Compared to women without a prior fracture, women with at least 1 fracture prior to admission were more likely to have osteoporosis diagnosed and to receive osteoporosis-related medications. CONCLUSION: Despite guidelines that recommend osteoporosis evaluation in adults experiencing a low-trauma fracture, we report that postmenopausal women hospitalized for low-impact fracture were not sufficiently evaluated or treated for osteoporosis during or after their hospital stay. There are substantial opportunities for improvement of care in this high-risk population to prevent subsequent fractures.

Prediction of fracture risk in postmenopausal white women with peripheral bone densitometry: evidence from the National Osteoporosis Risk Assessment.

Low bone mineral density (BMD) is a risk factor for fracture. Although the current "gold standard" test is DXA of the hip and spine, this method is not universally available. No large studies have evaluated the ability of new, less expensive peripheral technologies to predict fracture. We studied the association between BMD measurements at peripheral sites and subsequent fracture risk at the hip, wrist/forearm, spine, and rib in 149,524 postmenopausal white women, without prior diagnosis of osteoporosis. At enrollment, each participant completed a risk assessment questionnaire and had BMD testing at the heel, forearm, or finger. Main outcomes were new fractures of the hip, wrist/forearm, spine, or rib within the first 12 months after testing. After 1 year, 2259 women reported 2340 new fractures. Based on manufacturers' normative data and multivariable adjusted analyses, women who had T scores < or = -2.5 SD were 2.15 (finger) to 3.94 (heel ultrasound [US]) times more likely to fracture than women with normal BMD. All measurement sites/devices predicted fracture equally well, and risk prediction was similar whether calculated from the manufacturers' young normal values (T scores) or using SDs from the mean age of the National Osteoporosis Risk Assessment (NORA) population. The areas under receiver operating characteristic (ROC) curves for hip fracture were comparable with those published using measurements at hip sites. We conclude that low BMD found by peripheral technologies, regardless of the site measured, is associated with at least a twofold increased risk of fracture within 1 year, even at skeletal sites other than the one measured.