Hip and other fragility fracture incidence in real-world teriparatide-treated patients in the United States.

This study demonstrates real-world effectiveness of teriparatide in reducing the risk of hip and other fragility fractures. Fracture incidence significantly decreased as adherence and persistence increased for any clinical, vertebral, nonvertebral, and hip fractures among patients who were observed for 2 years after teriparatide initiation. INTRODUCTION: Examine the relationship of treatment adherence and persistence to teriparatide with hip and other fractures. METHODS: Truven MarketScan Research Databases, 2004 through 2014, provided teriparatide users ≥18 years old with continuous coverage 12 months pre- and 24 months post-teriparatide prescription. Adherence (medication possession ratio, MPR) groups were defined as high (≥0.80), medium (0.50 ≤ MPR < 0.80), and low (<0.50). Persistence, allowing for ≤90-day gaps between prescriptions, was defined as 1-6, 7-12, 13-18, and 19-24 months. Fracture incidence was summarized and compared by using ANOVA and logistic regression models; the effects of adherence were examined with Cox proportional hazard models with time-dependent covariates for teriparatide exposure. RESULTS: Among 14,284 teriparatide subjects, mean age was 68.4 years, 89.8% were female, and 29.6% had a fracture in the previous year; these characteristics were similar across MPR and persistence groups. The effects of adherence and persistence to teriparatide were statistically significant (P < .001) for all fracture types except wrist (P ≥ .125). By logistic regression, high vs low adherence was associated with reduced risk for any (OR = 0.67; P < .001); vertebral (OR = 0.64; P < .001); nonvertebral (OR = 0.71; P < .001); and hip fractures (OR = 0.52; P < .001) and longer (19-24 months) vs shorter persistence (1-6 months) was associated with reduced risk for any (OR = 0.63, P < .001); vertebral (OR = 0.56, P < .001); nonvertebral (OR = 0.69, P < .001); and hip fractures (OR = 0.48, P < .001). Cox models revealed a significantly reduced risk between high and low adherence for any (OR = 0.69, P < .001); vertebral (OR = 0.60, P < .001); nonvertebral (OR = 0.77, P < .001); and hip fractures (OR = 0.55, P < .001). CONCLUSION: Fracture incidence significantly decreased as persistence and adherence to teriparatide increased.

FRAX and the effect of teriparatide on vertebral and non-vertebral fracture.

UNLABELLED: Daily teriparatide injections have been shown to reduce vertebral and non-vertebral fractures. Here, we demonstrate that the magnitude of fracture risk reduction is independent of baseline fracture probability assessed by FRAX. INTRODUCTION: Daily administration of 20 or 40 µg teriparatide has been shown to significantly decrease the risk of vertebral and non-vertebral fracture compared with placebo. The aim of the present study was to evaluate fracture risk assessed at baseline using the FRAX® tool and to determine the efficacy of teriparatide as a function of baseline fracture risk. METHODS: One thousand six hundred thirty-seven postmenopausal women in the pivotal phase three trial, randomly assigned to receive placebo (n = 544), teriparatide 20 µg per day (n = 541) or teriparatide 40 µg per day (n = 552), were studied. Baseline clinical risk factors were entered into country-specific FRAX models to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. Because there was no difference in effect of 20 and 40 µg teriparatide daily on fracture occurrence, the two active groups were merged. The interaction between probability of a major fracture and treatment efficacy was examined by Poisson regression. RESULTS: The 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.2-67.2 %. Treatment with teriparatide was associated with a 37 % decrease in all non-vertebral fractures (95 % CI 10-56 %) and a 56 % decrease in low-energy non-vertebral fractures (95 % CI 24-75 %) compared with placebo. The risk of morphometric vertebral fractures decreased significantly by 66 % (95 % CI 50-77 %). Hazard ratios for the effect of teriparatide on the fracture outcome did not change significantly with increasing fracture probability (p > 0.30). Similar findings were noted for the interaction when BMD was excluded from the FRAX model, or when probability of hip fracture was used as the marker of baseline risk. CONCLUSION: We conclude that teriparatide significantly decreases the risk of non-vertebral and morphometric vertebral fractures in women by a similar extent, irrespective of baseline fracture probability.

The effect of teriparatide compared with risedronate on reduction of back pain in postmenopausal women with osteoporotic vertebral fractures.

UNLABELLED: The effect of teriparatide and risedronate on back pain was tested, and there was no difference in the proportion of patients experiencing a reduction in back pain between groups after 6 or 18 months. Patients receiving teriparatide had greater increases in bone mineral density and had fewer vertebral fractures. INTRODUCTION: This study aimed to understand the effect of teriparatide in reducing back pain in patients with prevalent back pain and vertebral fracture compared to risedronate. METHODS: In an 18-month randomized, double-blind, double-dummy trial, we investigated the effects of teriparatide (20 µg/day) vs. risedronate (35 mg/week) in postmenopausal women with back pain likely due to vertebral fracture. The primary objective was to compare the proportion of subjects reporting ≥30% reduction in worst back pain severity from baseline to 6 months as assessed by a numeric rating scale in each treatment group. Pre-specified secondary and exploratory outcomes included assessments of average and worst back pain at additional time points, disability and quality of life, bone mineral density, incidence of fractures, and safety. RESULTS: At 6 months, 59% of teriparatide and 57% of risedronate patients reported ≥30% reduction in worst back pain and there were no differences between groups in the proportion of patients experiencing reduction in worst or average back pain at any time point, disability, or quality of life. There was a greater increase from baseline in bone mineral density at the lumbar spine (p = 0.001) and femoral neck (p = 0.02) with teriparatide compared to risedronate and a lower incidence of vertebral fractures at 18 months (4% teriparatide and 9% risedronate; p = 0.01). Vertebral fractures were less severe (p = 0.04) in the teriparatide group. There was no difference in the overall incidence of adverse events. CONCLUSIONS: Although there were no differences in back pain-related endpoints, patients receiving teriparatide had greater skeletal benefit than those receiving risedronate.

The impact of teriparatide adherence and persistence on fracture outcomes.

UNLABELLED: The study investigated the real-world relationship between teriparatide adherence and persistence and fracture outcomes in a US claims database. Fracture risk was estimated to decrease as adherence and persistence increased for any clinical, vertebral, and non-vertebral fractures. Greater emphasis on programs to increase patient adherence may improve clinical outcomes. INTRODUCTION: Adherence to osteoporosis treatment is essential for achieving optimal therapeutic outcomes. Previous findings from clinical trials and observational studies demonstrate that longer teriparatide (TPTD) exposure is associated with fewer fractures. The study aim was to investigate real-world relationships between TPTD adherence and persistence and fracture outcomes. METHODS: The Thomson Reuters MarketScan® database, 2004-2008, was used to identify TPTD users with continuous enrollment 12 months pre- and 24 months post-TPTD initiation. Post-index fractures included vertebral and non-vertebral. Adherence (medication possession ratio, MPR) groups were defined as high (MPR ≥ 0.80), medium (0.5 ≤ MPR < 0.8), and low (MPR < 0.5). Persistence groups were defined by periods 1-6, 7-12, 13-18, and 19-24 months. Logistic regressions modeled fracture risk for any clinical, hip, vertebral, and non-vertebral fractures, controlling for patient characteristics, insurance and healthcare provider types, Charlson comorbidity index, bone mineral density screening, medication use, and fracture history. RESULTS: Among 3,587 TPTD patients (mean age 68.9 years; 91% female), fracture risk was lowest in high MPR patients in all models except hip (OR = 1.17; p = 0.64). Medium versus high MPR was a significant risk factor for any fracture (OR = 1.49; p = 0.004) and non-vertebral fracture (OR = 1.45; p = 0.014); low-MPR was a significant risk factor for any fracture (OR = 1.64; p < 0.01), vertebral fracture (OR = 2.56; p = 0.001), and non-vertebral fracture (OR = 1.44; p = 0.013). Persistence of 1-6 months versus 19-24 months was associated with higher risk for any clinical (OR = 1.88, p < 0.001), vertebral (OR = 3.69; p < 0.001), and non-vertebral fracture (OR = 1.51; p = 0.011), but not hip (OR = 1.93; p = 0.08). CONCLUSIONS: Fracture risk decreased as TPTD adherence and persistence increased for any clinical, vertebral, and non-vertebral fractures.

Prevalence and costs of osteoporotic patients with subsequent non-vertebral fractures in the US.

UNLABELLED: This study assesses prevalence of subsequent fractures during the year after incident osteoporosis-related non-vertebral fractures among privately insured and Medicare populations and compares costs between patients with and without subsequent fractures. Many non-vertebral fracture patients incur subsequent fractures, and those who do are significantly more costly during the year after incident fracture. INTRODUCTION: To estimate the prevalence of subsequent osteoporosis-related non-vertebral (NV) fractures during the year following an incident NV fracture and compare costs between NV fracture patients with and without subsequent fractures. METHODS: Using insurance claims data (1999-2006), privately-insured (ages 18-64 years) and Medicare (ages 65+ years) patients with ≥1 subsequent osteoporosis-related NV fracture within a year of an incident osteoporosis-related NV fracture were matched to controls with incident NV fractures but no subsequent fractures. Subsequent fractures were identified as any claim for an NV fracture occurring >3 months after the incident NV fracture (>6 months were required for fractures occurring at the same site as the incident fracture). The study assessed prevalence of subsequent fractures and compared costs (from the payer's perspective) between patients with and without subsequent fractures over the year following an incident NV fracture. RESULTS: Among privately insured NV fracture patients, 14.1% had any subsequent NV fractures, 1.6% had subsequent hip fractures, and 13.0% had subsequent non-vertebral, non-hip (NVNH) fractures, while 22.6% of Medicare NV fracture patients had subsequent NV fractures, 9.4% had subsequent hip fractures, and 15.5% had subsequent NVNH fractures. Mean excess health care costs per privately insured subsequent fracture patient were $9,789 ($19,072 vs. $9,914, p < 0.01), while excess medical costs per Medicare subsequent fracture patient were $12,527 ($31,904 vs. $19,377, p < 0.01). CONCLUSIONS: NV fracture patients are at substantial risk for subsequent NV fractures within 1 year, and patients who incur subsequent fractures are significantly more costly than those who do not during the year following an incident fracture.

Economic burden of privately insured non-vertebral fracture patients with osteoporosis over a 2-year period in the US.

UNLABELLED: This study assesses the costs of non-vertebral osteoporosis-related fractures patients compared with osteoporosis patients without fractures, focusing on the second year following a fracture. Since fracture patients remained more costly in the second year, their economic burden extends beyond the year in which the fracture occurs. INTRODUCTION: The purpose of this study is to examine the comorbidity profile, resource use, and direct costs of patients who incur osteoporosis-related non-vertebral (NV) fractures in the United States during the 2 years following an incident fracture, focusing on the second year following a fracture. METHODS: Osteoporosis patients (ICD-9-CM: 733.0) with a NV fracture (hip, femur, pelvis, lower leg, upper arm, forearm, rib, and multiple sites) were selected from a privately insured health insurance claims database (>8 million lives, ages 18-64, 1999-2006). These NV fracture patients were randomly matched 1:1 on age, gender, employment status, and geographic region to controls with osteoporosis but without a fracture history. Year-by-year and month-by-month rates of comorbidities, resource use, and direct costs were calculated for the matched sample (N = 3,781). RESULTS: Comorbidity rates and resource use remained significantly higher among NV fracture patients during second year following an NV fracture compared with controls, although absolute rates of comorbidities and service utilization declined. Mean direct excess costs for NV fracture patients fell from $5,267 in the first year to $2,072 in the second year after a fracture, but remained statistically significant (p < 0.01). Patients with fractures of the pelvis, hip, and femur had the highest excess costs in the second year ($5,121, $3,930, and $3,828, respectively). Although hip fractures had highest excess costs over both years, non-vertebral, non-hip fracture patients made up a larger proportion of the sample and were significantly more costly than controls. CONCLUSIONS: Patients with osteoporosis-related NV fractures have substantial excess costs beyond the first year in which the fracture occurs.

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.

Fracture Reduction Affects Medicare Economics (FRAME): impact of increased osteoporosis diagnosis and treatment.

Osteoporosis is a common, debilitating disease affecting US Medicare beneficiaries, yet diagnosis and treatment lag behind medical advances. We estimated the cost of fractures to the Medicare program and the impact of increasing osteoporosis diagnosis and treatment. A Markov model was used to predict fracture incidence and costs in postmenopausal women aged 65 years and older, over 3 years (2001-2003). Only 1.80 million women were estimated to receive a Medicare-reimbursed bone mineral density (BMD) test in 2001. We evaluated the budget impact of testing an additional 1 million women from Medicare and patient perspectives. These women were stratified into high-risk (osteoporotic with prevalent vertebral fracture) and moderate-risk (without prevalent vertebral fracture) groups. During 2001-2003, an estimated 2.39 million fractures occurred among the 5.11 million women aged 65+ with osteoporosis, at a cost to Medicare of 12.96 billion dollars. We projected that BMD testing of an additional 1 million women in 2001 would result in treatment of 440,000 new patients with a bone-specific medication, preventing over 35,000 fractures over the 3 years. The decrease in fractures would produce a net discounted savings to the Medicare budget of 77.86 million dollars. Medicare's hospital inpatient cost would decrease by 115.41 million dollars and long-term care cost by 43.51 million dollars, more than offsetting incremental outpatient cost of 81.07 million dollars. Patients would benefit from fracture avoidance, but their out-of-pocket medical costs would increase by 63.49 million dollars during 2001-2003, or 1,771 dollars per fracture avoided. Sensitivity analyses showed that savings to the Medicare program varied in proportion to the unit cost of fractures, fracture risk of the populations tested, treatment rate, and adherence to therapy. Increased osteoporosis diagnosis may produce savings for the Medicare program if interventions are targeted to women at elevated risk for fracture and may be budget neutral if all older women are screened.

One year outcomes and costs following a vertebral fracture.

Vertebral fractures are believed to be important predictors for future vertebral and other fractures, leading to at least a 4- to 5-fold increase in the risk of subsequent fractures. However, little is known about their associated near-term costs. The purpose of this study was to quantify the subsequent fracture and cost outcomes emanating from patients with an incident vertebral fracture. A probabilistic decision analysis model was developed to estimate the expected cost of all subsequent fractures. We ran Kaplan-Meier time-to-event models on placebo patients in risedronate's pivotal phase III clinical trial data to determine the cumulative incidence or probabilities of all fractures within one year of an incident vertebral fracture. Unit costs for health care payers in the USA and Sweden for vertebral, hip, other, and forearm/wrist fractures were multiplied by fracture probabilities to generate the expected costs of new fractures within one year of incident vertebral fractures. Our analysis found that that 26.1% of vertebral fracture patients with a mean age of 74 years refractured within 1 year (vertebral 17.4%; hip 3.6%; "other" 3.5%; forearm/wrist 1.6%). The calculated medical costs for those patients who refracture within 1 year was $5906 and 3670 euros for the USA and Sweden, respectively, while the weighted average cost across all patients (refracture and non-fracture) within a year of their incident fracture was $1541 (USA) and 958 euros (Sweden). These results suggest that therapies with proven, rapid efficacy may offer important economic value to healthcare payers, providers and patients.

Hospital care of osteoporosis-related vertebral fractures.

Resource implications of hospitalization for osteoporosis-related vertebral fracture are sparsely documented. This study utilized data abstracted from a national sample of hospitalized patients to identify characteristics of patients who are hospitalized with vertebral fracture and their patterns of resource utilization. These were compared with patterns observed for hip fracture hospitalizations. Data from the Nationwide Inpatient Sample (NIS) for 1997 were used to identify men and women age 45 years and above who had a primary diagnosis of vertebral fracture. After patients whose fractures might have been due to metastatic cancer or severe trauma were excluded, 68,901 individuals hospitalized for vertebral fracture were identified. Seventy-seven percent of these were women, most were white, 75 years and older, and had multiple comorbid diagnoses. Total charges averaged 8000-10,000 US dollars per hospitalization and were higher in men. Mean length of stay was just under 6 days and more than 50% of discharged patients required some form of continuing care. Hospitalizations for vertebral fracture occurred at only one-fourth the rate of those for hip fracture, and created only half the hospital charges per admission. Vertebral fracture accounted for over 400,000 total hospital days and generated charges in excess of 500 million US dollars. This resource impact is considerably higher than has been described in prior studies.

Resource-based relative-value scale expansion: implications for performance and quality of care.

OBJECTIVE: To assess the impact on the delivery of physician services from expanded use of Medicare's Resource-Based Relative-Value Scale (RBRVS) by multiple payers. DESIGN: A 1993 survey of insurers and targeted case studies of payers. RESULTS: Approximately one third of surveyed payers were using RBRVS in some fashion to pay for physician services, while another 40% were considering its adoption. The RBRVS is spreading to many types of payers--both public and private--and to health insurance product lines. Penetration of RBRVS is most prevalent within managed-care arrangements, accounting for 75% of all RBRVS-based products among payers. Many payers were found to be modifying aspects of the RBRVS and applying payment policies tailored to their specific needs. Most payers expect to achieve cost control, and several may be using RBRVS to profile physician service utilization. CONCLUSIONS: The diffusion or RBRVS to multiple payers may have a profound impact on the distribution of services provided, how these services are delivered, and the quality of care provided. Providers may respond to RBRVS by reducing some types of services, while increasing others, and using new resource combinations. Managed-care payers are likely to continue using RBRVS for negotiating fee schedules or for allocating payments for bundled service packages and capitation and sub-capitation products among physicians. As larger shares of physicians' incomes are driven by RBRVS, the underlying incentives become more critical. Nevertheless, RBRVS will remain an important payment approach in the future. The impact on quality and delivery of physician services from broader use of RBRVS cannot be measured adequately until future empirical studies are undertaken.

Diffusion of Medicare's RBRVS and related physician payment policies.

In 1992, Medicare reformed its physician payment method by implementing the Medicare fee schedule (MFS), of which the resource-based relative value scale (RBRVS) is a major component. Using a recent survey and case studies, we examine the diffusion of Medicare's RBRVS to non-Medicare payers and how those payers use and perceive the RBRVS and MFS policies. We find that approximately one-third of payers that participated in the survey have adopted RBRVS-based payment systems in varying degrees while another 40 percent were seriously considering its adoption. Prospects for expanded use of Medicare's RBRVS appear favorable.

Allocating practice expense under the Medicare fee schedule.

Currently, relative value units for practice expense are determined under the Medicare fee schedule (MFS) using historical physician charges. This seems inconsistent with the goal of a resource-based fee schedule. A specialty resource-based method of determining practice expense payments is presented and simulated here. The method assumes that, for each service, the payment for practice expense should be the same proportion of the total payment as actual physician practice expenses are of total practice revenues. A comparison with the approach developed by the Physician Payment Review Commission (PPRC) shows similar fees, but the specialty-based method proposed here requires no data beyond what is already employed in the MFS.

Inefficiencies in physician practices.

Explosive growth in spending on physician services in the 1980s has focussed the attention of policymakers and researchers on inefficiencies in physician practices. This chapter surveys the recent literature on inefficiencies in physician practices and provides a review, critique, and synthesis of empirical findings. The major emphasis is on measurement and estimates of economies of scale in physician practices. The paper concludes with a discussion of limitations of current knowledge and methods, and directions for future research.