Advancing a managed care pharmacy research agenda: Generating real-world evidence to support US Food and Drug Administration Accelerated Approvals and improving benefit design to address health inequities.

To advance their research agenda, the Academy of Managed Care Pharmacy (AMCP) and the AMCP Foundation (AMCPF) invited a sample of AMCP membership to participate in focus groups and tasked them with developing tangible research aims for each of the top 2 previously identified AMCP/AMCPF research priorities: generating real-world evidence (RWE) to support US Food and Drug Administration (FDA) Accelerated Approvals and improving benefit design to address health inequities. The resulting research aims, which were further refined per feedback from additional stakeholders, will serve to guide requests for proposals for funding of specific research projects to address these top managed care priorities. Research aims identified by focus group participants related to generating RWE for FDA Accelerated Approvals include (1) creating a data survey tool for managed care to make RWE more readily available, (2) linking surrogate endpoints to meaningful clinical outcomes for drug development, and (3) improving patient outcomes by determining the optimal sequence of clinical pathways. Research aims identified by focus group participants related to improving benefit design to address health inequities include (1) identifying how the ability to navigate managed care benefit designs may impact inequities, (2) understanding the connection between health inequities and medication adherence, and (3) evaluating the impact of social determinants of health on medication affordability. DISCLOSURES: These proceedings were supported by Bridget Flavin, PharmD, Founder, Connected Content, Ltd. Connected Content, Ltd. received payment from AMCP for the preparation of this manuscript. Flavin is also an adjunct associate professor at the University of Florida College of Pharmacy. Diana Brixner received AMCP Foundation support of sabbatical to conduct this work, support of a medical writer to assist in putting the manuscript together, consulting fees from Millcreek Outcomes Group, Elevar, Sage, Haymarket, and AMCP funding of one trip to Alexandria, VA. This research and the development of this manuscript were funded by AMCP and the AMCP Foundation.

Value-based care through postacute home health under CMS PACT regulations.

OBJECTIVES: To assess in a Medicare Advantage population (1) whether discharge to home health, compared with discharge to home, following an inpatient stay subject to CMS postacute care transfer (PACT) regulations, is associated with better outcomes or lower expenditures and (2) whether the impact differs among subpopulations. STUDY DESIGN: Claims-based retrospective cohort study. METHODS: Instrumental variable (IV) analysis, with prior hospital-level probability of discharge to home health as the IV, to control for unobservable as well as observable confounders. RESULTS: Compared with 15,071 patients discharged to home, 4160 patients discharged to and receiving timely home health services were 60% less likely to be readmitted within 30 days and 37% less likely at 90 days. Total expenditures from time of admission to 90 days post discharge were 11% lower in the home health group. The association of discharge to home health with reduced readmission and reduced costs varied by subpopulations defined by surgical vs medical diagnosis-related group and receipt of intensive care management following discharge. CONCLUSIONS: The PACT policy may be promoting greater value by reducing readmissions while lowering total expenditures for patients who do not require intensive postacute care. Findings were in contrast to those of previous studies, in which discharge to home health has been associated with higher rates of readmission. Earlier studies did not control for unmeasurable confounders, involved narrowly defined populations, and used older data.

A Retrospective Database Study Comparing Diabetes-Related Medication Adherence and Health Outcomes for Mail-Order Versus Community Pharmacy.

BACKGROUND: Adherence to oral antihyperglycemic agents (AHAs) is important for managing blood glucose levels and avoiding hospitalizations or diabetes complications. Previous studies have found that use of mail-order pharmacy dispensing channels results in greater adherence than use of community pharmacies, but the link between use of mail-order pharmacies and improved clinical outcomes has not been established. OBJECTIVE: To compare the effect of mail-order and community pharmacy use on adherence to oral AHAs, hemoglobin A1c (A1c) level, and glycemic control, as well as emergency department (ED) and inpatient hospital use. METHODS: This retrospective cohort study of administrative claims data from January 1, 2008, to December 31, 2016, included patients with Medicare Advantage Prescription Drug plan coverage with ≥ 2 claims for the same oral AHA and a diagnosis of type 2 diabetes mellitus (T2DM). Patients were indexed to the start of the most advanced oral AHA identified to begin study observations at the start of a new treatment and assigned to mail-order or community pharmacy cohorts based on which channel dispensed ≥ 80% of their oral AHA claims; all others were excluded. Mail-order and community pharmacy patients were 1:1 propensity score matched. Matched cohorts were compared on proportion of days covered (PDC), adherence (PDC ≥ 0.8), A1c level, glycemic control, and ED and inpatient use for measurement periods of 12, 24, 36, and 48 months post-index. RESULTS: 19,307 mail-order and 19,307 community pharmacy users were matched. PDC was higher for mail-order pharmacy users at 12 months (0.93 vs. 0.82, P < 0.001) and sustainable through 48 months (0.87 vs. 0.77, P < 0.001). Adherence was also greater for mail-order pharmacy patients through 12 months (86% vs. 68%, P < 0.001) and sustainable through 48 months (78% vs. 62%, P < 0.001). Glycemic control as A1c < 7% was not significantly different, but control as A1c < 8% was greater for mail-order pharmacy users at 12 months (91% vs. 89%, P = 0.006) and was greater through 36 months (93% vs. 89%, P = 0.043). Effects on A1c level were not evident. Mail-order pharmacy users were less likely to have an ED visit within 12 months (26% vs. 28%, P < 0.0001), and the difference was observed through 36 months (50% vs. 54%, P < 0.0001). Similarly, fewer mail-order pharmacy users had an inpatient hospitalization within 12 months (17% vs. 19%, P < 0.0001), and the difference was observed through 48 months (43% vs. 47%, P = 0.009). CONCLUSIONS: The results of the study demonstrate a benefit to patients who use mail-order pharmacies for chronic medications to treat T2DM. The study identified greater glycemic control, lower ED use, and lower hospitalization among individuals using mail-order pharmacies. These positive outcomes were evident in the near term and sustained over time. DISCLOSURES: This study received no outside funding but was sponsored by Humana through regular employment activities by Schwab, Racsa, and Worley, who are employed by Humana Healthcare Research (formerly Comprehensive Health Insights). This study found benefits related to using mail-order versus community pharmacies for dispensing antihyperglycemic agents in the treatment of type 2 diabetes. Humana owns mail-order pharmacies under the Humana Pharmacy subsidiary. Mourer and Meah are paid employees of Humana Pharmacy Solutions. Rascati is employed by the University of Texas College of Pharmacy at Austin.

Retrospective analysis of outcomes following inferior vena cava (IVC) filter placement in a managed care population.

The role of inferior vena cava filter (IVC) filters for prevention of pulmonary embolism (PE) is controversial. This study evaluated outcomes of IVC filter placement in a managed care population. This retrospective cohort study evaluated data for individuals with Humana healthcare coverage 2013-2014. The study population included 435 recipients of prophylactic IVC filters, 4376 recipients of therapeutic filters, and two control groups, each matched to filter recipients. Patients were followed for up to 2 years. Post-index anticoagulant use, mortality, filter removal, device-related complications, and all-cause utilization. Adjusted regression analyses showed a positive association between filter placement and anticoagulant use at 3 months: odds ratio (ORs) 3.403 (95% CI 1.912-6.059), prophylactic; OR, 1.356 (95% CI 1.164-1.58), therapeutic. Filters were removed in 15.67% of prophylactic and 5.69% of therapeutic filter cases. Complication rates were higher with prophylactic procedures than with therapeutic procedures and typically exceeded 2% in the prophylactic group. Each form of filter placement was associated with increases in all-cause hospitalization (regression coefficient 0.295 [95% CI 0.093-0.498], prophylactic; 0.673 [95% CI 0.547-0.798], therapeutic) and readmissions (OR 2.444 [95% CI 1.298-4.602], prophylactic; 2.074 [95% CI 1.644-2.616], therapeutic). IVC filter placement in this managed care population was associated with increased use of anticoagulants and greater healthcare utilization compared to controls, low rates of retrieval, and notable rates of device-related complications, with effects especially pronounced in assessments of prophylactic filters. These findings underscore the need for appropriate use of IVC filters.

Adherence, Persistence, and Health Care Costs for Patients Receiving Dipeptidyl Peptidase-4 Inhibitors.

BACKGROUND: The dipeptidyl peptidase-4 (DPP-4) inhibitors are among the newer, yet more established, classes of diabetes medications. OBJECTIVE: To compare adherence, persistence, and health care costs among patients taking DPP-4 inhibitors. METHODS: Claims were extracted from Humana Medicare Advantage Prescription Drug (MAPD) or commercial plans for patients aged > 18 years with ≥ 1 prescription filled for a DPP-4 inhibitor between July 1, 2011, and March 31, 2013. The first prescription claim for a DPP-4 inhibitor established the index date and index medication; 12-month pre-index and post-index data were analyzed. The Diabetes Complications Severity Index (DCSI) was used to assess a level of baseline diabetes-related comorbidities. Adherence (proportion of days covered [PDC] ≥ 80%) and persistence (< 31-day gap) measures were compared before and after, adjusting for DCSI, pre-index insulin, age, and gender. Post-index costs (in 2013 U.S. dollars) were compared using general linear modeling (GLM) to adjust for pre-index costs, DCSI, pre-index insulin, age, and gender. RESULTS: Based on study criteria, 22,860 patients with MAPD coverage (17,292 sitagliptin, 4,282 saxagliptin, and 1,286 linagliptin) and 3,229 patients with commercial coverage (2,368 sitagliptin, 643 saxagliptin, and 218 linagliptin) were included. For MAPD patients, the mean age was 70-72 years, and females represented 50%-52% of patients. For commercial patients, mean age was 55-56 years, and females represented 44% of patients. Clinical indicators for patients on linagliptin showed a higher comorbidity level than sitagliptin or saxagliptin cohorts (MAPD DCSI 3.0 vs 2.4 and 2.2, P < 0.001; commercial DCSI 1.2 vs. 0.9 and 0.9, P < 0.001); a higher use of pre-index insulin (MAPD 22% vs. 15% and 14%, P < 0.001; commercial 18% vs. 11% and 10%, P = 0.003); and higher mean pre-index costs (MAPD $14,448 vs. $11,818 and $10,399, P < 0.001; commercial $13,868 vs. $9,357 and $8,223, P = 0.016). For the MAPD cohort, the unadjusted PDC was lower for linagliptin patients (67%) compared with saxagliptin (72%) or sitagliptin (72%) patients (P < 0.001). Significant differences were still seen when adjusted for covariates. Linagliptin patients were more likely to be nonpersistent (73%) than those on saxagliptin (65%) or sitagliptin (67%; P < 0.01 for adjusted and unadjusted comparisons). For the commercial population, there were no significant differences in mean PDC between the 3 groups (linagliptin 70%, saxagliptin 72%, and sitagliptin 74%; P = 0.096). Dichotomized comparisons of nonpersistence were significantly different (linagliptin 65%, saxagliptin 62%, and sitagliptin 57%; P = 0.010), although upon adjustment using a Cox proportional hazard model, no significant differences were found. When controlling for other factors, post-index adjusted health care costs were similar between the medication cohorts (MAPD: sitagliptin = $13,913, saxagliptin = $13,651, and linagliptin = $13,859; commercial: sitagliptin = $11,677, saxagliptin = $12,059, and linagliptin = $11,163; all P > 0.25). CONCLUSIONS: For MAPD and commercial populations, baseline patient demographics were similar between the 3 DPP-4 inhibitor groups, but the linagliptin group may have had more complex patients (higher pre-index costs, higher DCSI, and more use of insulin). For the MAPD population, patients on linagliptin were less adherent and persistent than patients taking sitagliptin or saxagliptin for all unadjusted and adjusted comparisons. For the commercial population, which was notably smaller, these differences were in the same direction, but not all were statistically significant. When controlling for baseline factors, 12-month post-index direct medical health care costs were similar between index DPP-4 inhibitors. DISCLOSURES: No external funding was provided for this research. The project was done as part of internal work by Humana employees. Rascati received no compensation. None of the authors have any financial disclosures or conflicts of interests to report. Worley and Everhart are employees of Comprehensive Health Insights, a subsidiary of Humana, and Meah is an employee of Humana. Discussion of the adherence and persistence data was presented as a poster at the Academy of Managed Care Pharmacy Nexus Conference, October 2015. Cost data were presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research 18th Annual European Congress, November 2015. Study concept and design were contributed by Rascati, Worley, and Meah, along with Everhart. Rascati took the lead in data collection, assisted by Meah, and data interpretation was performed by all the authors. The manuscript was written primarily by Rascati, along with Worley, Everhart, and Meah, and revised by Rascati, Everhart, and Worley, with assistance from Meah.

Does Hepatitis C Treatment Adherence Affect Risk of Liver Transplantation? A Historical Cohort Study.

BACKGROUND: Chronic hepatitis C virus (HCV) is the primary cause of liver failure leading to transplantation, and medication adherence is essential to the therapeutic efficacy of HCV treatments. While there is evidence linking poor adherence with increased utilization and cost, published literature lacks examination of the association between medication adherence and risk of liver transplant. In addition, the impact of HCV treatment on total costs of liver transplantation is not well documented. OBJECTIVES: To compare (a) the relative risk of liver transplant by adherence in patients treated for HCV and (b) the total health care costs in treated and untreated patients who require liver transplant. METHODS: This observational, historical cohort study was conducted using administrative data from the Humana Research Database. To be included, patients were required to have a documented HCV diagnosis or treatment between January 1, 2008, and June 30, 2013. Patients were excluded if they had a hepatitis B diagnosis, were not fully insured by a commercial or Medicare Advantage Prescription Drug plan, or were outside the age range of 19-89 years. No minimum pre- or post-index enrollment period was required, and patients were followed for their entire post-index enrollment through December 31, 2013. The study population was divided into treated and untreated groups and then subdivided by presence or absence of a liver transplant. Date of liver transplant was defined as the index date for untreated liver transplant patients; otherwise, the index date was defined as either the date of first observed HCV treatment or diagnosis date (if no treatment or liver transplant). Cox proportional hazards models were used to estimate the relative risk of liver transplant by level of treatment adherence (> 80%, 50%-79%, and < 50%) based on proportion of days covered. General linearized models with log link and gamma distribution were used to compare median total health care costs from index date until end of study period (or death/disenrollment, whichever came first) between treated and untreated liver transplant patients. All costs were converted to 2013 U.S. dollars and reported as total costs per patient and per patient per month (PPPM) to account for varying follow-up periods. RESULTS: Of the 53,423 patients identified with HCV, 10,377 met exclusion criteria, leaving 43,046 patients (primarily Caucasian, males, mean age of 58 years) in the initial cohort. Only 6.29% (n = 2,708) of the total HCV cohort received HCV treatment, and less than 1% (n = 366, 0.8%) received a liver transplant. Although there were no significant differences in the risk of liver transplant by adherence level, there was an upwards trend in the rate of liver transplant as adherence worsened (> 80%: 1.25%; 50%-79%: 1.30%; and < 50%: 1.99%), and the average days to liver transplant was longer with higher adherence (> 80%: 683; 50%-79%: 623; < 50%: 454). Only 48 (13.11%) patients who received a liver transplant were treated for HCV. Adjusted median total and PPPM health care costs measured from index date until end of the study period were significantly higher for patients who received HCV treatment compared with those who did not (total=$231,139 vs. $86,167, adjusted P < 0.001; PPPM=$20,583 vs. $5,778, adjusted P = 0.008), driven by HCV-related medical costs and total pharmacy costs. CONCLUSIONS: Adherence with HCV regimens did not affect risk of liver transplant, underscoring the need for further evidence linking treatment adherence to future liver transplant risk. HCV-treated patients who required liver transplant incurred significantly higher health care costs than those without HCV treatment before liver transplant. Introduction of newer all-oral direct-acting antiviral regimens, with higher acquisition costs, will require further research to more accurately assess medication adherence and its relationship with transplantation, as well as with total health care costs. DISCLOSURES: No outside funding supported this research. Ems, Worley, Racsa, Gregory, Anderson, and Holt are employees of Humana. Brill has participated in a physician advisory board at Humana. The authors have no other financial disclosures to report. Study concept and design were contributed by Ems, Racsa, Worley, and Anderson, along with Gregory, Brill, and Holt. Racsa took the lead in data collection, along with Ems and Worley. All authors participated in data interpretation. Anderson, along with the other authors, wrote the manuscript, which was revised by Brill and Holt, with assistance from the other authors.

Comparing two tyrosine kinase inhibitors for treatment of advanced renal cell carcinoma in Medicare and commercially insured patients.

OBJECTIVE: The objective of this study was to compare treatment characteristics, survival and costs for sunitinib and pazopanib for advanced renal cell carcinoma (RCC) in a real-world setting. METHODS: Using claims data, this observational, retrospective cohort study selected individuals aged 19 to 89 years, with commercial or Medicare insurance, advanced RCC, and at least one pharmacy claim for sunitinib or pazopanib between 1 November 2009 and 31 December 2012. Treatment characteristics (treatment interruption, adherence, duration and discontinuation), survival, and costs were measured up to 12 months. Statistical models were adjusted for age, gender, geographic region, race, and RxRisk-V score. RESULTS: At baseline, pazopanib patients exhibited significantly worse health status indicators (RxRisk-V score, number of pharmacy claims, and pre-index total healthcare costs) than sunitinib patients. There were no differences in treatment characteristics or survival. Index medication costs (mean difference $5580, p = 0.03, adj p = 0.05) and total healthcare costs (mean difference $12,192, p = 0.09, adj p = 0.07) trended higher with sunitinib. Patients non-adherent with sunitinib incurred significantly higher total costs compared to patients non-adherent with pazopanib (mean difference $17,680, p = 0.04, adj p = 0.01). CONCLUSIONS: Mortality data and proxy variables for treatment effectiveness indicate comparable clinical value for both medications. Sunitinib treatment trended towards higher index medication and total healthcare costs despite higher pre-index total costs and worse health status indicators at baseline with pazopanib. Non-adherence with sunitinib was associated with significantly higher total healthcare costs, which may indicate differences in tolerability between the two agents and requires further investigation.

Retrospective database analysis of the impact of prior authorization for type 2 diabetes medications on health care costs in a Medicare Advantage Prescription Drug Plan population.

BACKGROUND: Health plans and pharmacy benefit managers have implemented utilization management strategies for newer type 2 diabetes mellitus (T2DM) medications to control pharmacy expenditures. Little is known about the impact of utilization management strategies on overall health care costs and subsequent use of T2DM medications among members who request, but do not receive, a T2DM medication requiring prior authorization (PA).  OBJECTIVE: To examine the relationship between the receipt of a T2DM medication requiring PA, health care costs, and subsequent treatment for T2DM.  METHODS: A retrospective cohort study using pharmacy, medical, and laboratory claims data was conducted among Medicare Advantage Prescription Drug plan members with a denied claim for a T2DM medication requiring PA (sitagliptin, a dipeptidyl peptidase-4 inhibitor [DPP-4i], and exenatide, an incretin mimetic) between January 1, 2008, and June 30, 2009. Subjects were required to have 12 months of continuous enrollment both before and after the index date. The entire study period was 24 months in duration, including a 12-month pre-index and 12-month post-index period. Three cohorts were identified: 1 that received a medication requiring PA (denied claim, subsequent fill) and 2 nonfilling control groups. Both control groups requested a medication requiring PA, as evidenced by the denied claim, but neither received the medication, either because the medication was not authorized or the member chose not to fill. Claims-based estimates were used to infer whether the individual likely met the criteria for PA, with 1 control group designated as having met the claims-based criteria (qualifying nonfilling cohort) and the other not having done so (nonqualifying nonfilling cohort.) The primary endpoint evaluated was the relationship between PA medication fill status and plan-paid costs (medical [including laboratory] and pharmacy) over the 12-month post-denial period, with generalized linear models adjusting for key covariates including demographics, concomitant medications, pre-index costs, pre-index adherence, and comorbidities. The secondary endpoint of T2DM medication use (post-denial) among the 2 nonfilling control groups was also evaluated.  RESULTS: There were 1,728 members identified who received medication for T2DM requiring PA (the received authorization cohort) and 2,373 who did not (606 qualifying nonfilling cohort; 1,767 nonqualifying nonfilling cohort.) Cohorts were similar with regard to age and gender, but the nonfilling cohort had more comorbidities. Total unadjusted plan-paid 12-month costs were lowest among the received authorization cohort ($11,739), slightly higher ($11,980) for the qualifying nonfilling cohort, and notably higher for the nonqualifying nonfilling cohort ($12,962), although no differences were statistically significant. After adjusting for key covariates, the difference between the nonqualifying nonfilling cohort ($11,980) and the received authorization cohort ($11,729) was statistically significant (P = 0.034). Large differences in plan-paid medical costs ($10,127 for the nonqualifying nonfilling cohort vs. $8,192 for the received authorization cohort) appeared to drive the overall cost totals and were significant in both the unadjusted (P = 0.005) and adjusted models (P less than 0.001). Pharmacy costs were significantly lower for the nonqualifying nonfilling cohort in the adjusted model and for the qualifying nonfilling cohort in both models (all P less than 0.001), but the lower pharmacy costs were not offset by the higher medical costs. In examining the use of medication for treatment of T2DM following the denied claim, 10.6% of the qualifying nonfilling cohort and 13.4% of the nonqualifying nonfilling cohort added another oral therapy, 10.2% and 5.8% added insulin, and 11.9% and 7.1% had treatment intensification, respectively. More than half (56.1%) of the qualifying nonfilling cohort, but only 32.1% of the nonqualifying nonfilling cohort, maintained current therapy.   CONCLUSIONS: This study found higher plan-paid health care costs (overall and medical alone) among members who requested a type 2 diabetes medication requiring PA, but never received it, compared with those who qualified for and received the requested medication. A notable number of individuals who were assumed to have met the criteria based on a claims-based equivalent, but who never received the medication, made no change to their current therapy. Failure of a member to take medication deemed necessary by his or her physician could translate to inadequate control of the diabetic condition and result in an excess of resource utilization and costs for treating the disease and associated comorbidities. In light of the present findings, health plans should consider not only the impact of utilization management strategies on reducing pharmacy costs, but the broader implication for overall health care costs and subsequent treatment patterns among members. 

Comparison of risedronate to alendronate and calcitonin for early reduction of nonvertebral fracture risk: results from a managed care administrative claims database.

OBJECTIVE: Recent randomized clinical trials have shown that risedronate reduces the risk of nonvertebral fractures and clinical vertebral fractures within 6 months of initiating treatment. The objective of the current study was to determine whether this early antifracture effect could be demonstrated in nonvertebral fractures for risedronate and other osteoporosis therapies in an observational administrative claims database. METHODS: A proprietary administrative claims database was used to identify managed care members who received a new prescription for risedronate, alendronate, or nasal calcitonin from July 1, 2000, to December 31, 2001. Patient records were analyzed for the incidence of nonvertebral fractures (clavicle, humerus, wrist, pelvis, hip, and leg) in the first 6 and 12 months following initiation of treatment. A Cox proportional hazards regression model was used to estimate relative risk (RR) of fracture at 6 and 12 months. RESULTS: In the 6-month analysis, 774 patients (11%) received calcitonin, 5,307 (75%) received alendronate, and 1,000 (14%) received risedronate. Twelve-month data were available for a subset (71%) of patients (656 calcitonin [13%], 3,716 alendronate [74%], and 652 risedronate [13%]). Most were women (93%); mean age was similar for alendronate and risedronate, and nasal calcitonin patients were about 3 years older, on average. Risedronate and alendronate patients were more likely to have used estrogen, while nasal calcitonin patients were more likely to have been hospitalized and had higher use of concomitant medications and more physician visits. Relative risks were adjusted for these differences. Risedronate and alendronate patients were similar with respect to these indicators of general health status. In the 6-month analysis, nonvertebral fractures were observed in 2.2% of patients receiving nasal calcitonin, 1.4% of patients receiving alendronate, and 0.6% of patients receiving risedronate. The adjusted RR reduction was 69% for risedronate versus calcitonin (RR = 0.31; 95% CI, 0.12 to 0.81; P = 0.02), 54% for risedronate versus alendronate (RR = 0.46; 95% CI, 0.20 to 1.06; P = 0.07), and 26% for alendronate versus calcitonin (RR = 0.74; 95% CI, 0.43 to 1.27; P = 0.28). In the 12-month analysis, nonvertebral fracture rates were 2.9% for nasal calcitonin, 2.4% for alendronate, and 0.9% for risedronate patients. The adjusted RR reduction was 75% for risedronate versus calcitonin (RR = 0.25; 95% CI, 0.10 to 0.64; P<0.01), 59% for risedronate versus alendronate (RR = 0.41; 95% CI, 0.18 to 0.94; P = 0.04), and 25% for alendronate versus calcitonin (RR = 0.75; 95% CI, 0.45 to 1.25; P = 0.27). CONCLUSIONS: This analysis of medical and pharmacy claims contained in an administrative database confirms the early fracture reduction with risedronate that was shown in randomized clinical trials. Risedronate was more effective than calcitonin in reducing the risk of nonvertebral fractures within the first 6 months of treatment. Risedronate was more effective than either calcitonin or alendronate in reducing the risk of nonvertebral fractures within 12 months of treatment.