Does the offer of free prescriptions increase generic prescribing?

OBJECTIVES: To test if offering zero generic co-pays for oral antidiabetic drugs (OADs) and statins increases generic dispensing for low-income subsidy (LIS) recipients with diabetes enrolled in Medicare Part D. STUDY DESIGN: We analyzed a natural experiment in which LIS recipients were randomized to Part D plans in 2008. Some plans placed selected generic OADs and statins on zero co-pay tiers whereas others did not. Randomization eliminated selection effects which could bias the study findings. METHODS: We analyzed a 5% random sample of Medicare beneficiaries with diabetes from the Chronic Condition Data Warehouse using Part D claims, formulary provisions, and co-pay tiers together with a special file prepared by CMS that identified all randomly assigned LIS recipients in 2008. We calculated proportions using generic drugs in the 2 classes and annual days' supply among users in plans with and without zero co-pay tiers for the country as a whole and California (where zero co-pay plans were particularly popular). RESULTS: We found that the demand for generic OADs was not significantly different in plans with and without zero co-pay tiers. By contrast, a large difference was observed in the percent of LIS recipients using generic statins in plans with zero co-pay tiers (61.4% vs 54.6%; P <.01). However, the difference disappeared once we controlled for formulary restrictions on the most popular brand statin at the time (Lipitor). CONCLUSIONS: This cautionary tale suggests that policy makers should give greater consideration to formulary provisions when evaluating the effects of free generics in value-based insurance designs.

How Low-Income Subsidy Recipients Respond to Medicare Part D Cost Sharing.

OBJECTIVES: To determine the magnitude and mechanisms of response to Medicare Part D cost sharing by low-income subsidy (LIS) recipients using oral hypoglycemic agents (OHAs) and statins. DATA SOURCES: Medicare data for a 5 percent random sample of beneficiaries with diabetes enrolled in fee-for-service Part D drug plans in 2008. STUDY DESIGN: We evaluated the impact of differences between generic and brand cost sharing rates among cohorts of LIS and non-LIS recipients to determine if wider price spreads increased the generic dispensing rate (GDR) and reduced total drug use and cost. PRINCIPAL FINDINGS: We found little association between cost sharing and aggregate OHA and statin use. In adjusted analyses, non-LIS beneficiaries who paid 46 percent of total OHA costs had 2.5 percent fewer OHA days supply than full benefit dual eligibles who paid just 5 percent of their therapy costs. For statins, the difference in days supply between those facing the lowest and highest cost sharing was 4.6 percent. Higher cost sharing was associated with filling fewer but larger prescriptions for both generics and brands. CONCLUSIONS: Higher generic and brand copays had little association with OHA and statin use among LIS recipients. This implies that modest changes in required cost sharing for these medicines would have very little substantive impact on generic dispensing or utilization patterns among LIS recipients and thus would have little effect on total program spending. At the same time, any increases in out-of-pocket costs would be expected to shift costs and place greater financial burden on low-income beneficiaries, particularly those in poor health.

Eligibility For And Enrollment In Medicare Part D Medication Therapy Management Programs Varies By Plan Sponsor.

Medicare Part D prescription drug plans must offer medication therapy management to beneficiaries with multiple chronic conditions and high drug expenditures. However, plan sponsors have considerable latitude in setting eligibility criteria. Newly available data indicate that enrollment rates in medication therapy management among stand-alone prescription drug plans and Medicare Advantage drug plans averaged only 10 percent in 2012. The enrollment variation across plan sponsors-from less than 0.2 percent to more than 57.0 percent-was associated with the restrictiveness of their eligibility criteria. For example, enrollment was 16.4 percent in plans requiring two chronic conditions versus 9.2 percent in plans requiring three, and 12.7 percent in plans requiring the use of any Part D drug versus 4.4 percent in plans requiring the use of drugs in specific classes. This variation represents inequities in access to medication therapy management across plans and results in missed opportunities for interventions that might improve therapeutic outcomes and reduce spending. The new Part D Enhanced Medication Therapy Management model of the Centers for Medicare and Medicaid Services has the potential to significantly increase the impact of medication therapy management by aligning financial incentives with improvements in medication use and encouraging innovation.

Proximal Predictors of Long-Term Discontinuance with Noninsulin Antihyperglycemic Agents.

BACKGROUND: Noninsulin antihyperglycemic agents (NAAs) are the mainstay of treatment for type 2 diabetes, yet persistence in NAA use is suboptimal in many diabetes patients. Most of the research on NAA discontinuance has focused on sociodemographic characteristics and general health status, but such factors are inherently limited in explaining dynamic events such as discontinuance. OBJECTIVE: To assess the relative importance of static and proximal dynamic factors in explaining long-term NAA discontinuance among Medicare beneficiaries with diabetes. METHODS: Two sets of probability models were estimated to predict NAA discontinuance as a function of static variables (age, sex, race, original reason for Medicare entitlement, low-income subsidy and dual Medicare/Medicaid eligibility status, and disease burden) and 21 dynamic factors capturing month-by-month changes in drug use, health status, and use of medical services leading up to discontinuance (defined as month 0) and the previous 4 months (designated months -1 to -4) among 71,619 patients with diabetes enrolled in Medicare Part D plans in 2006-2008. RESULTS: Static variables explained just 1.2% of the variance in probability of NAA discontinuance compared with 14% for all variables combined. Key time-related predictors of NAA discontinuance included discontinuation with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) and statins, hypoglycemia, NAA usage gaps, insulin use, and discharge from hospitals and skilled nursing facilities (SNFs). The strongest significant predictors (P < 0.05) of NAA discontinuance were discontinuation with statins and ACEIs/ARBs in month 0 (predicted probabilities of 37% and 34%, respectively). Other variables that significantly increased the probability of NAA discontinuance by 10% or more were hypoglycemia in month 0 (14%) and month -1 (17%), discontinuance with ACEIs/ARBs in months -1 (15%) and -2 (10%), discontinuance with statins in month -1 (13%), and insulin use in month 0 (12%). Experiencing a previous gap in NAA therapy was associated with higher likelihood of discontinuance if the gap occurred in month -2 (10%) or month -4 (6%), but a gap in therapy in month -1 actually reduced the likelihood of discontinuance by 13%. Discharge from a hospital or SNF was consistently associated with higher probabilities of NAA discontinuance ranging between 4% and 10%, with higher probabilities occurring closer to month 0. CONCLUSIONS: A cascade of dynamic changes preceding discontinuance with NAA therapy among Medicare Part D enrollees with diabetes was observed between 2006 and 2008. Understanding that lack of persistence in drug use is a dynamic rather than a static phenomenon opens up new avenues for investigating and ultimately improving adherence behavior in the elderly. DISCLOSURES: This study was funded by Merck & Co. Huang and Raipathak are employees of Merck & Co. Brandt reports consultancy and speaker fees from Catapult, Omnicare, RAND, HRSA, CMS, and AGS Beers Criteria. Loh is currently employed at Touro College of Pharmacy. All other authors have no relevant potential conflicts of interest to disclose. Study concept and design were primarily contributed by Stuart, Quinn, and Brandt, along with Shen, Roberto, Hendrick, Huang, and Rajpathak. Shen, Loh, Hendrick, and Kim collected the data, and data interpretation was performed primarily by Stuart, Shen, and Roberto, assisted by Quinn, Brandt, Hendrick, Huang, and Rajpathak. The manuscript was written primarily by Stuart, with assistance from the other authors, and revised by Huang, Rajpathak, and Stuart, with assistance from the other authors.

Data, Data Everywhere, but Access Remains a Big Issue for Researchers: A Review of Access Policies for Publicly-Funded Patient-Level Health Care Data in the United States.

INTRODUCTION: High quality research regarding treatment effectiveness, quality, and value is critical for improving the U.S. health care system. Recognition of this has led federal and state officials to better leverage existing data sources such as medical claims and survey data, but access must be balanced with privacy concerns. METHODS: We reviewed and catalogued data access policies for a selection of publicly-funded federal and state datasets to investigate how such policies may be promoting or limiting research activities. RESULTS: We found significant variation in data access policies across federal agencies and across state agencies, including variation for multiple datasets available from the same agency. We also observed numerous indirect hurdles to use of data, including complex data use application procedures, high user fees, and prolonged wait times for data delivery. CONCLUSIONS: Policy makers and data owners should consider making changes to data access policies to maximize the utility and availability of these valuable resources.

Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes.

AIMS: Iron overload adversely affects patients with myelodysplastic syndromes (MDS), but benefits of iron chelation therapy have not been clearly demonstrated. We examined the association between deferasirox (DFX) therapy and mortality in transfusion-receiving Medicare patients. PATIENTS & METHODS: MDS patients from 2005 to 2008 were identified using ICD-9 codes from 100% Medicare claims. Patients receiving ≥20 blood units were observed until death or end of study. Marginal structural models were used for estimation. RESULTS: 3926 patients (10.1% used DFX) were observed for a mean of 48.8 weeks. Each incremental week of DFX was associated with a significant reduction in mortality risk (hazard ratio [HR]: 0.989; 95% CI: 0.983-0.996; p = 0.001). CONCLUSION: DFX therapy is associated with a reduced mortality risk among older MDS patients who received a minimum transfusion threshold.

Variations in erythropoiesis-stimulating agent administration in transfusion-dependent myelodysplastic syndromes impact response.

INTRODUCTION: Erythropoiesis-stimulating agents (ESAs) reduce red blood cell (RBC) transfusions in approximately 40% of patients with myelodysplastic syndrome (MDS) in clinical trials. We studied the association of timing of ESA initiation, agent (epoetin alfa, darbepoetin) and number of weeks of ESA use with response in MDS patients in routine practice. METHODS: Patients diagnosed with MDS from 2001 to 2005 were identified in the Surveillance Epidemiology and End Results-Medicare linked database. The study cohort consisted of patients with new-onset transfusion dependence (TD). All patients received an ESA at least once during the study period, which began the week that criteria for TD were met and continued until transfusion independence (TI). Kaplan-Meier statistics and Cox Proportional Hazard models were used to assess relationships between time to ESA initiation, agent and number of weeks of ESA use and TI attainment. RESULTS: Of 610 TD patients treated with ESAs, 210 (34.4%) achieved TI. Median time from ESA initiation to TI was 13 weeks. Shorter time from TD to ESA initiation and use of darbepoetin were associated with higher probability of achieving TI. The probability of achieving TI decreased beyond 8 weeks of treatment, and was very low beyond 16 weeks (8-15 weeks: HR=0.64, 16-31 weeks: HR=0.25, 32+ weeks HR=0.10). CONCLUSIONS: In this observational, population-based study, variations in ESA administration impacted response in transfusion-dependent MDS patients, with higher response rates with early administration and use of darbepoetin, and low response likelihood in non-responders beyond 16 weeks of therapy.

Patient cost sharing and receipt of erythropoiesis-stimulating agents through medicare part D.

PURPOSE: Medicare Part D prescription benefits cover injected medications, normally covered under Part B, when administered outside of physician offices. Erythropoiesis-stimulating agents (ESAs) used for chronic anemia management in patients with myelodysplastic syndromes (MDS) are commonly injected in a physician office but can be administered safely at home. In this study, we explored out-of-pocket (OOP) costs and receipt of Part D-covered ESAs in Medicare beneficiaries with MDS. MATERIALS AND METHODS: Patients with MDS enrolled in Medicare Parts A, B, and D were identified using diagnosis codes from 100% claims from 2006 to 2008. OOP costs for the mean erythropoietin alfa claim were compared for Parts B and D. Multivariable models examined the effect of low-income subsidy (LIS) and other Part D cost sharing on receipt of any ESA and any Part D-covered ESA. RESULTS: A total of 13,117 (62.9%) of 20,848 patients received ESAs, but only 1,436 (6.9%) had any Part D claim. OOP payment was $348 under Part D versus $161 under Part B. Among patients with ESA use, those with LIS were 4× more likely to receive Part D ESAs (P < .01). CONCLUSION: Few patients with MDS received ESAs through Part D. OOP payments required under Part D were substantially higher than under Part B. Cost sharing, as reflected by LIS receipt, likely affected decisions to prescribe ESAs outside of the physician office. Improved coordination between Part B and D benefits regarding issues of home injection of medications may create incentives that improve patient access and convenience and reduce costs associated with administration.

Assessing functional status and the survival benefit of chemotherapy for advanced non-small cell lung cancer using administrative claims data.

OBJECTIVES: Borderline or poor performance status (PS) patients comprise a significant proportion of those diagnosed with advanced non-small cell lung cancer (AdvNSCLC), but are often excluded from clinical trials. It is difficult to draw conclusions about the benefit of therapy in borderline PS patients due to lack of reliable PS assessments, and small clinical trial samples. Retrospective population-based secondary analyses may allow investigators to study under-represented populations in clinical trials. We hypothesized that patients with poor functional status derive benefit from chemotherapy compared good functional status, but that the magnitude of the benefit is lower compared to patients with good functional status. By utilizing a "disability status" (DS) measure as a proxy for PS, we offer a reliable mechanism for patient stratification that can be implemented in administrative claims data. METHODS: Medicare beneficiaries diagnosed with AdvNSCLC between 2001 and 2005 were selected from the Surveillance, Epidemiology and End Results database linked to Medicare claims. Disability status, a previously developed and validated claims-based proxy for baseline PS, was implemented. Patients were assigned to good versus poor DS. Cox proportional hazard models were used to examine the differential effects of chemotherapy for the two DS groups on all-cause mortality, controlling for tumor and patient characteristics. RESULTS: Most patients in the cohort (n=21,019) were ≥75 years of age (59%), and non-Hispanic white (85%); 91% were assigned to good DS; 38% received chemotherapy. Chemotherapy had a strong protective effect among good DS patients (hazard ratio, 0.43; CI 0.42-0.45; p<0.001), with a slightly smaller effect for poor DS (hazard ratio, 0.50; CI 0.44-0.57). CONCLUSIONS: Chemotherapy improves survival for advanced NSCLC patients with poor DS but to a lower magnitude than for good DS patients. The DS measure opens the door to assess outcomes for cancer patients with poor functional status using insurance claims data.

Effect of erythropoiesis-stimulating agent policy decisions on off-label use in myelodysplastic syndromes.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are widely used to treat anemia associated with myelodysplastic syndromes (MDS) as an off-label indication. In early 2007, the U.S. Food and Drug Administration (FDA) released safety alerts and mandated label changes, and the Centers for Medicare & Medicaid Services (CMS) implemented a National Coverage Determination (NCD) in August 2007, dramatically restricting ESA coverage based on specific clinical parameters in non-MDS patients. We sought to determine the effect on ESA use in MDS, examining both treatment initiation and concordance with guidelines designed to target patients most likely to benefit from therapy. METHODS: We determined receipt of ESA within 6 months of diagnosis. For ESA recipients, we operationalized three National Comprehensive Cancer Network guidelines: serum erythropoietin determination before ESA initiation, transfusion-independent at ESA initiation, and initial ESA treatment episode of >= 8 weeks. Logistic regression models tested the effect of time (half-year increments pre-post the August '07 CMS NCD implementation), controlling for demographics and health status. RESULTS: 17,491 (61.1%) of 28,627 beneficiaries with MDS received ESAs. ESA use increased prior to the reference period (Jan.-July 2007), but declined beginning in August 2007, the date of NCD implementation (marginal probability =-0.05, p-value<0.01). Concordance with treatment guidelines changed during the observation period, with increased rates of serum erythropoietin levels, but declined in the other two guidelines. CONCLUSION: These results suggest a mixed pattern of change in the face of the FDA safety warnings and CMS NCD in MDS and highlight the importance of monitoring for unintended consequences of policy changes.

Validation of disability status, a claims-based measure of functional status for cancer treatment and outcomes studies.

BACKGROUND: In prior research, we developed a claims-based prediction model for poor patient disability status (DS), a proxy measure for performance status, commonly used by oncologists to summarize patient functional status and assess ability of a patient to tolerate aggressive treatment. In this study, we implemented and validated the DS measure in 4 cohorts of cancer patients: early and advanced non-small cell lung cancers (NSCLC), stage IV estrogen receptor-negative (ER-) breast cancer, and myelodysplastic syndromes (MDS). DATA AND METHODS: SEER-Medicare data (1999-2007) for the 4 cohorts of cancer patients. Bivariate and multivariate logistic regression tested the association of the DS measure with designated cancer-directed treatments: early NSCLC (surgery), advanced NSCLC (chemotherapy), stage IV ER- breast cancer (chemotherapy), and MDS (erythropoiesis-stimulating agents). Treatment model fit was compared across model iterations. RESULTS: In both unadjusted and adjusted results, predicted poor DS was strongly associated with a lower likelihood of cancer treatment receipt in all 4 cohorts [early NSCLC (N=20,280), advanced NSCLC (N=31,341), stage IV ER- breast cancer (N=1519), and MDS (N=6058)] independent of other patient, contextual, and disease characteristics, as well as the Charlson Comorbidity Index. Inclusion of the DS measure into models already controlling for other variables did not significantly improve model fit across the cohorts. CONCLUSIONS: The DS measure is a significant independent predictor of cancer-directed treatment. Small changes in model fit associated with both DS and the Charlson Comorbidity Index suggest that unobserved factors continue to play a role in determining cancer treatments.

Lenalidomide performance in the real world: patterns of use and effectiveness in a Medicare population with myelodysplastic syndromes.

BACKGROUND: Lenalidomide is approved for the treatment of anemia with transfusion dependence (TD) in patients with lower-risk myelodysplastic syndrome (MDS) with 5q deletion (del5q-MDS), but its "real-life" use and effect on transfusion needs are unclear. In the current study, the authors examined its use in the Medicare population. METHODS: Patients with MDS who were enrolled in Medicare Parts A, B, and D were identified using International Classification of Diseases 9-Clinical Modification (ICD-9) codes from 100% Medicare claims from 2006 through 2008. Patients were followed until the end of the study or death. Claims were used to determine time to initiation of lenalidomide, daily dose, duration, and other MDS therapies. Transfusion status was defined each week based on transfusion use in rolling 8-week period: TD, required transfusions during 2 weeks, separated by ≥ 3 weeks; transfusion user (TU), 1 transfusion; and transfusion independence (TI), no transfusions. RESULTS: A total of 753 of 23,855 patients (3.2%) received lenalidomide, including 31% of 470 patients with del5q-MDS. At the time of lenalidomide initiation, 33% of patients were TD, 31% were TU, and 36% were TI. The median time to lenalidomide initiation was shorter for patients with del5q-MDS than for other lower-risk patients (8 weeks vs 20 weeks; P < .01). The percentage of patients with del5q-MDS receiving lenalidomide increased over time. Lenalidomide initiation was found to be negatively associated with older age and baseline diabetes, stroke, and renal disease. During the observation period, 44% of TU/TD patients (53% of the patients with del5q-MDS) achieved reductions in transfusion use; among TD patients receiving ≥ 3 cycles, 77% reduced their transfusion use and 40% achieved TI. CONCLUSIONS: To the authors' knowledge, the current study is the first report of lenalidomide use in a large Medicare-enrolled population with MDS. Reductions in transfusion rates were overall consistent with data from clinical trials. Response rates were higher when ≥ 3 lenalidomide cycles were received.

A novel approach to improve health status measurement in observational claims-based studies of cancer treatment and outcomes.

OBJECTIVES: To develop and provide initial validation for amultivariate, claims-based prediction model for disability status (DS), a proxymeasure of performance status (PS), among older adults. The model was designed to augment information on health status at the point of cancer diagnosis in studies using insurance claims to examine cancer treatment and outcomes. MATERIALS AND METHODS: We used data from the 2001­2005 Medicare Current Beneficiary Survey (MCBS), with observations randomly split into estimation and validation subsamples. We developed an algorithm linking self-reported functional status measures to a DS scale, a proxy for the Eastern Cooperative Oncology Group (ECOG) PS scale. The DS measure was dichotomized to focus on good [ECOG 0­2] versus poor [ECOG 3­4] PS. We identified potential claims-based predictors, and estimated multivariate logistic regression models, with poor DS as the dependent measure, using a stepwise approach to select the optimal model. Construct validity was tested by determining whether the predicted DS measure generated by the model was a significant predictor of survival within a validation sample from the MCBS. RESULTS AND CONCLUSION: One-tenth of the beneficiaries met the definition for poor DS. The base model yielded high sensitivity (0.79) and specificity (0.92); positive predictive value=48.3% and negative predictive value=97.8%, c-statistic=0.92 and good model calibration. Adjusted poor claims-based DS was associated with an increased hazard of death (HR=3.53, 95% CI 3.18, 3.92). The ability to assess DS should improve covariate control and reduce indication bias in observational studies of cancer treatment and outcomes based on insurance claims.

Patterns of erythropoiesis-stimulating agent use among Medicare beneficiaries with myelodysplastic syndromes and consistency with clinical guidelines.

Erythropoiesis-stimulating agents (ESA) are used commonly to reduce symptomatic anemia in patients with myelodysplastic syndromes (MDS). We assessed population-based patterns of ESA use relative to treatment guidelines using data from the Surveillance, Epidemiology, and End Results (SEER) registries, with linked Medicare claims providing detailed treatment data from 2001 through 2005. The study found widespread use (62%) of ESA in Medicare beneficiaries with MDS. Similar ESA use rates regardless of risk status, low frequency (45%) of serum erythropoietin determination prior to ESA initiation, and high prevalence (60.4%) of short-duration ESA episodes suggest clinically important discrepancies between actual practice and guideline-recommended therapy.

Tertiary center referral patterns for patients with myelodysplastic syndrome are indicative of age and race disparities: a single-institution experience.

Little is known about disparities in myelodysplastic syndromes (MDS). We performed a retrospective chart review of patients with MDS (n = 252) evaluated at the University of Maryland Greenebaum Cancer Center between 2000 and 2010. The median age at diagnosis was 65 years, which was lower than the median age of 76 years for patients with MDS in the Surveillance, Epidemiology and End Results database. Black males were younger than white males (62 vs. 68 years; p = 0.03) and had longer time to referral (9 vs. 1.5 months; p = 0.03), but black and white females did not differ in age or in time to referral. A difference in World Health Organization subtype classification was noted in black and white patients at diagnosis, but not at referral. There was no difference between all other pretreatment characteristics, treatment and survival by race. Our data suggest barriers to tertiary care referral for older patients and for black males.

Patient and physician characteristics associated with erythropoiesis-stimulating agent use in patients with myelodysplastic syndromes.

Patient and physician characteristics associated with use of erythropoiesis-stimulating agents in myelodysplastic syndrome patients have not yet been described. Myelodysplastic syndrome patients diagnosed from 2001 to 2005 were identified from the Surveillance Epidemiology and End Results-Medicare database. Multivariate regressions examined the association between patient and physician characteristics and the probability of receiving any erythropoiesis-stimulating agents, and of receiving therapeutic-length (≥ 8 week) treatment episodes. Among the 6,588 myelodysplastic syndrome patients studied, 65% received erythropoiesis-stimulating agents. Use of erythropoiesis-stimulating agents was lower for blacks compared to whites (OR 0.78; 95% CI:0.61-0.99), single persons compared to married (OR 0.77; 95% CI:0.62-0.97), Medicaid recipients (OR 0.66; 95% CI:0.55-0.79), and those living in census tracts with lower educational attainment. Patients who did not consult a hematology-oncology specialist were less likely to receive erythropoiesis-stimulating agents. Specialist access, financial resources and mobility are key determinants of receipt of erythropoiesis-stimulating agents among myelodysplastic syndrome patients.