Publications

BACKGROUND: The objective of this study is to describe the use of targeted therapies for the treatment of advanced renal cell carcinoma (RCC) and overall survival (OS) among patients in clinical practice in the Veterans Health Administration (VHA).

METHODS: A retrospective cohort of 286 patients from 24 VHA Medical Centers diagnosed with advanced clear cell RCC between Fiscal Year (FY) 2010 and FY2014 was followed through September 30, 2016. Among patients who received targeted therapy, we described the medications taken, duration of therapy, and overall survival. We also assessed the effect of the first therapy received on overall survival using Cox Proportional Hazards models.

RESULTS: There were 66 patients who did not receive therapy for their advanced RCC. Of the 220 treated patients, the mean (sd) number of medications received was 1.9 (1.1). The medications most commonly used first were sunitinib (61.8%), pazopanib (17.3%), and temsirolimus (10.9%). The median duration of first-line therapy was 86 days (interquartile range [IQR] 42, 210). Median total duration of therapy was 159 days (IQR 58, 397). 62.3% of patients had ≥ 1 dose of therapy held or reduced, mainly due to an adverse drug event (ADE). Median survival from the start of treatment to death was 1.08 years (IQR 0.80, 1.31). Finally, receipt of temsirolimus vs sunitinib (HR 1.95 [95%CI 1.09,3.47]) as the first targeted therapy was independently associated with an increased hazard of death.

CONCLUSION: Our analysis of targeted therapies for advanced RCC in VHA suggests duration of treatment is shorter in a real-world setting than in clinical trials, and dose reductions and ADEs are more common.

IMPORTANCE: Before 2009, only 4 self-administered disease-modifying therapies (DMTs) were approved for the treatment of multiple sclerosis (MS). Since then, 7 new agents have entered the market.

OBJECTIVE: To assess trends in prices, market share, and spending on self-administered DMTs for MS in Medicare Part D from 2006 through 2016.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used claims data from 2006 through 2016 from a 5% random sample of Medicare beneficiaries (a mean of 2.8 million Medicare beneficiaries per year). All prescription claims for self-administered DMTs for MS (glatiramer acetate, interferon beta-1a, interferon beta-1b, fingolimod hydrochloride, teriflunomide, dimethyl fumarate, and peginterferon beta-1a) were extracted throughout the study period.

MAIN OUTCOMES AND MEASURES: The main outcomes were the annual cost of treatment with each medication, based on Medicare Part D prescription claims gross costs and US Food and Drug Administration-approved recommended dosing; market share of each medication, defined as the proportion of pharmaceutical spending accounted by every drug; and pharmaceutical spending per 1000 Medicare beneficiaries for all drugs. The relative contributions of Medicare Part D Plans' payments, Medicare catastrophic coverage payments, low-income cost-sharing subsidies, patients' out-of-pocket costs, manufacturers' coverage gap discounts, and other payments toward pharmaceutical spending were further quantified.

RESULTS: Annual costs of treatment with self-administered DMTs for MS more than quadrupled from 2006 to 2016, from a mean (SD) of $18 660 ($1177) to $75 847 ($16 956) and at a mean rate of 12.8% every year. Brand-name glatiramers accounted for the largest market share across the study period, ranging between $25 552 of $79 411 per 1000 Medicare beneficiaries (32.2%) and $10 342 of $21 365 per 1000 Medicare beneficiaries (48.4%). Platform therapies experienced a substantial drop from 2006 to 2016 in favor of newer therapies, with decreases in the market shares of brand-name glatiramers (per 1000 Medicare beneficiaries: $2861 of $7794 [36.7%] to $25 552 of $79 411 [32.2%]), interferon beta-1a (30 µg; per 1000 Medicare beneficiaries: $2521 of $7794 [32.3%] to $11 298 of $79 411 [14.2%]), interferon beta-1b (Betaseron; per 1000 Medicare beneficiaries: $1460 of $7794 [18.7%] to $3588 of $79 411 [4.5%]), and interferon beta-1a (8.8/22/44 µg; per 1000 Medicare beneficiaries: $951 of $7794 [12.2%] to $6588 of $79 411 [8.3%]) and increases in fingolimod (to $6311 of $79 411 per 1000 Medicare beneficiaries [7.9%]), teriflunomide (to $7177 of $79 411 per 1000 Medicare beneficiaries [9.0%]), and dimethyl fumarate (to $15 262 of $79 411 per 1000 Medicare beneficiaries [19.2%]). Throughout the study period, pharmaceutical spending per 1000 beneficiaries increased 10.2-fold (from $7794 to $79 411), and out-of-pocket patient spending per 1000 beneficiaries increased 7.2-fold (from $372 to $2673). The relative contribution of federal payments toward pharmaceutical spending increased from $5335 of $7794 (68.5%) to $58 620 to $79 411 (73.8%).

CONCLUSIONS AND RELEVANCE: Per this analysis, prices of self-administered DMTs for MS increased dramatically between 2006 and 2016. This resulted in a 7.2-fold increase in patient out-of-pocket costs.

IMPORTANCE: Drug safety communications released by the US Food and Drug Administration (FDA) are often based on limited evidence on safety signals after approval. Varenicline may serve as a relevant case study because it was the target of several FDA communications in 2008 and 2009; ultimately, the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) dismissed safety concerns on increased suicidal thoughts and aggressive and erratic behavior on December 16, 2016.

OBJECTIVE: To examine the association between FDA drug safety communications and the use of varenicline.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective, longitudinal, cross-sectional study of Veterans Health Administration (VHA) outpatient data from October 1, 2001, through December 31, 2018, and Medicaid drug state use data from July 1, 2006, through September 30, 2018, on varenicline prescribing.

MAIN OUTCOMES AND MEASURES: Prescribing records for varenicline and nicotine replacement therapy (NRT) in the VHA were extracted, and the number of unique varenicline and NRT users in the VHA per quarter was measured. An interrupted time series analysis was performed to describe the association between FDA safety warnings and the use of varenicline and NRT. To test the generalizability of the findings, similar analyses were conducted using the number of prescriptions reimbursed for varenicline by Medicaid every quarter in 2006-2018.

RESULTS: After its addition to the VHA national drug formulary in January 2007, varenicline use presented a steady increase, reaching a peak of 32 581 quarterly unique users in the first quarter of 2008. Within 12 months of the February 1, 2008, public health advisory, quarterly varenicline use in VHA patients decreased by 68.7% (from 32 581 to 10 182 patients; P < .001 for slope change), and NRT use increased by 32.1% (from 55 728 to 73 629 patients; P < .001 for slope change). In Medicaid prescriptions, varenicline use decreased by 38.0% (from 109 308 to 67 761 prescriptions; P < .001 for slope change) within 12 months of the 2008 public health advisory. Twelve months after the publication of the EAGLES trial, which showed no significant increase in psychiatric/behavioral effects with varenicline relative to NRT, use of varenicline increased by 42.7% in VHA patients (from 9251 to 13 199 patients; P = .01 for slope change) and by 26.0% in Medicaid prescriptions (112 063 to 141 122; P = .26 for slope change ).

CONCLUSIONS AND RELEVANCE: With use of varenicline as a case study, early communications from the FDA and VHA followed by a labeling change appeared to be associated with a considerable decrease in drug use, which may have been associated with negative public health consequences.

BACKGROUND: The 2014 Veterans Access, Choice and Accountability Act (i.e., "Choice") allows eligible Veterans to receive covered health care outside the Veterans Affairs (VA) Healthcare System. The initial implementation of Choice was challenging, and use was limited in the first year.

OBJECTIVE: To assess satisfaction with Choice, and identify reasons for satisfaction and dissatisfaction during its early implementation.

DESIGN AND PARTICIPANTS: Semi-structured telephone interviews from July to September 2015 with Choice-eligible Veterans from 25 VA facilities across the USA.

MAIN MEASURES: Satisfaction was assessed with 5-point Likert scales and open-ended questions. We compared ratings of satisfaction with Choice and VA health care, and identified reasons for satisfaction/dissatisfaction with Choice in a thematic analysis of open-ended qualitative data.

RESULTS: Of 195 participants, 35 had not attempted to use Choice; 43 attempted but had not received Choice care (i.e., attempted only); and 117 attempted and received Choice care. Among those who attempted only, a smaller percentage were somewhat/very satisfied with Choice than with VA health care (17.9% and 71.8%, p < 0.001); among participants who received Choice, similar percentages were somewhat/very satisfied with Choice and VA health care (66.6% and 71.1%, p = 0.45). When asked what contributed to Choice ratings, participants who attempted but did not receive Choice care reported poor access (50%), scheduling problems (20%), and care coordination issues (10%); participants who received Choice care reported improved access (27%), good quality of care (19%), and good distance to Choice provider (16%). Regardless of receipt of Choice care, most participants expressed interest in using Choice in the future (70-82%).

CONCLUSIONS: Access and scheduling barriers contributed to dissatisfaction for Veterans unsuccessfully attempting to use Choice during its initial implementation, whereas improved access and good care contributed to satisfaction for those receiving Choice care. With Veterans' continued interest in using services outside VA facilities, subsequent policy changes should address Veterans' barriers to care.

In this cohort study, pricing data from January 2007 to June 2018 from SSR Health were used to determine how list prices, net prices, and discounts for the originator biologics changed with biosimilar competition.

BACKGROUND: There is systemic undercoding of medical comorbidities within administrative claims in the Department of Veterans Affairs (VA). This leads to bias when applying claims-based risk adjustment indices to compare outcomes between VA and non-VA settings. Our objective was to compare the accuracy of a medication-based risk adjustment index (RxRisk-VM) to diagnostic claims-based indices for predicting mortality.

METHODS: We modified the RxRisk-V index (RxRisk-VM) by incorporating VA and Medicare pharmacy and durable medical equipment claims in Veterans dually-enrolled in VA and Medicare in 2012. Using the concordance (C) statistic, we compared its accuracy in predicting 1 and 3-year all-cause mortality to the following models: demographics only, demographics plus prescription count, or demographics plus a diagnostic claims-based risk index (e.g., Charlson, Elixhauser, or Gagne). We also compared models containing demographics, RxRisk-VM, and a claims-based index.

RESULTS: In our cohort of 271,184 dually-enrolled Veterans (mean age = 70.5 years, 96.1% male, 81.7% non-Hispanic white), RxRisk-VM (C = 0.773) exhibited greater accuracy in predicting 1-year mortality than demographics only (C = 0.716) or prescription counts (C = 0.744), but was less accurate than the Charlson (C = 0.794), Elixhauser (C = 0.80), or Gagne (C = 0.810) indices (all P < 0.001). Combining RxRisk-VM with claims-based indices enhanced its accuracy over each index alone (all models C ≥ 0.81). Relative model performance was similar for 3-year mortality.

CONCLUSIONS: The RxRisk-VM index exhibited a high level of, but slightly less, accuracy in predicting mortality in comparison to claims-based risk indices.

IMPLICATIONS: Its application may enhance the accuracy of studies examining VA and non-VA care and enable risk adjustment when diagnostic claims are not available or biased.

LEVEL OF EVIDENCE: Level 3.

PURPOSE: Many medications that were marketed prior to 1962 but lack Food and Drug Administration (FDA) approval are prescribed in the United States. Usage patterns of these "unapproved medications" are poorly elucidated, which is concerning due to potential lack of data on safety and efficacy. The purpose of this project was to characterize purchases of unapproved medications within the Veterans Health Administration (VHA) by type, frequency, and cost.

METHODS: VHA purchasing databases were used to create a list of all products with National Drug Codes (NDCs) purchased nationwide in fiscal year 2016 (FY16). This list was compared to FDA databases to identify unapproved prescription medications. For each identified combination of active pharmaceutical ingredient (API) and route of administration ("API/route combination"), numbers of packages purchased and associated costs were added.

RESULTS: VHA pharmacy purchasing records contained 3,299 unapproved products with NDCs in FY16. After excluding equipment, nutrition products, compounding ingredients, nonmedication products, and duplicate NDCs, there were 600 unique NDCs associated with 130 distinct API/route combinations. The most commonly acquired product was prescription sodium fluoride dental paste (350,775 packages). The greatest pharmaceutical expenditure was for sodium hyaluronate injection ($24.5 million). Unapproved products accounted for less than 1% of overall VHA pharmacy purchasing in FY16.

CONCLUSION: VHA purchased many unapproved prescription products in FY16 but is taking action to address use of such products in consideration of safety and efficacy data and available alternatives.

OBJECTIVE: The objective of this study was to determine strategies to implement influenza pandemic vaccinations effectively at grocery store chain community pharmacies.

METHODS: Clinical pharmacy coordinators and pharmacy managers representing 3 grocery store chain community pharmacies across Pennsylvania were identified for participation in semistructured telephone interviews. Interviews were audio-recorded and transcribed. Transcripts were independently coded by 2 investigators and coding discrepancies were resolved. A thematic analysis was conducted, and supporting quotes were selected for each theme.

RESULTS: Twelve pharmacists participated in the interviews, which were conducted from September 2016 to November 2017. Five key themes were identified: (1) mobilize pharmacy staff members to specific locations to prepare for a high volume of vaccinations; (2) implement vaccination clinics during high-volume scenarios; (3) utilize nonpharmacy spaces to increase vaccination capabilities; (4) determine vaccine distribution by highest risk populations that each pharmacy serves; and (5) conduct training customized to the pharmacy chain that supplements national pandemic influenza training.

CONCLUSION: Grocery store chain community pharmacies are desirable sites for pandemic vaccination because of a variety of factors, such as space and staffing flexibility. Developing a pandemic vaccination plan will enable community pharmacists to contribute more effectively during influenza pandemics.

OBJECTIVE: To garner experience with the early implementation of pharmacist-provided comprehensive medication management at a regional supermarket pharmacy during the initial launch of a statewide community pharmacy enhanced services network payer contract.

METHODS: A series of key informant interviews were conducted with pharmacists at Giant Eagle Pharmacy locations in Pennsylvania. To be eligible to participate, pharmacists must have been trained by the Pennsylvania Pharmacists Care Network to deliver contracted comprehensive medication management services and willing to participate in audio recorded, telephonic interviews every 2 weeks. Interviews concluded when each pharmacist completed a total of 6 interviews or when the project period ended. A semistructured interview guide was developed by the investigators to elicit the pharmacists' experience providing contracted services. Interviews were transcribed and coded by 2 independent investigators. Coding discrepancies were resolved. The final coded transcripts were presented back to the project team to identify and finalize major themes. Illustrative quotes were selected to represent each theme.

RESULTS: Interviews from 10 pharmacists were included in the analysis. Five themes emerged as keys of successful early implementation: (1) promote commitment of the pharmacy team, (2) use effective whole-team patient engagement strategies, (3) personalize patient encounters by providing patient-centered care and practicing interpersonal skills, (4) make workflow and staffing resources easily accessible, and (5) make clinical patient care tools readily available.

CONCLUSION: These results highlight thematic trends for how pharmacists can successfully engage their patients in contracted comprehensive medication management services. Understanding the success of early implementation at a regional supermarket pharmacy can serve as a framework for other participants in community pharmacy enhanced services networks to replicate and scale contracted patient care services.