Publications

IMPORTANCE: Using real-world data, the US Department of Veterans Affairs (VA) initiated a surveillance evaluation of edaravone after its approval for amyotrophic lateral sclerosis (ALS) in 2017. The use and safety of edaravone for patients with ALS in the VA health care system remain to be assessed.

OBJECTIVE: To describe a pharmacovigilance surveillance initiative with edaravone to monitor patient characteristics, utilization (edaravone cycles and riluzole use), and safety and to evaluate safety/effectiveness.

DESIGN, SETTING, AND PARTICIPANTS: This propensity score-matched cohort study used data on 369 patients with documented definite or probable ALS in the Veterans Health Administration (VHA) with at least 1 prescription for edaravone between August 1, 2017, and September 30, 2019. The analysis compared edaravone (alone or with riluzole) with riluzole only. For chronic users (≥6 months of drug), a time-to-event model evaluated ALS-related outcomes, with censoring at outcome, death, or end of evaluation. Patients with Parkinson disease, dementia, schizophrenia, or significant respiratory insufficiency per diagnosis codes within 2 years before prescription initiation were excluded. In overall matched cohorts, 223 patients treated with edaravone were 1:3 propensity score matched based on predefined confounders. For the chronic user subgroup analysis, 96 patients receiving edaravone and 424 patients receiving riluzole only were included.

EXPOSURES: Edaravone (alone or with riluzole) vs riluzole only.

MAIN OUTCOMES AND MEASURES: Patient characteristics, ALS drug use, and mortality. Acute outcomes (within 6 months of index) included proportion and mean time to event for death, discontinuation, or all-cause hospitalization, and outcomes for chronic users (receiving >6 months of treatment) included hazard ratios of outcomes related to disease-state progression.

RESULTS: Of 369 patients who received edaravone, most were older (mean [SD] age, 64.6 [11.3] years), male (346 [93.8%]), and White (261 [70.7%]). As of September 2019, 59.9% of edaravone patients had discontinued treatment; of those, 49.5% (108 of 218) received only 1 to 3 treatment cycles. Approximately 30% (110 patients) died. In a matched evaluation, significantly more acute all-cause hospitalization events occurred with edaravone (35.4% vs 22.0% for riluzole only); 72.6% of the edaravone cohort received edaravone with riluzole. Among chronic users, edaravone patients (70.8% edaravone with riluzole) had an increased hazard ratio of ALS-associated hospitalization (2.51; 95% CI, 1.18-8.16). The death rate was lower with edaravone but the difference was not statistically significant.

CONCLUSIONS AND RELEVANCE: Early edaravone discontinuation was common in the VA. Although outcomes favored use of riluzole only in the matched analysis, results should be interpreted with caution, as unmeasured bias in observational data is likely.

BACKGROUND: Rising medical costs are a significant concern for employers offering health benefits to employees, and there is interest in identifying insurance plan designs that optimize the effect of pharmacy benefits on overall costs. For instance, employers must decide between plans that carve in pharmacy benefits (where medical and pharmacy benefits are integrated into 1 package through an insurer) versus plans that carve out pharmacy benefits (where pharmacy benefits are separately administered through a pharmacy benefit manager). Little is known about the effect of carving in pharmacy benefits on medical utilization and costs.

OBJECTIVE: To compare the effect of carving in versus carving out pharmacy benefits on medical utilization, medical costs, and health management program participation in commercial health plans.

METHODS: We performed a propensity score-matched analysis comparing carve-in and carve-out members of a regional health plan in 2018. Our primary outcomes were medical utilization (annual medical claims/1,000 members) and costs (medical costs per member per month [PMPM]). We categorized these into the following domains: inpatient, emergency department, outpatient/ambulatory surgery, urgent care, primary care, specialist services, and diagnostics (laboratory testing/imaging). We additionally assessed participation in health plan-based health management programs.

RESULTS: We analyzed 9,633 carve-in members matched with 9,633 carve-out members. Compared with carving out pharmacy benefits, carving in was associated with 3.7% lower medical costs, with an $8.73 reduction in PMPM ($225.87 vs. $234.60), and no significant difference in medical utilization; significantly lower inpatient and urgent care claims (reduction of 9.29 claims/1,000 and 51.3 claims/1,000, respectively) and costs ($10.08 and $0.12 PMPM reduction, respectively); lower injectable medical therapy costs ($4.32 PMPM reduction); and higher durable medical equipment costs ($2.14 PMPM increase). Carve-in members also experienced 4.9% higher health management program participation.

CONCLUSIONS: As employers attempt to understand the value of carving in versus carving out pharmacy benefits to health plans, our findings suggest that carving in pharmacy benefits is associated with reduced medical costs and hospitalizations. Our findings can assist in informing employer decision-making processes and, as a result, reducing costs of care.

DISCLOSURES: No outside funding supported this study. Parekh was and Huang and Good are employed by the UPMC Centers for High-Value Health Care and Value-Based Pharmacy Initiatives. Manolis is employed by the UPMC Health Plan within the UPMC Insurance Services Division. Papa, Drnach, and Spiegel are employed by WorkPartners within the UPMC Insurance Services Division.

The Physician Payments Sunshine Act requires biomedical companies to report payments made to physicians and teaching hospitals to the Centers for Medicare and Medicaid Services (CMS). Despite significant attention paid to industry payments to physicians, little is known about payments to teaching hospitals, which create the potential for both benefits and institutional conflicts of interest. We examined 2018 CMS Open Payments program data to identify all nonresearch payments made by industry to teaching hospitals and determined that 91 percent of teaching hospitals received industry payments totaling $832 million in 2018. We observed substantial royalty payments, which may reflect the downstream benefits of research partnerships, as well as substantial payments for gifts and education, which raise concerns for institutional conflicts of interest. Hospital predictors of receiving payments included large bed size, major medical school affiliation, and inclusion on the U.S. News & World Report Best Hospitals Honor Roll. Financial payments from industry to teaching hospitals are common and previously underrecognized. Hospitals should strengthen policies to prevent the institutional conflicts of interest that may arise from these payments while promoting beneficial industry collaborations. We also suggest that CMS reporting requirements be broadened to all hospitals to meet the Sunshine Act's goals of encouraging transparency and preventing inappropriate industry influence.

OBJECTIVE: To identify sociodemographic profiles of patients prescribed high-dose opioids.

DESIGN: Cross-sectional cohort study.

SETTING/PATIENTS: Veterans dually-enrolled in Veterans Health Administration and Medicare Part D, with ≥1 opioid pre-scription in 2012.

MAIN OUTCOME MEASURES: We identified five patient-level demographic characteristics and 12 community variables re-flective of region, socioeconomic deprivation, safety, and internet connectivity. Our outcome was the proportion of vet-erans receiving >120 morphine milligram equivalents (MME) for ≥90 consecutive days, a Pharmacy Quality Alliance measure of chronic high-dose opioid prescribing. We used classification and regression tree (CART) methods to identify risk of chronic high-dose opioid prescribing for sociodemographic subgroups.

RESULTS: Overall, 17,271 (3.3 percent) of 525,716 dually enrolled veterans were prescribed chronic high-dose opioids. CART analyses identified 35 subgroups using four sociodemographic and five community-level measures, with high-dose opioid prescribing ranging from 0.28 percent to 12.1 percent. The subgroup (n = 16,302) with highest frequency of the outcome included veterans who were with disability, age 18-64 years, white or other race, and lived in the Western Census region. The subgroup (n = 14,835) with the lowest frequency of the outcome included veterans who were with-out disability, did not receive Medicare Part D Low Income Subsidy, were >85 years old, and lived in communities within the second and sixth to tenth deciles of community public assistance.

CONCLUSIONS: Using CART analyses with sociodemographic and community-level variables only, we identified sub-groups of veterans with a 43-fold difference in chronic high-dose opioid prescriptions. Interactions among disability, age, race/ethnicity, and region should be considered when identifying high-risk subgroups in large populations.

In an effort to demonstrate measurable value of pharmaceuticals in the United States, many payers and drug manufacturers have entered into value-based purchasing contracts that link payment for prescription medications to patient outcomes, creating shared risk between the 2 entities. These agreements have emerged as part of a larger movement within the health care landscape to transition away from volume-based payment models and towards value-based designs that promote high-quality and affordable care. Key to the success of pharmaceutical value-based contracting is agreement on meaningful and measurable outcomes that reflect drug performance. Traditional value-based contracts are developed by pharmaceutical companies and payers and may not reflect values of other important stakeholders, such as patients, providers, and employers (when applicable). One approach to more effectively align the interests of all key stakeholders and to maximize the effect and transparency of value-based pharmaceutical contracts is to use the validated Delphi surveying technique, which can gather information and build stakeholder consensus on key elements before contract development. In this Viewpoints article, we describe our experience conducting Delphi studies in 5 disease contexts to inform pharmaceutical value-based contract development, including insights learned and practical considerations for real-world application. In addition, we outline advantages to using this validated consensus-building tool to solicit vital and underrepresented stakeholder input, foster transparency in the contract development process, and promote shared learning for future value-based initiatives. DISCLOSURES: No outside funding supported this project. All authors are or were employed by UPMC Health Plan at the time of this study and have no other disclosures to declare.

OBJECTIVE: To identify meaningful migraine outcome measures among key stakeholders to inform value-based contracts for migraine medications.

BACKGROUND: Value-based contracts linking medication payments to predefined performance metrics aim to promote value through aligned incentives and shared risk between manufacturers and payers. The emergence of new and expensive pharmaceuticals for migraine presents an opportunity for value-based contract development. However, uncertainty remains around which outcomes are most meaningful to all migraine stakeholders.

METHODS: This study utilized a Delphi survey to incorporate views from 82 stakeholders, including patients (n = 21), providers (n = 23), payers (n = 10), employers (n = 18), and pharmaceutical company representatives (n = 10). A list of 15 migraine-related outcomes was created from a literature review and subject matter expert consultation. Stakeholders reported on the value of these outcomes through a 5-point Likert scale and selection of their top 3 most meaningful outcomes. All participants except patients and employers also used a 5-point Likert scale to rate the feasibility of collecting each outcome measure. Consensus was defined as ≥75% agreement on the importance and feasibility of an outcome (Likert scores ≥4/5 or selection of an outcome as most meaningful).

RESULTS: After 2 rounds, consensus was achieved for importance of 9 outcomes on the Likert scale. "Decrease in migraine frequency" reached 100% agreement (82/82), followed by "increased ability to resume normal activities" (96%, 79/82). When asked to choose the 3 most meaningful outcomes, stakeholders selected "decrease in migraine frequency" (88%, 72/82) followed by "decrease in migraine severity" (80%, 66/82). The 2 measures rated as most feasibly collected were "decrease in emergency department/urgent care visits" (95%, 40/42) and "decrease in migraine frequency" (90%, 38/42). There were statistically significant differences between non-patient and patient stakeholders in selection of "decrease in emergency department/urgent care visits" [20% (12/61) vs 0% (0/21), P = .031]; and employer and patient stakeholders in selection of "decrease in work days missed" [44% (8/18) vs 5% (1/21), P = .006] and "decrease in emergency department/urgent care visits" [22% (4/18) vs 0% (0/21), P = .037] as most meaningful outcomes.

CONCLUSIONS: The measures "decrease in migraine frequency" followed by "decrease in migraine severity" were identified as top priority migraine outcome measures.

IMPORTANCE: The shift toward value-based care has placed emphasis on preventive care and chronic disease management services delivered by multidisciplinary health care teams. Community pharmacists are particularly well positioned to deliver these services due to their accessibility.

OBJECTIVE: To compare the number of patient visits to community pharmacies and the number of encounters with primary care physicians among Medicare beneficiaries who actively access health care services.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed a 5% random sample of 2016 Medicare beneficiaries from January 1, 2016, to December 31, 2016 (N = 2 794 078). Data were analyzed from October 23, 2019, to December 20, 2019. Medicare Part D beneficiaries who were continuously enrolled and had at least 1 pharmacy claim and 1 encounter with a primary care physician were included in the final analysis (n = 681 456). Those excluded from the study were patients who were not continuously enrolled in Part D until death, those with Part B skilled nursing claims, and those with Part D mail-order pharmacy claims.

EXPOSURES: We conducted analyses for the overall sample and for subgroups defined by demographics, region of residence, and clinical characteristics.

MAIN OUTCOMES AND MEASURES: Outcomes included the number of visits to community pharmacies and encounters with primary care physicians. Unique visits to the community pharmacy were defined using a 13-day window between individual prescription drug claims. Kruskal-Wallis tests were used to compare the medians for the 2 outcomes.

RESULTS: A total of 681 456 patients (mean [SD] age, 72.0 [12.5] years; 418 685 [61.4%] women and 262 771 [38.6%] men) were included in the analysis; 82.2% were white, 9.6% were black, 2.4% were Hispanic, and 5.7% were other races/ethnicities. Visits to the community pharmacy outnumbered encounters with primary care physicians (median [interquartile range (IQR)], 13 [9-17] vs 7 [4-14]; P < .001). The number of pharmacy visits was significantly larger than the number of primary care physician encounters for all subgroups evaluated except for those with acute myocardial infarction (median [IQR], 15 [12-19] vs 14 [7-26]; P = .60 using a 13-day window). The difference in the number of pharmacy and primary care physician encounters was larger in rural areas (median [IQR], 14 [10-17] vs 5 [2-11]; P < .001) than in metropolitan areas (median [IQR], 13 [8-17] vs 8 [4-14]; P < .001). In all 50 states and in all but 9 counties, the number of community pharmacy visits was larger than the number of encounters with primary care physicians.

CONCLUSIONS AND RELEVANCE: This cross-sectional study suggests that community pharmacists are accessible health care professionals with frequent opportunities to interact with community-dwelling patients. Primary care physicians should work collaboratively with community pharmacists, who can assist in the delivery of preventive care and chronic disease management.

BACKGROUND: Millions of American adults do not receive the recommended vaccinations each year. Community pharmacies are well positioned to help fill this gap through easy access and innovative patient-centered interventions. The primary goal of this demonstration project was to implement new notification and motivational interviewing processes at a regional supermarket chain pharmacy to increase the number of influenza, pertussis, pneumococcal, and herpes zoster vaccines provided to adults.

METHODS: This prospective, observational project utilized a pre-post design. Algorithms were developed with pharmacy dispensing data to identify vaccine-eligible patients. Pharmacy staff then received automated notifications through one of the following: (1) a vaccine message printed on the prescription receipt or on paper attached to the prescription bag when patients came to the pharmacy; or (2) a patient list generated through commercially-available software listing patient contact information and which vaccine they were eligible to receive. Irrespective of the notification process, pharmacy staff employed motivational interviewing techniques either face-to-face or telephonic to engage patients in conversation about getting vaccinated. Finally, an interface to the statewide vaccination registry was developed and tested to transmit vaccination information from all pharmacy locations.

RESULTS: Ninety-nine pharmacies participated in the demonstration project across western Pennsylvania. A 33% increase in vaccinations was recorded over the prior year. Increases in vaccines were demonstrated in three of the four vaccine types: 45% for influenza, 31% for pertussis, and 7% for pneumococcal vaccinations. A decrease of 5% was observed for herpes zoster vaccinations. A successful connection to the statewide vaccine registry was established and 100% of all vaccines administered were transmitted to the registry.

CONCLUSION: A combination of face-to-face and telephonic interventions with motivational interviewing were successful at increasing adult vaccinations in a regional supermarket chain pharmacy. Equal and sustained prioritization for all vaccines is necessary to achieve increases across all vaccine types.