Early Mortality After the First Dose of COVID-19 Vaccination: A Target Trial Emulation.

BACKGROUND: Vaccine hesitancy persists alongside concerns about the safety of coronavirus disease 2019 (COVID-19) vaccines. We aimed to examine the effect of COVID-19 vaccination on risk of death among US veterans. METHODS: We conducted a target trial emulation to estimate and compare risk of death up to 60 days under two COVID-19 vaccination strategies: vaccination within 7 days of enrollment versus no vaccination through follow-up. The study cohort included individuals aged ≥18 years enrolled in the Veterans Health Administration system and eligible to receive a COVID-19 vaccination according to guideline recommendations from 1 March 2021 through 1 July 2021. The outcomes of interest included deaths from any cause and excluding a COVID-19 diagnosis. Observations were cloned to both treatment strategies, censored, and weighted to estimate per-protocol effects. RESULTS: We included 3 158 507 veterans. Under the vaccination strategy, 364 993 received vaccine within 7 days. At 60 days, there were 156 deaths per 100 000 veterans under the vaccination strategy versus 185 deaths under the no vaccination strategy, corresponding to an absolute risk difference of -25.9 (95% confidence limit [CL], -59.5 to 2.7) and relative risk of 0.86 (95% CL, .7 to 1.0). When those with a COVID-19 infection in the first 60 days were censored, the absolute risk difference was -20.6 (95% CL, -53.4 to 16.0) with a relative risk of 0.88 (95% CL, .7 to 1.1). CONCLUSIONS: Vaccination against COVID-19 was associated with a lower but not statistically significantly different risk of death in the first 60 days. These results agree with prior scientific knowledge suggesting vaccination is safe with the potential for substantial health benefits.

Association of Neighborhood Disadvantage and Anticoagulation for Patients with Atrial Fibrillation in the Veterans Health Administration: the REACH-AF Study.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia, the management of which includes anticoagulation for stroke prevention. Although disparities in anticoagulant prescribing have been well documented for individual socioeconomic factors, less is known about the association of neighborhood-level disadvantage and anticoagulation for AF. OBJECTIVE: To assess the association between neighborhood disadvantage and anticoagulant initiation for patients with incident AF. DESIGN: Retrospective cohort study. PARTICIPANTS: A cohort of patients enrolled in the Veterans Health Administration (VA) with incident AF from January 2014 through December 2020 from the Race, Ethnicity, and Anticoagulant CHoice in Atrial Fibrillation (REACH-AF) Study. MAIN MEASURES: The primary exposure was neighborhood disadvantage quantified using area deprivation index (ADI), classified by quintiles (Q). The outcomes were initiation of any anticoagulant therapy (warfarin or direct oral anticoagulant, DOAC) within 90 days of AF diagnosis and DOAC use among initiators. We used mixed effects logistic regression to assess the association between ADI and anticoagulant therapy, incorporating a fixed effect for treatment site and baseline patient, provider, and facility covariates. KEY RESULTS: Among 161,089 patients, 105,489 (65.5%) initiated any anticoagulant therapy, and 78,903 (74.8%) used DOACs. Any anticoagulant therapy increased 3.2 percentage points (63.0% to 66.2%; p<.001) from Q1 to Q5, whereas DOAC use decreased 8.2 percentage points (79.4% to 71.2%; p<.0001) across quintiles. The adjusted odd ratios of any anticoagulant therapy were non-significantly different for Q2-Q5 than Q1. The adjusted odds of DOAC use decreased progressively from 0.89 (95% CI, 0.84-0.94) in Q2 to 0.77 (95% CI, 0.73-0.83) in Q5 compared to Q1 (p<.0001). CONCLUSIONS: Among Veterans with incident AF, we observed similar initiation of any anticoagulant, though neighborhood deprivation was associated with decreased DOAC use among anticoagulant initiators. Future interventions to improve pharmacoequity in anticoagulant prescribing for AF should consider the role of neighborhood-level determinants of health inequities.

Impact of the COVID-19 pandemic on new starts to oral oncology medications in the US.

INTRODUCTION: The COVID-19 pandemic has had a significant impact on healthcare delivery. Although others have documented the impact on new cancer diagnoses, trends in new starts for oncology drugs are less clear. We examined changes in new users of oral oncology medications in the US following COVID-19 stay-at-home orders in 2020 compared to prior years. METHODS: We examined prescription data for members enrolled with a national pharmacy benefits manager in the US from January 1-October 31 of 2018, 2019, and/or 2020. This is a retrospective, observational study comparing new users per 100,000 members per month for all oral oncology drugs, and separately for breast, lung, and prostate cancer, leukemia, and melanoma oral drugs. We performed a difference-in-differences analysis for change in new users from pre-period (prior to pandemic-induced disruption, January-March), to post-period (following pandemic-induced disruption, April-October), between 2020 and 2019, and 2020 and 2018. RESULTS: New oral oncology drug users per 100,000 members per month declined by an additional 11.3% in the 2020 post-period compared to 2019 (p = 0.048). New oral breast cancer drug starts declined by an additional 14.0% in the 2020 post-period compared to 2019 (p = 0.040). Similar but non-significant trends were found between 2020 and 2018. No significant differences were found between post-period monthly new starts of leukemia, melanoma, lung or prostate cancer disease-specific oral medications. CONCLUSIONS: Long-term implications of delays in cancer treatment initiation are unclear, although there is concern that patient outcomes may be negatively impacted.

Assessing the impact of adding pharmacist management services to an existing discharge planning program on 30-day readmissions.

BACKGROUND: Although hospital readmission rates are declining nationally, avoidable readmissions remain a public health concern. Effective readmission interventions are multifaceted and include discharge planning and transition-of-care coordination. Clinical pharmacists are effective contributors to these processes, bringing expertise to discharge counseling, medication reconciliation, medication adherence, and postdischarge follow-up counseling. OBJECTIVE: We evaluated the impact of adding health plan clinical pharmacy management services to an existing discharge program on all-cause readmissions and postdischarge primary physician visits. METHOD: Pharmacy management services by health plan clinical pharmacists of a large regional integrated delivery system were added to an existing optimal discharge planning (ODP) program. Criteria for eligibility for these pharmacists' services included patients who prescribed a new maintenance medication after discharge, received a therapeutic substitution, had a previous discharge within 30 days, or were taking a high-risk medication. A retrospective, observational analysis of a subgroup of patients, who received the pharmacy management services as part of ODP, was performed using a difference-in-difference model, by comparing propensity-matched discharges from February 22, 2016, to January 31, 2017 (preprogram implementation) with discharges from February 22, 2017, to January 31, 2018 (implementation period), to estimate changes in 30-day readmission rates and postdischarge primary physician visits. RESULTS: A total of 111 of the propensity matched received the pharmacy management services; of these, 73% (ODP) versus 64% (non-ODP) were ≥58 years, 60% were females, and 62% (ODP) versus 52% (non-ODP) were Medicare beneficiaries. There was a 16.7% (P = 0.022) statistically significant reduction in combined inpatient and observation 30-day readmissions and a 19.7% increase in 5-day postdischarge follow-up physician visits (P = 0.037) for the subgroup who also received the pharmacy management services. CONCLUSION: Addition of pharmacist management services to an existing hospital discharge program for select at-risk patients was associated with reduced inpatient and observation 30-day readmissions.

Trends in utilization and costs of migraine medications, 2017-2020.

OBJECTIVE: This study examines changes in utilization and costs trends associated with migraine medications. BACKGROUND: Migraine attacks are a burden to many patients. There are many pharmacotherapy options available with newer migraine drug classes entering the market in the past decade. Little is known about the use, associated costs, and the impact of the newer agents. METHODS: This retrospective, cross-sectional study examined 2017-2020 administrative claims from a large national pharmacy benefits manager. Patients aged ≥ 18 years enrolled in commercial, Medicare, Medicaid, or health insurance exchange insurance plans who filled ≥ 2 prescription claims for triptans, ergotamines, isometheptenes, gepants, ditans, and CGRP mABs were included. A two-sample t-test was conducted to estimate whether differences in mean utilization and costs between 2017 and 2020 were statistically significant for migraine drug classes, except for CGRP mABs, which were estimated between 2018 and 2020. RESULTS: The sample ranged from 161,369 (2017) to 240,330 (2020) patients. 84.5% (n = 203,110; 2020) of patients were women. The number of 30-day adjusted prescription fills for prophylaxis remained stable over the four-year period, except for CGRP mABs, which increased from 0.5% (n = 0.007; 2018) to 5.3% (n = 0.075; 2020). Antiepileptics, antidepressants and beta blockers were the most common prophylaxes, while triptans, non-steroidal anti-inflammatory drugs/non-narcotic analgesics and opioids were the most common treatments utilized. CGRP mABs were the most expensive, while utilization of triptans were the highest. CGRP mABs had the largest increase in utilization (177.5%) and costs (166.3%) PPPM in 2020 ($291.17) compared to 2018 ($109.35), the year they were first available (p < 0.001). Between 2018 and 2020, costs increased overall and for commercial and Medicare enrollees, but remained unchanged for Medicaid and HIX members. CONCLUSION: Our study demonstrates a shift in migraine medication utilization from 2017-2020, where increased use of CGRP mABs had a significant contribution to increased costs. These increased pharmacy costs must be weighed against the improved tolerability of these agents likely resulting in other healthcare and indirect cost savings.

Medication Treatment of Active Opioid Use Disorder in Veterans With Cirrhosis.

INTRODUCTION: Although opioid use disorder (OUD) is common in patients with cirrhosis, it is unclear how medication treatment for OUD (MOUD) is used in this population. We aimed to assess the factors associated with MOUD and mortality in a cohort of Veterans with cirrhosis and OUD. METHODS: Within the Veterans Health Administration Corporate Data Warehouse, we developed a cohort of Veterans with cirrhosis and active OUD, using 2 outpatient or 1 inpatient International Classification of Diseases, ninth revision codes from 2011 to 2015 to define each condition. We assessed MOUD initiation with methadone or buprenorphine over the 180 days following the first OUD International Classification of Diseases, ninth revision code in the study period. We fit multivariable regression models to assess the association of sociodemographic and clinical factors with receiving MOUD and the associations between MOUD and subsequent clinical outcomes, including new hepatic decompensation and mortality. RESULTS: Among 5,600 Veterans meeting criteria for active OUD and cirrhosis, 722 (13%) were prescribed MOUD over 180 days of follow-up. In multivariable modeling, MOUD was significantly, positively associated with age (adjusted odds ratio [AOR] per year: 1.04, 95% confidence interval (CI): 1.01-1.07), hepatitis C virus (AOR = 2.15, 95% CI = 1.37-3.35), and other substance use disorders (AOR = 1.47, 95% CI = 1.05-2.04) negatively associated with alcohol use disorder (AOR = 0.70, 95% CI = 0.52-0.95), opioid prescription (AOR = 0.51, 95% CI = 0.38-0.70), and schizophrenia (AOR = 0.59, 95% CI = 0.37-0.95). MOUD was not significantly associated with mortality (adjusted hazards ratio = 1.20, 95% CI = 0.95-1.52) or new hepatic decompensation (OR = 0.57, CI = 0.30-1.09). DISCUSSION: Few Veterans with active OUD and cirrhosis received MOUD, and those with alcohol use disorder, schizophrenia, and previous prescriptions for opioids were least likely to receive these effective therapies.

Impact of Alcohol Use Disorder Treatment on Clinical Outcomes Among Patients With Cirrhosis.

BACKGROUND AND AIMS: Despite the significant medical and economic consequences of coexisting alcohol use disorder (AUD) in patients with cirrhosis, little is known about AUD treatment patterns and their impact on clinical outcomes in this population. We aimed to characterize the use of and outcomes associated with AUD treatment in patients with cirrhosis. APPROACH AND RESULTS: This retrospective cohort study included Veterans with cirrhosis who received Veterans Health Administration care and had an index diagnosis of AUD between 2011 and 2015. We assessed the baseline factors associated with AUD treatment (pharmacotherapy or behavioral therapy) and clinical outcomes for 180 days following the first AUD diagnosis code within the study time frame. Among 93,612 Veterans with cirrhosis, we identified 35,682 with AUD, after excluding 2,671 who had prior diagnoses of AUD and recent treatment. Over 180 days following the index diagnosis of AUD, 5,088 (14%) received AUD treatment, including 4,461 (12%) who received behavioral therapy alone, 159 (0.4%) who received pharmacotherapy alone, and 468 (1%) who received both behavioral therapy and pharmacotherapy. In adjusted analyses, behavioral and/or pharmacotherapy-based AUD treatment was associated with a significant reduction in incident hepatic decompensation (6.5% vs. 11.6%, adjusted odds ratio [AOR], 0.63; 95% confidence interval [CI], 0.52, 0.76), a nonsignificant decrease in short-term all-cause mortality (2.6% vs. 3.9%, AOR, 0.79; 95% CI, 0.57, 1.08), and a significant decrease in long-term all-cause mortality (51% vs. 58%, AOR, 0.87; 95% CI, 0.80, 0.96). CONCLUSIONS: Most Veterans with cirrhosis and coexisting AUD did not receive behavioral therapy or pharmacotherapy treatment for AUD over a 6-month follow-up. The reductions in hepatic decompensation and mortality suggest that future studies should focus on delivering evidence-based AUD treatments to patients with coexisting AUD and cirrhosis.

Changes in Type 2 Diabetes Medication Utilization and Costs in the United States, 2014-2019.

OBJECTIVE: The objective of this study was to describe national changes in utilization and associated costs of antidiabetic medications in the United States from 2014 to 2019, across different drug classes and insurance plans. RESEARCH DESIGN AND METHODS: This retrospective, cross-sectional study examined administrative claims from a large national pharmacy benefits manager from January 1, 2014, to December 31, 2019. Patients aged 18 years and above enrolled in commercial, Medicare, or Medicaid health plans who filled ≥1 prescription claim for an antidiabetic medication(s) during the 6-year period were included. Utilization was examined as the total number of 30-day adjusted prescription fills per user per month (PUPM). Gross costs were calculated as the sum of plan costs (net of rebates) and member out-of-pocket costs. Differences in mean utilization and costs PUPM between 2014 and 2019 for each medication class were calculated. RESULTS: The final analytic sample increased from 745,290 patients in 2014 to 1,596,006 in 2019. Antidiabetic medication utilization increased by 8.8% from 2014 to 2019, driven by increases in sodium-glucose cotransporter 2 inhibitor (48.7%; P<0.001), glucagon-like peptide 1 receptor agonist (11.8%; P<0.001), insulin (8.1%; P<0.001), and metformin (2.9%; P<0.05) utilization. Average costs PUPM rose 47.5% (P<0.001), from $126.52 in 2014 to $186.58 in 2019. Sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and combination drugs contributed significantly to these increased costs, with 6-year cost differences of 57.3%, 46.9%, and 47.2%, respectively (all P<0.001). CONCLUSION: Our study demonstrates a shift in antidiabetic medication class utilization from 2014 to 2019, where associated costs net of rebates significantly increased to a disproportionately greater extent than the significant increase in utilization PUPM.

An Interrupted Time-series Evaluation of the Association Between State Laws Mandating Prescriber Use of Prescription Drug Monitoring Programs and Discontinuation of Chronic Opioid Therapy in US Veterans.

BACKGROUND: Most states have recently passed laws requiring prescribers to use prescription drug monitoring programs (PDMPs) before prescribing opioid medications. The impact of these mandates on discontinuing chronic opioid therapy among Veterans managed in the Veterans Health Administration (VA) is unknown. We assess the association between the earliest of these laws and discontinuation of chronic opioid therapy in Veterans receiving VA health care. METHODS: We conducted a comparative interrupted time-series study in the 5 states mandating PDMP use before August 2013 (Ohio, West Virginia, Kentucky, New Mexico, and Tennessee), adjusting for trends in the 17 neighboring control states without such mandates. We modeled 25 months of prescribing for each state centered on the month the mandate became effective. We included Veterans prescribed long-term outpatient opioid therapy (305 of the preceding 365 d). Our outcomes were discontinuation of chronic opioid therapy (primary outcome) and the average daily quantity of opioids per Veteran over the following 6 months (secondary outcome). RESULTS: We included 250 monthly cohorts with 225,665 unique Veterans and 3.4 million Veteran-months. Baseline discontinuation rates before the PDMP mandates were 0.4%-2.7% per month. Kentucky saw a discontinuation increase of 1 absolute percentage point following its PDMP mandate which decreased over time. The other 4 states had no significant association between their mandates and change in opioid discontinuation. There was no evidence of decreasing opioid quantities following PDMP mandates. CONCLUSION: We did not find consistent evidence that state laws mandating provider PDMP use were associated with the discontinuation of chronic opioid therapy within the VA for the time period studied.

Impact of Marijuana Legalization on Opioid Utilization in Patients Diagnosed with Pain.

BACKGROUND: Given efforts to reduce opioid use, and because marijuana potentially offers a lower-risk alternative for treating chronic pain, there is interest in understanding the public health impact of marijuana legalization on opioid-related outcomes. OBJECTIVE: Assess the impact of recreational and medical marijuana legalization on opioid utilization among patients receiving pharmacotherapy for pain. DESIGN: Retrospective claims-based study of commercially insured patients continuously eligible for pharmacy and medical benefits from July 8, 2014 to June 30, 2017. Index pain prescription period was defined between January 8, 2015 and June 30, 2015, and longer-term opioid use examined during 2-year follow-up. Marijuana state policy on July 1, 2015, was assigned: none; medical only; or medical and recreational. PARTICIPANTS: Patients aged 18-62 without cancer diagnosis. MAIN MEASURES: Patient receiving (1) opioid at index; (2) > 7 days' supply of index opioid; (3) opioid during follow-up; and (4) ≥ 90 days' opioid supply during follow-up. Multivariable regression assessed associations between opioid utilization and state marijuana policy, adjusting for age, gender, overall disease burden, mental health treatment, concomitant use of benzodiazepine or muscle relaxant, and previous pain prescription. KEY RESULTS: Of 141,711 patients, 80,955 (57.1%) resided in states with no policy; 56,494 (39.9%) with medical-only; and 4262 (3.0%) with medical and recreational. Patients in states with both policies were more likely to receive an index opioid (aOR = 1.72, 95% CI = 1.61-1.85; aOR = 1.90, 95% CI = 1.77-2.03; P < 0.001) but less likely to receive > 7 days' index supply (aOR = 0.84, 95% CI = 0.77-0.91; aOR = 0.76, 95% CI = 0.70-0.83; P < 0.001) than patients in states with no policy or medical-only, respectively. Those in states with both policies were more likely to receive a follow-up opioid (aOR = 1.87, 95% CI = 1.71-2.05; aOR = 2.20, 95% CI = 2.01-2.42; P < 0.001) than those in states with no policy or medical-only, respectively, and more likely to receive ≥ 90 cumulative follow-up opioid days' supply (aOR = 1.18, 95% CI = 1.07-1.29; P < 0.001) than those in states with no policy. CONCLUSIONS: Our analysis does not support the supposition that access to marijuana lowers use of chronic opioids for pain.

Racial/Ethnic Differences in the Medical Treatment of Opioid Use Disorders Within the VA Healthcare System Following Non-Fatal Opioid Overdose.

BACKGROUND: After non-fatal opioid overdoses, opioid prescribing patterns are often unchanged and the use of medications for opioid use disorder (MOUDs) remains low. Whether such prescribing differs by race/ethnicity remains unknown. OBJECTIVE: To assess the association of race/ethnicity with the prescribing of opioids and MOUDs after a non-fatal opioid overdose. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients prescribed ≥ 1 opioid from July 1, 2010, to September 30, 2015, with a non-fatal opioid overdose in the Veterans Health Administration (VA). MAIN MEASURES: Primary outcomes were the proportion of patients prescribed: (1) any opioid during the 30 days before and after overdose and (2) MOUDs within 30 days after overdose by race and ethnicity. We conducted difference-in-difference analyses using multivariable regression to assess whether the change in opioid prescribing from before to after overdose differed by race/ethnicity. We also used multivariable regression to test whether MOUD prescribing after overdose differed by race/ethnicity. KEY RESULTS: Among 16,210 patients with a non-fatal opioid overdose (81.2% were white, 14.3% black, and 4.5% Hispanic), 10,745 (66.3%) patients received an opioid prescription (67.1% white, 61.7% black, and 65.9% Hispanic; p < 0.01) before overdose. After overdose, the frequency of receiving opioids was reduced by 18.3, 16.4, and 20.6 percentage points in whites, blacks, and Hispanics, respectively, with no significant difference-in-difference in opioid prescribing by race/ethnicity (p = 0.23). After overdose, 526 (3.2%) patients received MOUDs (2.9% white, 4.6% black, and 5.5% Hispanic; p < 0.01). Blacks (adjusted OR (aOR) 1.6; 95% CI 1.2, 1.9) and Hispanics (aOR 1.8; 95% CI 1.2, 2.6) had significantly larger odds of receiving MOUDs than white patients. CONCLUSIONS: In a national cohort of patients with non-fatal opioid overdose in VA, there were no racial/ethnic differences in changes in opioid prescribing after overdose. Although blacks and Hispanics were more likely than white patients to receive MOUDs in the 30 days after overdose, less than 4% of all groups received such therapy.

Value-Based Pharmaceutical Contracts: Value for Whom?

Value-based pharmaceutical contracts (VBPCs) are performance-based reimbursement agreements between healthcare payers and pharmaceutical manufacturers in which the price, amount, or nature of reimbursement is tied to value-based outcomes. VBPCs are often complex, and the nature of who benefits and in what ways can be unclear. We discuss how VBPCs compare with value-based payer-provider arrangements in terms of performance-based reimbursements and alignment of incentives. In addition, we examine how VBPCs can affect costs, clinical outcomes, and access to medications. Because these contracts are unlikely to reduce costs in isolation, we recommend taking a patient-centered approach when developing VBPCs and tying VBPCs to more overarching payer drug cost reduction strategies.

Identifying Outcome Measures for Migraine Value-Based Contracting Using the Delphi Method.

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.

Dual Receipt of Prescription Opioids From the Department of Veterans Affairs and Medicare Part D and Prescription Opioid Overdose Death Among Veterans: A Nested Case-Control Study.

Background: More than half of enrollees in the U.S. Department of Veterans Affairs (VA) are also covered by Medicare and can choose to receive their prescriptions from VA or from Medicare-participating providers. Such dual-system care may lead to unsafe opioid use if providers in these 2 systems do not coordinate care or if prescription use is not tracked between systems. Objective: To evaluate the association between dual-system opioid prescribing and death from prescription opioid overdose. Design: Nested case-control study. Setting: VA and Medicare Part D. Participants: Case and control patients were identified from all veterans enrolled in both VA and Part D who filled at least 1 opioid prescription from either system. The 215 case patients who died of a prescription opioid overdose in 2012 or 2013 were matched (up to 1:4) with 833 living control patients on the basis of date of death (that is, index date), using age, sex, race/ethnicity, disability, enrollment in Medicaid or low-income subsidies, managed care enrollment, region and rurality of residence, and a medication-based measure of comorbid conditions. Measurements: The exposure was the source of opioid prescriptions within 6 months of the index date, categorized as VA only, Part D only, or VA and Part D (that is, dual use). The outcome was unintentional or undetermined-intent death from prescription opioid overdose, identified from the National Death Index. The association between this outcome and source of opioid prescriptions was estimated using conditional logistic regression with adjustment for age, marital status, prescription drug monitoring programs, and use of other medications. Results: Among case patients, the mean age was 57.3 years (SD, 9.1), 194 (90%) were male, and 181 (84%) were non-Hispanic white. Overall, 60 case patients (28%) and 117 control patients (14%) received dual opioid prescriptions. Dual users had significantly higher odds of death from prescription opioid overdose than those who received opioids from VA only (odds ratio [OR], 3.53 [95% CI, 2.17 to 5.75]; P < 0.001) or Part D only (OR, 1.83 [CI, 1.20 to 2.77]; P = 0.005). Limitation: Data are from 2012 to 2013 and cannot capture prescriptions obtained outside the VA or Medicare Part D systems. Conclusion: Among veterans enrolled in VA and Part D, dual use of opioid prescriptions was independently associated with death from prescription opioid overdose. This risk factor for fatal overdose among veterans underscores the importance of care coordination across health care systems to improve opioid prescribing safety. Primary Funding Source: U.S. Department of Veterans Affairs.

Changes in List Prices, Net Prices, and Discounts for Branded Drugs in the US, 2007-2018.

Importance: Most studies that have examined drug prices have focused on list prices, without accounting for manufacturer rebates and other discounts, which have substantially increased in the last decade. Objective: To describe changes in list prices, net prices, and discounts for branded pharmaceutical products for which US sales are reported by publicly traded companies, and to determine the extent to which list price increases were offset by increases in discounts. Design, Setting, and Participants: Retrospective descriptive study using 2007-2018 pricing data from the investment firm SSR Health for branded products available before January 2007 with US sales reported by publicly traded companies (n = 602 drugs). Net prices were estimated by compiling company-reported sales for each product and number of units sold in the US. Exposures: Calendar year. Main Outcomes and Measures: Outcomes included list and net prices and discounts in Medicaid and other payers. List prices represent manufacturers' price to wholesalers or direct purchasers but do not account for discounts. Net prices represent revenue per unit of the product after all manufacturer concessions are accounted for (including rebates, coupon cards, and any other discount). Means of outcomes were calculated each year for the overall sample and 6 therapeutic classes, weighting each product by utilization and adjusting for inflation. Results: From 2007 to 2018, list prices increased by 159% (95% CI, 137%-181%), or 9.1% per year, while net prices increased by 60% (95% CI, 36%-84%), or 4.5% per year, with stable net prices between 2015 and 2018. Discounts increased from 40% to 76% in Medicaid and from 23% to 51% for other payers. Increases in discounts offset 62% of list price increases. There was large variability across classes. Multiple sclerosis treatments (n = 4) had the greatest increases in list (439%) and net (157%) prices. List prices of lipid-lowering agents (n = 11) increased by 278% and net prices by 95%. List prices of tumor necrosis factor inhibitors (n = 3) increased by 166% and net prices by 73%. List prices of insulins (n = 7) increased by 262%, and net prices by 51%. List prices of noninsulin antidiabetic agents (n = 10) increased by 165%, and net prices decreased by 1%. List price increases were lowest (59%) for antineoplastic agents (n = 44), but discounts only offset 41% of list price increases, leading to 35% increase in net prices. Conclusions and Relevance: In this analysis of branded drugs in the US from 2007 to 2018, mean increases in list and net prices were substantial, although discounts offset an estimated 62% of list price increases with substantial variation across classes.

Characteristics of Opioid Prescriptions to Veterans With Cirrhosis.

BACKGROUND & AIMS: Despite increased risks for adverse effects in patients with cirrhosis, little is known about opioid prescriptions for this population. We aimed to assess time trends in opioid prescribing and factors associated with receiving opioids among patients with cirrhosis. METHODS: Among Veterans with cirrhosis, identified using national Veterans Health Administration data (2005-2014), we assessed characteristics of patients and their prescriptions for opioids. We calculated the annual proportion of patients receiving any opioid prescription. Among opioid recipients, we assessed prescriptions that were long-term (>90 days' supply), for high doses (>100 MME/day), or involved combinations of opioids and acetaminophen or benzodiazepine. We evaluated patient characteristics independently associated with long-term and any opioid prescriptions using mixed-effects regression models. RESULTS: Among 127,239 Veterans with cirrhosis, 97,974 (77.0%) received a prescription for an opioid. Annual opioid prescriptions increased from 36% in 2005 to 47% in 2014 (P < .01). Among recipients of opioids, the proportions of those receiving long-term prescriptions increased from 47% in 2005 to 54% in 2014 (P < .01), and19%-21% received prescriptions for high-dose opioids. Prescriptions for combinations of opioids and acetaminophen decreased from 68% in 2005 to 50% in 2014 (P < .01) and for combinations of opioids and benzodiazepines decreased from 24% to 19% over this time (P < .01). Greater probability of long-term opioid prescriptions was independently associated with younger age, female sex, white race, hepatitis C, prior hepatic decompensation, hepatocellular carcinoma, mental health disorders, nicotine use disorders, medical comorbidities, surgery, and pain-related conditions. CONCLUSION: Among Veterans with cirrhosis, 36%-47% were prescribed opioids in each year. Mental health disorders and hepatic decompensation were independently associated with long-term opioid prescriptions.

Deprescribing in Advanced Illness: Aligning Patient, Clinician, and Health Plan Goals.

Polypharmacy has been linked to adverse outcomes including increased risk of hospitalization, falls, and death and contributes to unnecessary healthcare spending. Deprescribing efforts aim to reduce medication burden while improving or maintaining patients' quality of life. While the practice of deprescribing is gaining momentum, quality measurement and provider reimbursement are barriers that must be addressed for deprescribing to achieve widespread adoption. Because many quality measures are focused on medication use and adherence, deprescribing efforts may negatively impact primary care provider and health plan quality ratings and value-based reimbursement. In addressing this conflict, there are opportunities to proactively align the priorities and incentives of patients, providers, and plans to promote deprescribing. In this report, we propose several actionable steps to address quality and reimbursement-based barriers such as facilitating the exclusion of those engaged in deprescribing efforts from quality measures and the development of deprescribing-based quality measures.

Veteran Satisfaction with Early Experiences of Health Care Through the Veterans Choice Program: a Concurrent Mixed Methods Study.

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.

Emergency Physician Opioid Prescribing and Risk of Long-term Use in the Veterans Health Administration: an Observational Analysis.

BACKGROUND: Treatment by high-opioid prescribing physicians in the emergency department (ED) is associated with higher rates of long-term opioid use among Medicare beneficiaries. However, it is unclear if this result is true in other high-risk populations such as Veterans. OBJECTIVE: To estimate the effect of exposure to high-opioid prescribing physicians on long-term opioid use for opioid-naïve Veterans. DESIGN: Observational study using Veterans Health Administration (VA) encounter and prescription data. SETTING AND PARTICIPANTS: Veterans with an index ED visit at any VA facility in 2012 and without opioid prescriptions in the prior 6 months in the VA system ("opioid naïve"). MEASUREMENTS: We assigned patients to emergency physicians and categorized physicians into within-hospital quartiles based on their opioid prescribing rates. Our primary outcome was long-term opioid use, defined as 6 months of days supplied in the 12 months subsequent to the ED visit. We compared rates of long-term opioid use among patients treated by high versus low quartile prescribers, adjusting for patient demographic, clinical characteristics, and ED diagnoses. RESULTS: We identified 57,738 and 86,393 opioid-naïve Veterans managed by 362 and 440 low and high quartile prescribers, respectively. Patient characteristics were similar across groups. ED opioid prescribing rates varied more than threefold between the low and high quartile prescribers within hospitals (6.4% vs. 20.8%, p < 0.001). The frequency of long-term opioid use was higher among Veterans treated by high versus low quartile prescribers, though above the threshold for statistical significance (1.39% vs. 1.26%; adjusted OR 1.11, 95% CI 0.997-1.24, p = 0.056). In subgroup analyses, there were significant associations for patients with back pain (adjusted OR 1.25, 95% CI 1.01-1.55, p = 0.04) and for those with a history of depression (adjusted OR 1.28, 95% CI 1.08-1.51, p = 0.004). CONCLUSIONS: ED physician opioid prescribing varied by over 300% within facility, with a statistically non-significant increased rate of long-term use among opioid-naïve Veterans exposed to the highest intensity prescribers.

Impact of an Opioid Safety Initiative on Patients Undergoing Total Knee Arthroplasty: A Time Series Analysis.

BACKGROUND: The Opioid Safety Initiative decreased high-dose prescriptions across the Veterans Health Administration. This study sought to examine the impact of this intervention (i.e., the Opioid Safety Initiative) on pain scores and opioid prescriptions in patients undergoing total knee arthroplasty. METHODS: This was an ecological study of group-level data among 700 to 850 patients per month over 72 consecutive months (January 2010 to December 2015). The authors examined characteristics of cohorts treated before versus after rollout of the Opioid Safety Initiative (October 2013). Each month, the authors aggregated at the group-level the differences between mean postoperative and preoperative pain scores for each patient (averaged over 6-month periods), and measured proportions of patients (per 1,000) with opioid (and nonopioid) prescriptions for more than 3 months in 6-month periods, preoperatively and postoperatively. The authors compared postintervention trends versus trends forecasted based on preintervention measures. RESULTS: After the Opioid Safety Initiative, patients were slightly older and sicker, but had lower mortality rates (postintervention n = 28,509 vs. preintervention n = 31,547). Postoperative pain scores were slightly higher and the decrease in opioid use was statistically significant, i.e., 871 (95% CI, 474 to 1,268) fewer patients with chronic postoperative prescriptions. In time series analyses, mean postoperative minus preoperative pain scores had increased from 0.65 to 0.81, by 0.16 points (95% CI, 0.05 to 0.27). Proportions of patients with chronic postoperative and chronic preoperative opioid prescriptions had declined by 20% (n = 3,355 vs. expected n = 4,226) and by 13% (n = 5,861 vs. expected n = 6,724), respectively. Nonopioid analgesia had increased. Sensitivity analyses confirmed all findings. CONCLUSIONS: A system-wide initiative combining guideline dissemination with audit and feedback was effective in significantly decreasing opioid prescriptions in populations undergoing total knee arthroplasty, while minimally impacting pain scores.