Publications

2020

Lobo, Carroline P, Gerald Cochran, Chung-Chou H Chang, Walid F Gellad, Adam J Gordon, Hawre Jalal, Wei-Hsuan Lo-Ciganic, Jordan F Karp, David Kelley, and Julie M Donohue. (2020) 2020. “Associations Between the Specialty of Opioid Prescribers and Opioid Addiction, Misuse, and Overdose Outcomes.”. Pain Medicine (Malden, Mass.) 21 (9): 1871-90. https://doi.org/10.1093/pm/pnz234.

OBJECTIVE: To examine associations between opioid prescriber specialty and patient likelihood of opioid use disorder (OUD), opioid misuse, and opioid overdose.

DESIGN: Longitudinal retrospective study using Pennsylvania Medicaid data (2007-2015).

METHODS: We constructed an incident cohort of 432,110 enrollees initiating prescription opioid use without a history of OUD or overdose six months before opioid initiation. We attributed patients to one of 10 specialties using the first opioid prescriber's specialty or, alternatively, the specialty of the dominant prescriber writing the majority of the patient's opioid prescriptions. We estimated adjusted rates for OUD, misuse, and overdose, adjusting for demographic variables and medical (including pain) and psychiatric comorbidities.

RESULTS: The unadjusted incidence rates of OUD, misuse, and overdose were 7.13, 4.73, and 0.69 per 100,000 person-days, respectively. Patients initiating a new episode of opioid treatment with Pain Medicine/Anesthesiology (6.7 events, 95% confidence interval [CI] = 5.5 to 8.2) or Physical Medicine and Rehabilitation (PM&R; 6.1 events, 95% CI = 5.1 to 7.2) had higher adjusted rates for OUD per 100,000 person-days compared with Primary Care practitioners (PCPs; 4.4 events, 95% CI = 4.1 to 4.7). Patients with index prescriptions from Pain Medicine/Anesthesiology (15.9 events, 95% CI = 13.2 to 19.3) or PM&R (15.8 events, 95% CI = 13.5 to 18.4) had higher adjusted rates for misuse per 100,000 person-days compared with PCPs (9.6 events, 95% CI = 8.8 to 10.6). Findings were largely similar when patients were attributed to specialty based on dominant prescriber.

CONCLUSIONS: Differences in opioid-related risks by specialty of opioid prescriber may arise from differences in patient risk factors, provider behavior, or both. Our findings inform targeting of opioid risk mitigation strategies to specific practitioner specialties.

Pickering, Aimee N, Megan E Hamm, Alicia Dawdani, Joseph T Hanlon, Carolyn T Thorpe, Walid F Gellad, and Thomas R Radomski. (2020) 2020. “Older Patient and Caregiver Perspectives on Medication Value and Deprescribing: A Qualitative Study.”. Journal of the American Geriatrics Society 68 (4): 746-53. https://doi.org/10.1111/jgs.16370.

OBJECTIVES: Shared decision making is essential to deprescribing unnecessary or harmful medications in older adults, yet patients' and caregivers' perspectives on medication value and how this affects their willingness to discontinue a medication are poorly understood. We sought to identify the most significant factors that impact the perceived value of a medication from the perspective of patients and caregivers.

DESIGN: Qualitative study using focus groups conducted in September and October 2018.

SETTING: Participants from the Pepper Geriatric Research Registry (patients) and the Pitt+Me Registry (caregivers) maintained by the University of Pittsburgh.

PARTICIPANTS: Six focus groups of community-dwelling adults aged 65 years or older, or their caregivers, prescribed five or more medications in the preceding 12 months.

MEASUREMENTS: We sought to identify (1) general views on medication value and what makes medication worth taking; (2) how specific features such as cost or side effects impact perceived value; and (3) reactions to clinical scenarios related to deprescribing.

RESULTS: We identified four themes. Perceived effectiveness was the primary factor that caused participants to consider a medication to be of high value. Participants considered a medication to be of low value if it adversely affected quality of life. Participants also cited cost when determining value, especially if it resulted in material sacrifices. Participants valued medications prescribed by providers with whom they had good relationships rather than valuing level of training. When presented with clinical scenarios, participants ably weighed these factors when determining the value of a medication and indicated whether they would adhere to a deprescribing recommendation.

CONCLUSION: We identified that perceived effectiveness, adverse effects on quality of life, cost, and a strong relationship with the prescriber influenced patients' and caregivers' views on medication value. These findings will enable prescribers to engage older patients in shared decision making when deprescribing unnecessary medications and will allow health systems to incorporate patient-centered assessment of value into systems-based deprescribing interventions. J Am Geriatr Soc 68:746-753, 2020.

Rogal, Shari, Ada Youk, Hongwei Zhang, Walid F Gellad, Michael J Fine, Chester B Good, Maggie Chartier, et al. (2020) 2020. “Impact of Alcohol Use Disorder Treatment on Clinical Outcomes Among Patients With Cirrhosis.”. Hepatology (Baltimore, Md.) 71 (6): 2080-92. https://doi.org/10.1002/hep.31042.

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.

Ferris, Laura K, Walid F Gellad, and Inmaculada Hernandez. (2020) 2020. “Trends in List and Net Prices of Self-Administered Systemic Psoriasis Therapies Manufactured by US-Based Pharmaceutical Companies.”. JAMA Dermatology 156 (10): 1136-38. https://doi.org/10.1001/jamadermatol.2020.2685.

This economic evaluation reviews the trends in list and net price data from SSR Health for the 2007 to 2019 period of self-administered systemic psoriasis medications manufactured in the United States.

Rentsch, Christopher T, Joshua A Beckman, Laurie Tomlinson, Walid F Gellad, Charles Alcorn, Farah Kidwai-Khan, Melissa Skanderson, et al. (2020) 2020. “Early Initiation of Prophylactic Anticoagulation for Prevention of COVID-19 Mortality: A Nationwide Cohort Study of Hospitalized Patients in the United States.”. MedRxiv : The Preprint Server for Health Sciences. https://doi.org/10.1101/2020.12.09.20246579.

IMPORTANCE: Deaths among patients with coronavirus disease 2019 (COVID-19) are partially attributed to venous thromboembolism and arterial thromboses. Anticoagulants prevent thrombosis formation, possess anti-inflammatory and anti-viral properties, and may be particularly effective for treating patients with COVID-19.

OBJECTIVE: To evaluate whether initiation of prophylactic anticoagulation within 24 hours of admission is associated with decreased risk of death among patients hospitalized with COVID-19.

DESIGN: Observational cohort study.

SETTING: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, the largest integrated healthcare system in the United States.

PARTICIPANTS: All patients hospitalized with laboratory-confirmed SARS-CoV-2 infection March 1 to July 31, 2020, without a history of therapeutic anticoagulation.

EXPOSURES: Prophylactic doses of subcutaneous heparin, low-molecular-weight heparin, or direct oral anticoagulants.

MAIN OUTCOMES AND MEASURES: 30-day mortality. Secondary outcomes: inpatient mortality and initiating therapeutic anticoagulation.

RESULTS: Of 4,297 patients hospitalized with COVID-19, 3,627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3,600) received subcutaneous heparin or enoxaparin. We observed 622 deaths within 30 days of admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospitalization. In inverse probability of treatment weighted analyses, cumulative adjusted incidence of mortality at 30 days was 14.3% (95% CI 13.1-15.5) among those receiving prophylactic anticoagulation and 18.7% (95% CI 15.1-22.9) among those who did not. Compared to patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30-day mortality (HR 0.73, 95% CI 0.66-0.81). Similar associations were found for inpatient mortality and initiating therapeutic anticoagulation. Quantitative bias analysis demonstrated that results were robust to unmeasured confounding (e-value lower 95% CI 1.77). Results persisted in a number of sensitivity analyses.

CONCLUSIONS AND RELEVANCE: Early initiation of prophylactic anticoagulation among patients hospitalized with COVID-19 was associated with a decreased risk of mortality. These findings provide strong real-world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial therapy for COVID-19 patients upon hospital admission.

Hernandez, Inmaculada, and Walid F Gellad. (2020) 2020. “Differences Between Managed Care and Fee-for-Service Medicaid in the Use of Generics for High-Rebate Drugs: The Cases of Insulin Glargine and Glatiramer.”. Journal of Managed Care & Specialty Pharmacy 26 (2): 154-59. https://doi.org/10.18553/jmcp.2020.26.2.154.

BACKGROUND: Statutory rebates and preferred drug lists (PDLs) may result in differential use of biosimilars and generics between Medicaid fee-for-service (FFS) and managed care organizations (MCOs), particularly for branded drugs with large price increases subject to large inflation rebates, which are not retained by MCOs.

OBJECTIVE: To compare the use of 2 biosimilar/generics of branded drugs whose list price tripled in 2008-2018 across states with only FFS Medicaid, with MCOs not subject to statewide PDLs, with MCOs subject to statewide PDLs, and with MCOs where drug benefits have been carved out.

METHODS: Using 2018 Medicaid drug utilization data, we extracted reimbursement records in Q1-Q3 2018 for insulin glargine 100 IU/mL and glatiramer. We calculated the market share of the biosimilar insulin glargine and generic glatiramer among the corresponding drugs. We compared the market share of these products across 4 state groups: states with only FFS Medicaid, states with MCOs not subject to statewide PDLs for each drug, states with MCOs subject to PDLs, and states with MCOs where drug benefits have been carved out into FFS. We evaluated the correlation between state-level penetration of MCOs and share of biosimilar/generic products.

RESULTS: Nationally, the market share of these biosimilar/specialty generics was higher among MCOs than FFS (60.5% vs. 3.7% for biosimilar insulin glargine; 59.4% vs. 5.7% for generic glatiramer; all P < 0.001). The market share of these products was highest in states where MCOs were not subject to statewide PDLs for these drugs (59.1% for biosimilar insulin glargine, 52.8% for glatiramer) compared with states with MCOs subject to PDLs (2.4%, 18.0%); states with only FFS Medicaid (0.9%, 1.7%); or states where drug benefits have been carved out of MCOs (0.0%, 1.0%; all P < 0.001). There was a significant correlation between state-level MCO penetration and share of generic/biosimilar products (R = 0.50 for biosimilar insulin glargine and 0.57 for glatiramer; all P < 0.001).

CONCLUSIONS: For 2 drug classes with large price increases, use of biosimilars/generics was greater in MCOs than FFS Medicaid, specifically in states without PDL requirements for MCOs. These findings may reflect financial incentives for MCOs to use drugs with lower list prices because they do not benefit from statutory Medicaid rebates.

DISCLOSURES: No outside funding supported this study. Hernandez was funded by the National Heart, Lung and Blood Institute (grant number K01HL142847). The authors have nothing to disclose.

Essien, Utibe R, Jared W Magnani, Nemin Chen, Walid F Gellad, Michael J Fine, and Inmaculada Hernandez. (2020) 2020. “Race/Ethnicity and Sex-Related Differences in Direct Oral Anticoagulant Initiation in Newly Diagnosed Atrial Fibrillation: A Retrospective Study of Medicare Data.”. Journal of the National Medical Association 112 (1): 103-8. https://doi.org/10.1016/j.jnma.2019.10.003.

BACKGROUND: Atrial fibrillation (AF) is the most common heart rhythm disorder and is associated with a 5-fold increased risk of ischemic stroke. Racial/ethnic minorities and women with AF have higher rates of stroke compared to white individuals and men respectively. Oral anticoagulation reduces the risk of stroke, yet prior research has described racial/ethnic and sex-based variation in its use. We sought to examine the initiation of any oral anticoagulant (warfarin or direct-acting oral anticoagulants, DOACs) by race/ethnicity and sex in patients with incident, non-valvular AF. Further in those who initiated any anticoagulant, we examined DOAC vs. warfarin initiation by race/ethnicity and sex.

METHODS: We used claims data from a 5% sample of Medicare beneficiaries to identify patients with incident AF from 2012 to 2014, excluding those without continuous Medicare enrollment. We used logistic regression to assess the association between race/ethnicity (white, black, Hispanic), sex, and oral anticoagulant initiation (any, warfarin vs. DOAC), adjusting for sociodemographics, medical comorbidities, stroke and bleeding risk.

RESULTS: The cohort of 42,952 patients with AF included 17,935 women, 3282 blacks, and 1958 Hispanics. Overall OAC initiation was low (49.2% whites, 48.1% blacks, 47.5% Hispanics, 48.1% men, and 51.5% women). After adjusting, blacks (odds ratio (OR) 0.84; 95% CI, 0.78-0.91) were less likely than whites to initiate any oral anticoagulant with no difference observed between Hispanics and whites (OR 0.92; 95% CI, 0.83-1.01). Women were less likely than men to initiate any oral anticoagulant, OR 0.59 (95% CI 0.55-0.64). Among initiators of oral anticoagulation, DOAC use was low (35.8% whites, 29.3% blacks, 40.0% Hispanics, 41.6% men, and 42.4% women). After adjusting, blacks were less likely to initiate DOACs than whites, OR 0.75 (95% CI 0.66-0.85); the odds of DOAC initiation did not differ between Hispanic and white patients or between men and women.

CONCLUSION: In a national cohort of Medicare beneficiaries with newly-diagnosed AF, overall oral anticoagulant initiation was lower in blacks and women, with no difference observed by Hispanic ethnicity. Among oral anticoagulant initiators, blacks were less likely to initiate novel DOACs, with no differences identified by Hispanic ethnicity or sex. Identifying modifiable causes of treatment disparities is needed to improve quality of care for all patients with AF.

Lipkin, Jacob S, Joshua M Thorpe, Walid F Gellad, Joseph T Hanlon, Xinhua Zhao, Carolyn T Thorpe, Florentina E Sileanu, et al. (2020) 2020. “Identifying Sociodemographic Profiles of Veterans at Risk for High-Dose Opioid Prescribing Using Classification and Regression Trees.”. Journal of Opioid Management 16 (6): 409-24. https://doi.org/10.5055/jom.2020.0599.

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.