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IIR 14-297 – HSR&D Study

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IIR 14-297
Safety of Opioid use Among Veterans Receiving Care in Multiple Health Systems
Walid F. Gellad MD MPH
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
Pittsburgh, PA
Funding Period: February 2015 - September 2018

Almost 25% of VA patients receive opioid medications as a key component of pain management. VA has adopted several strategies to mitigate the risks of opioid-related adverse events, but these efforts focus almost entirely on monitoring prescriptions dispensed within VA. Many Veterans have other forms of health insurance and can access healthcare and prescriptions in non-VA settings. The VA cannot fully understand the safety of opioid prescribing to Veterans, or develop successful interventions to address opioid safety, without understanding this non-VA care. Our project will address this critical knowledge gap.

Our aims are to describe the patterns of opioid use from VA and non-VA sources among Veterans receiving care in the VA, evaluate the impact of dual use of VA and non-VA opioid medications on opioid safety and opioid related serious adverse events, and explore provider and other stakeholder perspectives on identifying and managing dual use of opioid medications in Veterans.

This mixed methods study consists of 2 quantitative aims (Aims 1-2) and 1 qualitative aim (Aim 3), that will be conducted in parallel. The quantitative aims will assess patterns of opioid use and the relationship between dual use of opioid medications from VA and non-VA data sources and opioid safety and opioid-related adverse events. To accomplish these aims, we will analyze linked administrative data files from VA and non-VA data sources to track medication use and health care utilization for all Veterans receiving an opioid medication. The analyses will utilize propensity scores and instrumental variables, along with multiple mediation path analyses. The qualitative aim will complement Aims 1-2 with 2 phases of semi-structured interviews of key stakeholders, exploring: (1) provider perceptions of dual use of opioid medications and (2) the views of stakeholder leaders in VA and outside VA to help interpret and synthesize the quantitative and qualitative results about dual use of opioid medications.

We estimated the prevalence and consequences of receiving prescription opioids from both VA and Medicare Part D. This analysis is published in the American Journal of Public Health (Am J Public Health. 2017 Dec 21:e1-e8. doi: 10.2105/AJPH.2017.304174. [Epub ahead of print]). Overall, 135,643 (25.1%) Veterans received opioids from VA only, 332,630 (61.7%) from Part D only, and 71,200 (13.2%) from both. The dual use group was more likely than the VA-only group to receive >100 morphine milligram equivalent (MME) for >1 day (34.3% vs. 10.9%, adjusted risk ratio (aRR) 3.0, 95%CI 2.9-3.1), have more days with >100 MME (42.5 vs. 16.9 days, adjusted difference 16.4 days, 95%CI 15.7-17.2) and receive >120 MME for 90 consecutive days (7.8% vs. 3.1%, aRR 2.2, 95%CI 2.1-2.3).

Additionally, we evaluated VA physicians' perspectives and experiences regarding use of Prescription Drug Monitoring Programs (PDMPs) to monitor Veterans' opioid use from non-VA sources. This analysis is published in the Journal of General Internal Medicine (JGIM online, March 8, 2018. We identified 3 overarching themes. First, physicians universally supported PDMPs (MA, IL) or desired access to one (PA), despite noting additional time and administrative burdens associated with their use. To improve use, physicians suggested: 1) linking PDMPs with the VA electronic health record; 2) using templated notes to document PDMP use; and 3) delegating routine PDMP queries to ancillary staff. Second, PDMP use challenged physicians' underlying biases regarding opioid misuse. JGIM, published online, 08 March 2018.

We studied overlapping buprenorphine, opioid, and benzodiazepine
prescriptions among dual system users. This analysis is published in Substance Abuse (Subst Abus. 2017 ; 38(1): 22-25.). We identified 1,790 dually enrolled Veterans with buprenorphine prescriptions, including 760 (43%) from VA and 1,091 (61%) from Part D (61 Veterans with buprenorphine from both systems were included in each group). Among VA buprenorphine recipients, 199 (26%)
received an overlapping opioid prescription and 11 (1%) received an overlapping benzodiazepine prescription from Part D. Among Part D buprenorphine recipients, 208 (19%) received an overlapping opioid prescription and 178 (16%) received an overlapping benzodiazepine prescription from VA. Among VA and Part D buprenorphine recipients with cross-system opioid overlap, 25% (49/199) and 35% (72/208), respectively, had >90 days of overlap.

We are also examined prescription opioid/benzodiazepine overlap among dual system users. This analysis was published in Annals of Internal Medicine (published at on 9 October 2018). Of 368 891 eligible veterans, 18.3% received prescriptions from the VA only, 30.3% from Medicare only, and 51.4% from both VA and Medicare. The proportion with PQA opioid- benzodiazepine overlap was larger for the dual use group than the VA-only group (23.1% vs. 17.3%; adjusted risk ratio [aRR], 1.27 [95% CI, 1.24 to 1.30]) and Medicare-only group (23.1% vs. 16.5%; aRR, 1.12 [CI, 1.10 to 1.14]). The proportion with high-dose overlap was also larger for the dual-use group than the VA-only group (4.7% vs. 2.3%; aRR, 2.23 [CI, 2.10 to 2.36]) and Medicare-only group (4.7% vs. 2.9%; aRR, 1.06 [CI, 1.02 to 1.11]).

We studied drug-based comorbidity adjustment to use in studies of dual use. Abstract was submitted to SGIM 2017 and Academy Health 2017. Paper was published online at JGIM. Controlling for Elixhauser comorbidities, dual-use groups 2-4 had significantly decreased odds of death or hospitalization compared to VA-predominant users. Controlling for RxRisk-V comorbidities, groups 2-4 had increased odds of death compared to VA predominant users, but variable odds of hospitalization, with group 2 having increased odds (OR 1.06, CI 1.04-1.09), while groups 3 (OR 0.96, CI 0.94-0.99) and 4 (OR 0.93, CI 0.89-0.97) had decreased odds.

We also examined prescription opioid supply preceding death in individuals dying from unintentional prescription opioid overdoses and described the characteristics of these individuals, particularly among Veterans. Published online at Research and Social and Administrative Pharmacy. Among 1,181 decedents, 643 (54.4%) had prescription opioid supply on the day of death, and 735 (62.2%) within 30 days based on linked data, compared to 40.1% and 46.7%, respectively, using VA data alone. Decedents with prescription opioid supply were significantly older and less likely to have alcohol or illicit drugs as co-occurring substances involved in the overdose. Using linked data, 241 (20.4%) decedents lacked prescription opioid supply within a year of death.

We evaluated the association between dual system opioid prescribing and prescription opioid overdose death using a nested case-control design. Paper is under review. Among cases, mean age (SD) was 57.3 (9.1) years, 194 (90%) were male, and 181 (85%) non-Hispanic White. Overall, 60 (28%) cases and 117 (14%) controls received dual opioid prescriptions. Veterans with dual use had significantly higher odds of prescription opioid overdose death than those who received opioids from VA (OR 3.53, 95% CI 2.17-5.75, P <0.001) or Part D only (OR 1.83, 95% CI 1.20-
74 2.77, P=0.005).

We studied the extent to which variation in individual ED physicians' opioid prescribing was associated with long-term opioid use in Veterans. Paper is under review. 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 3-fold 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 vs. low-quartile prescribers (1.39% vs. 1.26%; adjusted OR 1.11, 95% CI 1.00-1.24, p=0.048), with similar results across specific ED diagnoses.

We are also examining intersecting socio-demographic characteristics that influence risk of high-dose opioid prescribing, opioid de-prescribing and disparities in medication assisted treatment after overdose.

1. So far, this study has produced 12 research papers including several in high impact journals.

2. This study has generated 17 abstracts accepted for presentations (including several oral presentations).

3. This study has further adapted a medication-based comorbidity measure, specifically developed for research in dual use, that is not susceptible to coding discrepancies that exist between VA and Medicare that limit use of ICD-9/10 based comorbidity measures.

4. These results have lead to developing a data sharing agreement between VA and CMS that will soon be signed and have direct positive benefits for Veteran health and quality of care.


Journal Articles

  1. Moyo P, Zhao X, Thorpe CT, Thorpe JM, Sileanu FE, Cashy JP, Hale JA, Mor MK, Radomski TR, Donohue JM, Hausmann LRM, Hanlon JT, Good CB, Fine MJ, Gellad WF. Patterns of opioid prescriptions received prior to unintentional prescription opioid overdose death among Veterans. Research in social & administrative pharmacy : RSAP. 2018 Oct 17.
  2. Carico R, Zhao X, Thorpe CT, Thorpe JM, Sileanu FE, Cashy JP, Hale JA, Mor MK, Radomski TR, Hausmann LRM, Donohue JM, Suda KJ, Stroupe K, Hanlon JT, Good CB, Fine MJ, Gellad WF. Receipt of Overlapping Opioid and Benzodiazepine Prescriptions Among Veterans Dually Enrolled in Medicare Part D and the Department of Veterans Affairs: A Cross-sectional Study. Annals of internal medicine. 2018 Nov 6; 169(9):593-601.
  3. Radomski TR, Bixler FR, Zickmund SL, Roman KM, Thorpe CT, Hale JA, Sileanu FE, Hausmann LRM, Thorpe JM, Suda KJ, Stroupe KT, Gordon AJ, Good CB, Fine MJ, Gellad WF. Physicians' Perspectives Regarding Prescription Drug Monitoring Program Use Within the Department of Veterans Affairs: a Multi-State Qualitative Study. Journal of general internal medicine. 2018 Aug 1; 33(8):1253-1259.
  4. Gellad WF, Thorpe JM, Zhao X, Thorpe CT, Sileanu FE, Cashy JP, Hale JA, Mor MK, Radomski TR, Hausmann LRM, Donohue JM, Gordon AJ, Suda KJ, Stroupe KT, Hanlon JT, Cunningham FE, Good CB, Fine MJ. Impact of Dual Use of Department of Veterans Affairs and Medicare Part D Drug Benefits on Potentially Unsafe Opioid Use. American journal of public health. 2018 Feb 1; 108(2):248-255.
  5. Radomski TR, Zhao X, Thorpe CT, Thorpe JM, Naples JG, Mor MK, Good CB, Fine MJ, Gellad WF. The Impact of Medication-Based Risk Adjustment on the Association Between Veteran Health Outcomes and Dual Health System Use. Journal of general internal medicine. 2017 Sep 1; 32(9):967-973.
  6. Gellad WF, Zhao X, Thorpe CT, Thorpe JM, Sileanu FE, Cashy JP, Mor M, Hale JA, Radomski T, Hausmann LR, Fine MJ, Good CB. Overlapping buprenorphine, opioid, and benzodiazepine prescriptions among veterans dually enrolled in Department of Veterans Affairs and Medicare Part D. Substance Abuse. 2017 Jan 1; 38(1):22-25.
Journal Other

  1. Roberts AW, Gellad WF, Skinner AC. Lock-In Programs and the Opioid Epidemic: A Call for Evidence. [Editorial]. American journal of public health. 2016 Nov 1; 106(11):1918-1919.
  2. Gellad WF. The Veterans Choice Act and Dual Health System Use. Journal of general internal medicine. 2016 Feb 1; 31(2):153-4.
HSR&D or QUERI Articles

  1. Gellad WF. Opioids and Dual Healthcare System Use. HSR&D Forum. 2016 May 31.
VA Cyberseminars

  1. Gellad WF. Examining Veterans' Pharmacy Use With VA and Medicare Pharmacy Data. [Cyberseminar]. 2016 Feb 1.
Government Briefings

  1. Gellad WF. University of Pittsburgh Efforts to Address the Opioid Epidemic: Briefing before the Assistant Secretary for Financial Resources, United States Department of Health and Human Services; 2016 Aug 9; Pittsburgh, PA.
Conference Presentations

  1. Radomski TR, Zhao X, Thorpe CT, Thorpe JM, Good CB, Mor M, Fine MJ, Gellad WF. Is Dual Use of VA and Medicare Diabetes Services Associated with Adverse Health Outcomes? Poster session presented at: Society of General Internal Medicine Annual Meeting; 2016 May 12; Hollywood, FL.

DRA: Health Systems, Other Conditions
DRE: Treatment - Observational
Keywords: Adverse Event Monitoring, Patient Safety
MeSH Terms: none