Faculty Bibliography

BACKGROUND: Buprenorphine maintenance for opioid dependence remains of limited availability among underserved populations, despite increases in US opioid misuse and overdose deaths. Low threshold primary care treatment models including the use of unobserved, "home," buprenorphine induction may simplify initiation of care and improve access. Unobserved induction and long-term treatment outcomes have not been reported recently among large, naturalistic cohorts treated in low threshold safety net primary care settings. METHODS: This prospective clinical registry cohort design estimated rates of induction-related adverse events, treatment retention, and urine opioid results for opioid dependent adults offered buprenorphine maintenance in a New York City public hospital primary care office-based practice from 2006 to 2013. This clinic relied on typical ambulatory care individual provider-patient visits, prescribed unobserved induction exclusively, saw patients no more than weekly, and did not require additional psychosocial treatment. Unobserved induction consisted of an in-person screening and diagnostic visit followed by a 1-week buprenorphine written prescription, with pamphlet, and telephone support. Primary outcomes analyzed were rates of induction-related adverse events (AE), week 1 drop-out, and long-term treatment retention. Factors associated with treatment retention were examined using a Cox proportional hazard model among inductions and all patients. Secondary outcomes included overall clinic retention, buprenorphine dosages, and urine sample results. RESULTS: Of the 485 total patients in our registry, 306 were inducted, and 179 were transfers already on buprenorphine. Post-induction (n = 306), week 1 drop-out was 17%. Rates of any induction-related AE were 12%; serious adverse events, 0%; precipitated withdrawal, 3%; prolonged withdrawal, 4%. Treatment retention was a median 38 weeks (range 0-320) for inductions, compared to 110 (0-354) weeks for transfers and 57 for the entire clinic population. Older age, later years of first clinic visit (vs. 2006-2007), and baseline heroin abstinence were associated with increased treatment retention overall. CONCLUSIONS: Unobserved "home" buprenorphine induction in a public sector primary care setting appeared a feasible and safe clinical practice. Post-induction treatment retention of a median 38 weeks was in line with previous naturalistic studies of real-world office-based opioid treatment. Low threshold treatment protocols, as compared to national guidelines, may compliment recently increased prescriber patient limits and expand access to buprenorphine among public sector opioid use disorder patients.

We examine ethical challenges encountered in the design of an effectiveness trial (CTN-0051; X:BOT), comparing sublingual buprenorphine-naloxone (BUP-NX), an established treatment for opioid dependence, to the newer extended-release injectable naltrexone (XR-NTX). Ethical issues surrounded: 1) known poor effectiveness of one possible, commonly used treatment as usual control condition-detoxification followed by counseling without medication; 2) the role of patients' preferences for treatments, given that treatments were clinically approved and available to the population; 3) differences between the optimal "usual treatment" clinical settings for different treatments making it challenging to design a fair comparison; 4) vested interest groups favoring different treatments exerting potential influence on the design process; 5) potentially vulnerable populations of substance users and prisoners; 6) potential therapeutic misconception in the implementation of safety procedures; and 7) high cost of a large trial limiting questions that could be addressed. We examine how the design features underlying these ethical issues are characteristic of effectiveness trials, which are often large trials that compare treatments with varying degrees of existing effectiveness data and familiarity to patients and clinicians, in community-based treatment settings, with minimal exclusion criteria that could involve vulnerable populations. Hence, investigators designing effectiveness trials may wish to remain alert to the possibility of similar ethical issues.

The acceptability and clinical impact of a web-based intervention among patients entering addiction treatment who lack recent internet access are unclear. This secondary analysis of a national multisite treatment study (NIDA Clinical Trials Network-0044) assessed for acceptability and clinical impact of a web-based psychosocial intervention among participants enrolling in community-based, outpatient addiction treatment programs. Participants were randomly assigned to 12 weeks of a web-based therapeutic education system (TES) based on the community reinforcement approach plus contingency management versus treatment as usual (TAU). Demographic and clinical characteristics, and treatment outcomes were compared among participants with recent internet access in the 90 days preceding enrollment (N = 374) and without internet access (N = 133). Primary outcome variables included (1) acceptability of TES (i.e., module completion; acceptability of web-based intervention) and (2) clinical impact (i.e., self-reported abstinence confirmed by urine drug/breath alcohol tests; retention measured as time to dropout). Internet use was common (74 %) and was more likely among younger (18-49 years old) participants and those who completed high school (p < .001). Participants randomized to TES (n = 255) without baseline internet access rated the acceptability of TES modules significantly higher than those with internet access (t = 2.49, df = 218, p = .01). There was a near significant interaction between treatment, baseline abstinence, and internet access on time to dropout (chi 2(1) = 3.8089, p = .051). TES was associated with better retention among participants not abstinent at baseline who had internet access (X 2(1) = 6.69, p = .01). These findings demonstrate high acceptability of this web-based intervention among participants that lacked recent internet access.

INTRODUCTION: For opioid-dependent patients in the US and elsewhere, detoxification and counseling-only aftercare are treatment mainstays.Long-term abstinence is rarely achieved; many patients relapse and overdose after detoxification.Methadone, buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) can prevent opioid relapse but are underutilized.This study is intended to develop an evidence-base to help patients and providers make informed choices and to foster wider adoption of relapse-prevention pharmacotherapies. METHODS: The National Institute on Drug Abuse's Clinical Trials Network (CTN) study CTN-0051, X:BOT, is a comparative effectiveness study of treatment for 24weeks with XR-NTX, an opioid antagonist, versus BUP-NX, a high affinity partial opioid agonist, for opioid dependent patients initiating treatment at 8 short-term residential (detoxification) units and continuing care as outpatients.Up to 600 participants are randomized (1:1) to XR-NTX or BUP-NX. RESULTS: The primary outcome is time to opioid relapse (i.e., loss of persistent abstinence) across the 24-week treatment phase.Differences between arms in the distribution of time-to-relapse will be compared (construction of the asymptotic 95% CI for the hazard ratio of the difference between arms).Secondary outcomes include proportions retained in treatment, rates of opioid abstinence, adverse events, cigarette, alcohol, and other drug use, and HIV risk behaviors; opioid cravings, quality of life, cognitive function, genetic moderators, and cost effectiveness. CONCLUSIONS: XR-NTX and BUP-NX differ considerably in their characteristics and clinical management; no studies to date have compared XR-NTX with buprenorphine maintenance.Study design choices and compromises inherent to a comparative effectiveness trial of distinct treatment regimens are reviewed. CLINICAL TRIAL REGISTRATION: NCT02032433.

The deployment of health information technologies promises to optimize clinical outcomes for populations with substance use disorders. Electronic health records, web-based counseling interventions, and mobile phone applications enhance the delivery of evidence-based behavioral and pharmacological treatments, with minimal burden to clinical personnel, infrastructure, and work flows. This clinical case shares a recent experience utilizing mobile phone text messaging between an office-based buprenorphine provider in a safety net ambulatory clinic and a patient seeking buprenorphine treatment for opioid use disorder. The case highlights the use of text message-based physician-patient communication to facilitate unobserved "home" induction onto buprenorphine.

BACKGROUND: Extended-release naltrexone (XR-NTX) is an injectable monthly sustained-release mu opioid receptor antagonist, which blocks the typical effects of heroin and other opioid agonists. Use of XR-NTX among opioid dependent persons leaving jails and prisons is increasing despite scant high-quality evidence regarding XR-NTX's effectiveness at re-entry. METHODS: This 24-week, open-label randomized controlled trial examines the effectiveness of XR-NTX as opioid relapse prevention at release from jail (N=85) compared to enhanced treatment as usual (ETAU, N=85). A third, non-randomized, quasi-experimental naturalistic arm of participants who have newly initiated a jail-to-community methadone treatment program (MTP, N=85) allows for comparisons to a methadone standard-of-care. RESULTS: We describe the rationale, design, and primary and secondary outcomes of the study. The primary outcome is an opioid relapse event; the primary contrast is a time-to-relapse comparison of XR-NTX and ETAU over a 24-week treatment phase. Secondary outcomes are rates of: (a) post-release opioid treatment participation, (b) opioid, alcohol, and cocaine use, (c) injection drug use and HIV sexual risk behaviors, (d) overdose (fatal and non-fatal) and all-cause mortality, and, (e) re-incarceration. CONCLUSIONS: XR-NTX is a potentially important, effective treatment and relapse prevention option for a large US population of persons with opioid use disorders leaving jails. This study will estimate XR-NTX's effectiveness relative to existing standards of care, including counseling-only treatment-as-usual and methadone maintenance.

BACKGROUND: Among the nearly 750,000 inmates in U.S. jails, 12% report using opioids regularly, 8% report use in the month prior to their offense, and 4% report use at the time of their offense. Although ample evidence exists that medications effectively treat Opiate Use Disorder (OUD) in the community, strong evidence is lacking in jail settings. The general lack of medications for OUD in jail settings may place persons suffering from OUD at high risk for relapse to drug use and overdose following release from jail. METHODS: The three study sites in this collaborative are pooling data for secondary analyses from three open-label randomized effectiveness trials comparing: (1) the initiation of extended-release naltrexone [XR-NTX] in Sites 1 and 2 and interim methadone in Site 3 with enhanced treatment-as usual (ETAU); (2) the additional benefit of patient navigation plus medications at Sites 2 and 3 vs. medication alone vs. ETAU. Participants are adults with OUD incarcerated in jail and transitioning to the community. RESULTS: We describe the rationale, specific aims, and designs of three separate studies harmonized to enhance their scientific yield to investigate how to best prevent jail inmates from relapsing to opioid use and associated problems as they transition back to the community. CONCLUSIONS: Conducting drug abuse research during incarceration is challenging and study designs with data harmonization across different sites can increase the potential value of research to develop effective treatments for individuals in jail with OUD.