Faculty Bibliography

Background/UNASSIGNED:The extent to which clinical trials of medications for opioid use disorder (MOUD) are representative or not is unknown. Some patient characteristics modify MOUD effectiveness; if these same characteristics differ in distribution between the trial population and usual-care population, this could contribute to lack of generalizability-a discrepancy between trial and usual-care effectiveness. Our objective was to identify interpretable, multidimensional subgroups who were prescribed MOUD in substance use treatment programs in the US but who were not represented or under-represented by clinical trial participants. Methods/UNASSIGNED:This was a secondary descriptive analysis of trial and real-world data. The trial data included twenty-seven US opioid treatment programs in the National Drug Abuse Treatment Clinical Trials Network, N = 2,199 patients. The real-world data included US substance use treatment programs that receive public funding, N = 740,015 patients. We characterized real-world patient populations who were non-represented and under-represented in the trial data in terms of sociodemographic and clinical characteristics that could modify MOUD effectiveness. Results/UNASSIGNED:We found that 10.7% of MOUD patients in TEDS-A were not represented in the three clinical trials. As expected, pregnant MOUD patients (n = 19,490) were not represented. Excluding pregnancy, education and marital status from the characteristics, 2.6% of MOUD patients were not represented. Patients aged 65 years and older (n = 11,204), and those 50-64 years who identified as other (non-White, non-Black, and non-Hispanic) race/ethnicity or multi-racial (n = 7,281) were under-represented. Conclusions/UNASSIGNED:Quantifying and characterizing non- or under-represented subgroups in trials can provide the data necessary to improve representation in future trials and address research-to-practice gaps.

BACKGROUND:Although there is consensus that having a "high-enough" dose of buprenorphine (BUP-NX) or methadone is important for reducing relapse to opioid use, there is debate about what this dose is and how it should be attained. We estimated the extent to which different dosing strategies would affect risk of relapse over 12 weeks of treatment, separately for BUP-NX and methadone. METHODS:This was a secondary analysis of three comparative effectiveness trials. We examined four dosing strategies: 1) increasing dose in response to participant-specific opioid use, 2) increasing dose weekly until some minimum dose (16 mg BUP, 100 mg methadone) was reached, 3) increasing dose weekly until some minimum and increasing dose in response to opioid use thereafter (referred to as the "hybrid strategy"), and 4) keeping dose constant after the first 2 weeks of treatment. We used a longitudinal sequentially doubly robust estimator to estimate contrasts between dosing strategies on risk of relapse. RESULTS:For BUP-NX, increasing dose following the hybrid strategy resulted in the lowest risk of relapse. For methadone, holding dose constant resulted in greatest risk of relapse; the other three strategies performed similarly. For example, the hybrid strategy reduced week 12 relapse risk by 13 % (RR: 0.87, 95 %CI: 0.83-0.95) and by 20 % (RR: 0.80, 95 %CI: 0.71-0.90) for BUP-NX and methadone respectively, as compared to holding dose constant. CONCLUSIONS:Doses should be targeted toward minimum thresholds and, in the case of BUP-NX, raised when patients continue to use opioids.

BACKGROUND AND AIMS/OBJECTIVE:Dynamic, adaptive pharmacologic treatment for opioid use disorder (OUD) has been previously recommended over static dosing to prevent relapse, and is aligned with personalized medicine. However, there has been no quantitative evidence demonstrating its advantage. Our objective was to estimate the extent to which a hypothetical intervention that increased buprenorphine dose in response to opioid use would affect risk of relapse over 24 weeks of follow-up. DESIGN/METHODS:A secondary analysis of the buprenorphine arm of an open-label randomized controlled 24-week comparative effectiveness trial, 2014-17. SETTING/METHODS:Eight community addiction treatment programs in the United States. PARTICIPANTS/METHODS:English-speaking adults with DSM-5 OUD, recruited during inpatient admission (n = 270). Participants were mainly white (65%) and male (72%). INTERVENTION(S)/METHODS:Participants were treated with daily sublingual buprenorphine-naloxone (BUP-NX), with dose based on clinical indication, determined by the provider. We examined a hypothetical intervention of increasing dose in response to opioid use. MEASUREMENTS/METHODS:Outcome was relapse to regular opioid use during the 24 weeks of outpatient treatment, assessed in a survival framework. We estimated the relapse-free survival curves of participants under a hypothetical (i.e. counterfactual) intervention in which their BUP-NX dosage would be increased following their own subject-specific opioid use during the first 12 weeks of treatment versus a hypothetical intervention in which dose would remain constant. FINDINGS/RESULTS:We estimated that increasing BUP-NX dose in response to recent opioid use would lower risk of relapse by 19.17 percentage points [95% confidence interval (CI) = -32.17, -6.18) (additive risk)] and 32% (0.68, 95% CI = 0.49, 0.86) (relative risk). The number-needed-to-treat with this intervention to prevent a single relapse is 6. CONCLUSIONS:In people with opioid use disorder, a hypothetical intervention that increases sublingual buprenorphine-naloxone dose in response to opioid use during the first 12 weeks of treatment appears to reduce risk of relapse over 24 weeks, compared with holding the dose constant after week 2.

In response to the opioid crisis in New York State (NYS), the Unified Court System developed a new treatment court model-the opioid intervention court-designed around 10 Essential Elements of practice to address the flaws of existing drug courts in handling those with opioid addiction via broader inclusion criteria, rapid screening, and linkage to medications to treat opioid use disorder (MOUD). The new court model is now being rolled out statewide yet, given the innovation of the opioid court, the exact barriers to implementation in different counties with a range of resources are largely unknown. We describe a study protocol for the development and efficacy-test of a new implementation intervention (Opioid Court REACH; Research on Evidence-Based Approaches to Court Health) that will allow the opioid court, as framed by the 10 Essential Elements, to be scaled-up across 10 counties in NYS. Using a cluster-randomized stepped-wedge type-2 hybrid effectiveness-implementation design, we will test: (a) the implementation impact of Opioid Court REACH in improving implementation outcomes along the opioid cascade of care (screening, referral, treatment enrollment, MOUD initiation), and (b) the clinical and cost effectiveness of Opioid Court REACH in improving public health (treatment retention/court graduation) and public safety (recidivism) outcomes. Opioid Court REACH has the potential to improve management of individuals with opioid addiction in the court system via widespread scale-up of the opioid court model across the U.S., should this study find it to be effective.

BACKGROUND:Mental health issues in individuals with substance use disorders are common and can affect treatment outcomes. OBJECTIVES:Secondary analysis of a multi-center trial of an internet-delivered psychosocial SUD treatment intervention (Therapeutic Education System; TES) to: 1) describe psychological symptoms over time, 2) explore whether treatment assignment was associated with psychological symptoms 3) explore whether psychological symptoms at baseline moderated the effect of TES on abstinence or retention at the end of treatment. METHODS:Psychological symptoms were measured using the Global Severity Index (GSI) from the Brief Symptom Inventory (BSI-18), PHQ-9, and MINI SPIN (social anxiety). Zero-inflated-negative-binomial models given high numbers of "0" GSI scores and multivariate logistic regression models were run to estimate the effect of the interaction between treatment and baseline psychological symptoms. RESULTS: = 0.0482). CONCLUSIONS:Psychological symptoms may improve over time in individuals seeking treatment for SUD, and for those with social anxiety, technology-based treatments may result in a better response. Examining the effect of SUD treatment on broader psychological outcomes in addition to abstinence may help clinicians provide more individualized care for those with co-occurring conditions.

The temporary loosening of regulations governing methadone and buprenorphine treatment for opioid use disorder (OUD) in the U.S., instituted to prevent the spread of COVID-19, has created an opportunity to explore the effectiveness of new models of care for people with OUD. The opioid cascade describes the current status of the treatment system, where only a fraction of people with OUD initiate effective medication treatment for OUD (MOUD), and of those only a fraction is retained in treatment. Regulatory changes-such as availability of larger take-home supplies of methadone and buprenorphine initiated via telemedicine (e.g., no initial in person visit; telemedicine buprenorphine permitted across state lines)-could modify the cascade, by reducing the burden and increasing the attractiveness, availability, and feasibility of MOUD both for people with OUD and for providers. We review examples of more liberal MOUD regimens, including the implementation of buprenorphine in France in the 1990s, primary care-based methadone in Canada, and low-threshold buprenorphine models. Research is needed to document whether new models implemented in the U.S. in the wake of COVID-19 are successful, and whether safety concerns, such as diversion and misuse, emerge. We discuss barriers to implementation, including racial and ethnic health disparities, and lack of knowledge and reluctance among potential providers of MOUD. We suggest that the urgency and public spiritedness of the response to COVID-19 be harnessed to make gains on the opioid cascade, inspiring prescribers, health systems, and communities to embrace the delivery of MOUD to meet the needs of an increasingly vulnerable population.