Use of Single IRBs for Multi-Site Studies: A Case Report and Commentary from a National Drug Abuse Treatment Clinical Trials Network Study

Recent NIH policy stipulates that multi-site studies must use a single or IRB (Institutional Review Board) in order to streamline the review process while maintaining standards for human subjects protection. The Western States Node of the Clinical Trials Network (CTN) used a single IRB for protocol CTN-0067, a clinical trial testing the use of an opioid antagonist (extended-release naltrexone) versus opioid agonists (buprenorphine or methadone) for opioid use disorders among individuals living with HIV. This case study discusses the processes and challenges associated with use of a single IRB. These lessons are also informed by other single IRB experiences within the CTN. The intention of the NIH single IRB policy is to facilitate efficient IRB processes. Advanced planning and transparent communication, however, are critical to avoid stalling IRB approval and protocol implementation. Research teams need to account for local IRB willingness to cede to a single IRB and understand the variations in interpretations of abbreviated reviews. In order to facilitate the effective use of single IRBs, recommendations include assigning staff at each study site for IRB submission coordination and interaction with the lead site IRB staff, training investigators and key regulatory staff on expectations for working with single IRBs, dedicating a regulatory specialist at the lead site to manage the process, developing a communication plan, and supporting the development of strong working relationships with local regulatory staff and the single IRB. The CTN experiences with single IRBs may provide insights for other investigators

Use of single IRBs for multi-site studies: A case report and commentary from a National Drug Abuse Treatment Clinical Trials Network study

Recent NIH policy stipulates that multi-site studies must use a single or IRB (Institutional Review Board) in order to streamline the review process while maintaining standards for human subjects protection. The Western States Node of the Clinical Trials Network (CTN) used a single IRB for protocol CTN-0067, a clinical trial testing the use of an opioid antagonist (extended-release naltrexone) versus opioid agonists (buprenorphine or methadone) for opioid use disorders among individuals living with HIV. This case study discusses the processes and challenges associated with use of a single IRB. These lessons are also informed by other single IRB experiences within the CTN. The intention of the NIH single IRB policy is to facilitate efficient IRB processes. Advanced planning and transparent communication, however, are critical to avoid stalling IRB approval and protocol implementation. Research teams need to account for local IRB willingness to cede to a single IRB and understand the variations in interpretations of abbreviated reviews. In order to facilitate the effective use of single IRBs, recommendations include assigning staff at each study site for IRB submission coordination and interaction with the lead site IRB staff, training investigators and key regulatory staff on expectations for working with single IRBs, dedicating a regulatory specialist at the lead site to manage the process, developing a communication plan, and supporting the development of strong working relationships with local regulatory staff and the single IRB. The CTN experiences with single IRBs may provide insights for other investigators. Keywords: Institutional Review Boards, Single IRB, Clinical trial regulations, NIH IRB regulation

Long‐term outcomes after randomization to buprenorphine/naloxone versus methadone in a multi‐site trial

AIMS: To compare long-term outcomes among participants randomized to buprenorphine or methadone. DESIGN/SETTING/PARTICIPANTS: Follow-up was conducted in 2011–2014 of 1,080 opioid-dependent participants entering 7 opioid treatment programs in the USA between 2006 and 2009 and randomized (within each program) to receive open-label buprenorphine/naloxone or methadone for up to 24 weeks; 795 participants completed in-person interviews (~74% follow-up interview rate) covering on average 4.5 years. MEASUREMENTS: Outcomes were indicated by mortality and opioid use. Covariates included demographics, site, cocaine use, and treatment experiences. FINDINGS: Mortality was not different between the two randomized conditions with 23 (3.6%) of 630 participants randomized to buprenorphine having died, versus 26 (5.8%) of 450 participants randomized to methadone. Opioid use at follow-up was higher among participants randomized to buprenorphine relative to methadone (42.8% vs. 31.7% positive opioid urine specimens, p< .01, effect size (h)=0.23 [0.09, 0.38]; 5.8 days vs. 4.4 days of past 30-day heroin use, p< .05, effect size (d)=0.14 [0.00, 0.28]). Opioid use over the follow-up period by randomization condition was also significant (F(7,39600)=3.16; p < .001) mostly due to less treatment participation among participants randomized to buprenorphine than methadone. Less opioid use was associated with both buprenorphine and methadone treatment (relative to no treatment); no difference was found between the two treatments. Individuals who are white or used cocaine at baseline responded better to methadone than to buprenorphine. CONCLUSIONS: There are few differences in long-term outcomes between buprenorphine and methadone treatment for opioid dependence, and treatment with each medication is associated with a strong reduction in opioid use

Subthreshold opioid use disorder prevention (STOP) trial: a cluster randomized clinical trial: study design and methods.

BACKGROUND: Preventing progression to moderate or severe opioid use disorder (OUD) among people who exhibit risky opioid use behavior that does not meet criteria for treatment with opioid agonists or antagonists (subthreshold OUD) is poorly understood. The Subthreshold Opioid Use Disorder Prevention (STOP) Trial is designed to study the efficacy of a collaborative care intervention to reduce risky opioid use and to prevent progression to moderate or severe OUD in adult primary care patients with subthreshold OUD. METHODS: The STOP trial is a cluster randomized controlled trial, randomized at the PCP level, conducted in 5 distinct geographic sites. STOP tests the efficacy of the STOP intervention in comparison to enhanced usual care (EUC) in adult primary care patients with risky opioid use that does not meet criteria for moderate-severe OUD. The STOP intervention consists of (1) a practice-embedded nurse care manager (NCM) who provides patient participant education and supports primary care providers (PCPs) in engaging and monitoring patient-participants; (2) brief advice, delivered to patient participants by their PCP and/or prerecorded video message, about health risks of opioid misuse; and (3) up to 6 sessions of telephone health coaching to motivate and support behavior change. EUC consists of primary care treatment as usual, plus printed overdose prevention educational materials and an educational video on cancer screening. The primary outcome measure is self-reported number of days of risky (illicit or nonmedical) opioid use over 180&nbsp;days, assessed monthly via text message using items from the Addiction Severity Index and the Current Opioid Misuse Measure. Secondary outcomes assess other substance use, mental health, quality of life, and healthcare utilization as well as PCP prescribing and monitoring behaviors. A mixed effects negative binomial model with a log link will be fit to estimate the difference in means between treatment and control groups using an intent-to-treat population. DISCUSSION: Given a growing interest in interventions for the management of patients with risky opioid use, and the need for primary care-based interventions, this study potentially offers a blueprint for a feasible and effective approach to improving outcomes in this population. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT04218201, January 6, 2020

PrEP for people who use opioids: A NIDA clinical trials network survey study in Southern U.S. cities where HIV incidence is high

People who use opioids (PWUO) are at increased risk for HIV. Pre-exposure prophylaxis (PrEP) is effective but underutilized as HIV prevention among PWUO. This study examined predictors of willingness to take daily oral PrEP and long-acting injectable (LAI) PrEP among PWUO across eight Southern urban cities with high HIV incidence. HIV-negative PWUO (N = 308) seeking services in community-based programs participated in this cross-sectional survey study. Measures included demographics, sexual risk behavior, substance use frequency, and awareness of and willingness to take oral and injectable PrEP. Data were analyzed using mixed-effects models. Willingness to take daily oral and LAI PrEP was moderately high (69.16% and 62.02%, respectively). Half had heard of PrEP, but only 4% had ever taken it. Only education and condomless vaginal sex predicted willingness to take oral PrEP. Only education predicted willingness to take LAI PrEP. Polysubstance use was prevalent, with substantial proportions of PWUO reporting frequent use of injection drugs (opioids or stimulants, 79.5%), non-injection opioids (73.3%), non-injection stimulants (71.1%), cannabis (62.6%), and hazardous drinking (29.6%). About 20% reported past-year condomless anal sex, and one-third reported past-year condomless vaginal sex. PWUO in this study were amenable to PrEP, particularly in light of education and condomless vaginal sex. Careful consideration for matching PrEP messaging to the PWUO audience is needed. PrEP promotion should expand beyond men who have sex with men to include groups such as these predominantly heterosexual, polysubstance-using PWUO with HIV risk who were open to both formulations of PrEP. •Willingness for oral and long-acting injectable PrEP was moderately high in community settings.•Half of people who use opioids had heard of PrEP but few had ever taken it.•Education and condomless vaginal sex predicted willingness to take daily oral PrEP.•Education predicted willingness to take long-acting injectable PrEP.•Actively using, non-injecting PWUO are open to PrEP

HIV clinic-based extended-release naltrexone versus treatment as usual for people with HIV and opioid use disorder: a non-blinded, randomized non-inferiority trial.

BACKGROUND AND AIM: Opioid agonist medications for treatment of opioid use disorder (OUD) can improve human immunodeficiency virus (HIV) outcomes and reduce opioid use. We tested whether outpatient antagonist treatment with naltrexone could achieve similar results. DESIGN: Open-label, non-inferiority randomized trial. Setting was six US HIV primary care clinics. A total of 114 participants with untreated HIV and OUD (62% male; 56% black, 12% Hispanic; positive for fentanyl (62%), other opioids (47%) and cocaine (60%) at baseline). Enrollment halted early due to slow recruitment. INTERVENTION: HIV clinic-based extended-release naltrexone (XR-NTX; n = 55) versus treatment as usual (TAU) with buprenorphine or methadone (TAU; n = 59). MEASUREMENTS: Treatment group differences were compared for the primary outcome of viral suppression (HIV RNA ≤ 200 copies/ml) at 24 weeks and secondary outcomes included past 30-day use of opioids at 24 weeks. FINDINGS: Fewer XR-NTX participants initiated medication compared with TAU participants (47 versus 73%). The primary outcome of viral suppression was comparable for XR-NTX (52.7%) and TAU (49.2%) at 24 weeks. Non-inferiority could not be demonstrated, as the lower confidence limit of the RR did not exceed the pre-specified margin of 0.75 in intention-to-treat (ITT) analysis. The main secondary outcome of past 30-day opioid use was comparable for XR-NTX versus TAU in ITT analysis. Among those initiating medication, XR-NTX resulted in fewer days of opioid use compared with TAU in the past 30 days. CONCLUSIONS: A randomized controlled trial found supportive, but not conclusive, evidence that human immunodeficiency virus clinic-based extended-release naltrexone is not inferior to treatment as usual for facilitating human immunodeficiency virus viral suppression. Participants who initiated extended-release naltrexone used fewer opioids than those who received treatment as usual

Care Facilitation Advances Movement Along the Hepatitis C Care Continuum for Persons With Human Immunodeficiency Virus, Hepatitis C, and Substance Use: A Randomized Clinical Trial (CTN-0064)

Abstract Background Direct-acting antivirals can cure hepatitis C virus (HCV). Persons with HCV/HIV and living with substance use are disadvantaged in benefiting from advances in HCV treatment. Methods In this randomized controlled trial, participants with HCV/HIV were randomized between February 2016 and January 2017 to either care facilitation or control. Twelve-month follow-up assessments were completed in January 2018. Care facilitation group participants received motivation and strengths-based case management addressing retrieval of HCV viral load results, engagement in HCV/HIV care, and medication adherence. Control group participants received referral to HCV evaluation and an offer of assistance in making care appointments. Primary outcome was number of steps achieved along a series of 8 clinical steps (eg, receiving HCV results, initiating treatment, sustained virologic response [SVR]) of the HCV/HIV care continuum over 12 months postrandomization. Results Three hundred eighty-one individuals were screened and 113 randomized. Median age was 51 years; 58.4% of participants were male and 72.6% were Black/African American. Median HIV-1 viral load was 27 209 copies/mL, with 69% having a detectable viral load. Mean number of steps completed was statistically significantly higher in the intervention group vs controls (2.44 vs 1.68 steps; χ 2 [1] = 7.36, P = .0067). Men in the intervention group completed a statistically significantly higher number of steps than controls. Eleven participants achieved SVR with no difference by treatment group. Conclusions The care facilitation intervention increased progress along the HCV/HIV care continuum, as observed for men and not women. Study findings also highlight continued challenges to achieve individual-patient SVR and population-level HCV elimination. Clinical Trials Registration NCT02641158