Opioid use disorder continues to be a significant problem in the United States and worldwide. Three medications-methadone, buprenorphine, and extended-release injectable naltrexone,- are efficacious ...for treating opioid use disorder (OUD). However, the utility of these medications is limited, in part due to poor rates of retention in treatment. In addition, minimum recovery milestones and other factors that influence when and whether individuals can safely discontinue medications are unknown. The National Drug Abuse Treatment Clinical Trials Network (CTN) study "Optimizing Retention, Duration, and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy" (RDD; CTN-0100) will be among the largest clinical trials on treatment of OUD yet conducted, consisting of two phases, the Retention phase, and the Duration-Discontinuation phase. The Retention phase, open to patients initiating treatment, will test different doses and formulations of buprenorphine (standard dose sublingual, high dose sublingual, or extended-release injection), and a digital therapeutic app delivering contingency management and cognitive behavioral counseling on the primary outcome of retention in treatment. The Discontinuation phase, open to patients in stable remission from OUD and choosing to discontinue medication (including participants from the Retention phase or from the population of patients treated at the clinical site, referred by an outside prescriber or self-referred) will study different tapering strategies for buprenorphine (sublingual taper vs taper with injection buprenorphine), and a digital therapeutic app which provides resources to promote recovery, on the primary outcome of relapse-free discontinuation of medication. This paper describes how the RDD trial derives from two decades of research in the CTN. Initial trials (CTN-0001; CTN-0002; CTN-0003) focused on opioid detoxification, showing buprenorphine-naloxone was effective for detoxification, but that acute detoxification did not appear to be an effective treatment strategy. Trials on comparative effectiveness of medications for opioid use disorder (MOUD) (CTN-0027; CTN-0030; and CTN-0051) highlighted the problem of dropout from treatment and few trials defined retention on MOUD as the primary outcome. Long-term follow-up studies on those patient samples demonstrated the importance of long-term continuation of medication for many patients to sustain remission. Overall, these trials highlight the potential of a stable research infrastructure such as CTN to advance treatment effectiveness through a programmatic succession of large clinical trials.
A lack of consensus on the optimal outcome measures to assess the efficacy and effectiveness of interventions for the treatment of opioid use disorder (OUD) has hampered the pooling of research data ...for evidence synthesis and clinical guidelines. A core outcome set (COS) is a minimum set of outcome measures that are recommended for all studies of a particular condition. The National Drug Abuse Treatment Clinical Trials Network (CTN) Core Outcome Set for OUD (COS-OUD) is a development study to identify core constructs, meaningful outcomes, and their optimal measurement for all efficacy and effectiveness studies of OUD treatment and service delivery.
Overseen by an expert workgroup, a modified, stepwise, e-Delphi methodology will be used to gain consensus among a panel of clinical practitioners and researchers involved in the treatment of OUD, who are members of the CTN. Sequential rounds of anonymous, online questionnaires will be used to identify, rate the importance of, and refine a core outcome set. A consensus threshold will be achieved if at least 70% of the panel rate the measure as critical for inclusion in the COS-OUD. Where consensus is not reached or there are suggestions for new measures, these will be brought forward to a further round of review prior to a consensus meeting. Products from this study will be communicated via peer-reviewed scientific journals and conferences.
This initiative will develop a COS for OUD intervention trials, treatment studies, and service delivery and will support the pooling of research and clinical practice data and efforts to develop measurement-based care within the OUD treatment cascade.
http://www.comet-initiative.org/Studies/Details/1579.
•Counseling and 12-Step attendance were associated with later reduced opioid use.•Associations between psychosocial support and use grew over weeks of the trial.•12-Step had a larger association with ...reduced opioid use for those on naltrexone.•Group counseling had larger association with reduced use for buprenorphine-naloxone.•Relationship between psychosocial support and use are not causal; may be reciprocal.
Psychosocial support is recommended in conjunction with medication for opioid use disorder (MOUD), although optimal “dose,” modality, and timing of participation is not established. This study comprised a secondary analysis of counseling and 12-Step attendance and subsequent opioid use in a MOUD randomized clinical trial. Methods: The parent study randomly assigned 570 participants to receive buprenorphine-naloxone (BUP-NX, n=287) or extended-release injectable naltrexone (XR-NTX, n=283). Mixed-effects logistic regression models were fit with opioid use as the response variable, and a counseling/12-Step attendance predictor. Differences by treatment assignment were examined. Results: Any counseling or 12-Step attendance was associated with reduced odds of opioid use at the subsequent visit, whether considered individually or aggregated across type. A continuous relationship was observed for 12-Step attendance (F(1,5083)=5.01, p=.025); with each additional hour associated with 13% (95% CI: 0.83, 0.90) reduction in odds of opioid use. The strength of this association grew over time. In the BUP-NX arm, group counseling was associated with a greater reduction in odds of opioid use than for XR-NTX, (OR=0.32 (95% CI: .22, 0.48) vs. OR=0.69 (95% CI: 0.43, 1.08)). For XR-NTX, 12-Step was associated with a greater reduction in odds of opioid use (OR=0.35 (95% CI: 0.22, 0.54) vs. OR=0.65 (95% CI: 0.47, 0.89) for BUP-NX)). Conclusions: Psychosocial engagement has a proximal association with opioid use, the strength of that association may grow with dose and time. Alternatively, more motivated individuals may both attend more counseling/12-Step and have better treatment outcomes, or the relationship may be reciprocal.
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