Substance use will be the common outcomes in models including participants of both HIV statuses.For example, calculating the CER for adding contingency management to Matrix for non-responders would yield a CER equation. In calculating the CER of high vs. low intensity contingency management at the first randomization stage, the entire range of subsequent costs will be included. Costs of delivering the interventions will be derived from clinic records of time and other inputs, as well as incentive payments, thus providing an estimate of CER from the medical system perspective. We will also evaluate CERs from a societal perspective, using a broad definition of costs, including the social costs of incarceration. We will conduct sensitivity analyses to estimate the extent to which the CER calculation is affected by differences in assumptions about the size of the differences in intervention effect. In particular, we will determine how sensitive the CER is to assumptions that the difference in treatment effect is one standard deviation below or above the mean estimated effect size. Similarly, we will estimate the sensitivity of conclusions to costs that are one standard deviation below or above the estimated mean.We will first describe the extent and patterns of missingness within each variable and check for associations between missing and observed data to determine the mechanism of missingness, which could be missing completely at random, missing at random,vertical farming or missing not at random. Missing data will then be handled using multiple imputation. Appropriate imputation techniques will be chosen for the type of missing data and the statistical tools employed. For sensitivity analysis, we will conduct analyses with and without multiple imputations.
All participants will be analyzed on an intent-to-treat basis where the study outcomes are examined based on the random intervention assignment and not on the actual intervention received or adherence to the intervention.There is no planned interim analysis as the behavioral therapies used in this trial have no known serious adverse events and are consistently more efficacious than control conditions in treatment-seeking participants. The effect sizes of the behavioral therapies in this trial are in the moderate range. Furthermore, any interim analysis and decision to stop the trial would likely be based on under powered data and susceptible to error.Our data monitoring committee is composed of members of the Data and Safety Monitoring Board for Addiction Medicine of the University of California – Los Angeles. These members are not connected to the study in any way. The DSMBAM is independent from the National Institute on Drug Abuse —the sponsor of this study. The DSMBAM meets quarterly to monitor subjects’ progress in the trial and considers whether adverse social harms differentially accrue by condition. Although there are no prospective stopping rules for this trial, the DSMBAM is within its charge to review aggregate data, request statistical tests of differences in social or other harms, and then advise changes in intervention type or intensity if statistically significant differences emerge in adverse events by condition. Prior to each meeting, the study team will submit a performance report including all reports of SAEs for DSMBAM’s consideration. After each meeting, recommendations will be made in writing to the principal investigators.Hanoi Medical University and the staff in the STAR-OM study provide oversight of financial management. The Vietnam teams and US teams maintain frequent communication via emails and bi-weekly online meetings to report updates on the study progress, discuss scientific aspects of the study, and troubleshoot issues when they arise.
The teams in Hanoi and HCMC meet online once weekly and in-person quarterly during monitoring visits to discuss the study conduct. We submit annual research progress reports to the Ethics Committee of Hanoi Medical University. Any protocol amendments need to get ethical approval before implementation. The UCLA Addiction Medicine Data Safety Monitoring Board independently review our data and data management twice a year.Adverse events in this trial are defined as medical issues that do not require hospitalization. Serious adverse events are defined as life-threatening events such or other events that have a negative impact on participants’ life such as incarceration or compulsory drug rehabilitation. The clinic staff will communicate information about adverse events and serious adverse events to the study team right after they are informed by participants or participant families. The study coordinators in Hanoi and HCMC are responsible to report adverse events within 7 days and serious adverse events within 24 h on REDCap with the time of onset, seriousness, duration, and outcomes. The principal investigator will decide what serious adverse events need to be reported to the Ethics Committee.Prior to participation in the trial, the participant will be informed about the research. Participants will complete a short questionnaire about the study objectives and main activities to show how they understand the study. Research assistants will provide more explanation based on the results of the questionnaire. If participants agree to join the study, they will sign a consent form. Each participant will be assigned a unique identifier at the time of screening. Participant data will be linked to this identifier only. Participant personal identifiable information is stored in a separate locked cabinet to which only responsible study staff have access. All study staff sign a confidentiality agreement to non-disclosure of participant information. We make extra efforts to ensure nodisclosure of drug use information to anyone other than participants and the study staff.Between July and October 2020, we conducted 4 focus group discussions of a convenience sample of participants from four methadone clinics in the downtown and suburbs of Hanoi and HCMC to inform intervention content and refinement. Respondents reported information on local taxonomy and patterns of methamphetamine use, triggering situations, methamphetamine related sexual risks, motivations for seeking treatment, and perceived acceptability of the adaptive interventions.
The pilot implementation lasted 12 weeks from November 2020 through February 2021. It identified issues to be addressed before the full implementation. At the conclusion of the pilot, we conducted 2 FGD with patients and 1 FGD with providers participating in the pilot to gauge their feedback about the interventions.With the cut-off point of ASSIST ≥ 4 and methamphetamine-positive UDS as originally proposed, there were 26 and 52 eligible participants in two pilot clinics in Hanoi and HCMC, respectively . For the pilot implementation, we randomly recruited 42 participants with ASSIST score ≥ 4 or methamphetamine-positive UDS. After the front line intervention, 16 participants were non-responders and randomized into adaptive interventions. At least 50% of the original sample must transition to the adaptive phase for sufficient statistical power. Thus, we decided to recruit more participants with severe use of methamphetamine, as evidenced in both ASSIST score ≥ 10 and methamphetamine-positive UDS. Furthermore, to recruit enough participants for the front line intervention phase, given most other clinics are smaller than the two pilot ones,indoor cultivation we decided to use ASSIST score “OR” UDS instead of “AND” to increase the pool of potential participants. We kept the criterion of methamphetamine-positive UDS to compensate for participants with lower ASSIST scores due to desirability bias.The STAR-OM study is among the first studies to evaluate different combinations of EBIs for methamphetamine use among methadone patients in low-and-middle-income countries. The study will provide effectiveness and cost-effectiveness evidence for scaling up these interventions. The SMART design assesses different treatment strategies for participants who respond differently to front line interventions. The combination of trial and ethnographical study will provide insights on factors at multiple levels that need to be considered in decision making. The adaptation and pilot implementation of EBIs will make them culturally sound to local participants. As the interventions will be delivered by methadone providers at methadone clinics, they can be readily implemented if the trial demonstrates they help. The participation of some participants can be interrupted due to drug-related police arrest or methadone treatment fatigue. This limitation can be minimized as we will select clinics with low drop-out rates. We have officially informed the local police on the study implementation and received approval from both national and local authorities. While this measure does not prevent participants from being arrested, especially when they are involved in illegal activities, it could reduce attrition. Furthermore, the COVID-19 pandemic and containment measures could pose challenges for the study implementation. With the response plan developed for potential interruption scenarios, we believe the study will be implemented safely and will maintain a high-level of data quality and intervention fidelity.Marijuana is one of the most widely used illicit substances world-wide. Although it has been reported that marijuana use rate has stabilized or even decreased in recent years in most high-income countries, the continuing high prevalence of use among adolescents and young adults is a cause for concern. Such emerging trends have heightened interest in the link between mental health problems and adolescent marijuana use to inform policy and prevention efforts.Marijuana use is associated with numerous different psychiatric disorders, each of which tend to co-occur with one another.
Additionally complicating matters is the potential bidirectional nature of this association, with evidence that marijuana use may both predict and result from poor zmental health. A parsimonious explanation of this comorbidity may be that a small set of transdiagnostic psychopathological vulnerabilities that give rise to numerous mental health conditions may also contribute to and result from marijuana use. Such transdiagnostic vulnerabilities may account for the pervasive patterns of psychiatric comorbidity with use of marijuana and other substances. One such transdiagnostic vulnerability is anhedonia— diminished capacity to experience pleasure in response to rewards. As a subjective manifestation of deficient reward processing capabilities, anhedonia is believed to result from hypoactive brain reward circuitry. While anhedonia is a core feature in a DSM-defined major depressive episode, it has also been linked to other psychopathologies comorbid with drug use, including psychosis, borderline personality disorder, social anxiety, attention deficit hyperactivity disorder and post-traumatic stress disorder and has therefore been proposed to be a transdiagnostic process. Departing from its consideration as a ‘symptom’ of a disease state as in DSM-defined major depression, anhedonia has also been conceptualized as a continuous dimension, upon which there are substantial inter individual differences. Individuals at the lower end of the anhedonic spectrum experience high levels of pleasure and experience robust affective responses to pleasurable events, whereas those at the upper end of this spectrum exhibit more prominent deficits in their pleasure experience. Anhedonia operates as a ‘traitlike’ dimension that is stable yet malleable, which is empirically and conceptually distinct from other emotional constructs, such as reward sensitivity , alexithymia and emotional numbing , sadness and negative affect. Recent literature documents a consistent association between anhedonia and substance use in adults. To the best of our knowledge, there has been only prior study of the association between anhedonia and marijuana use in youth, which found higher anhedonia levels among treatment-seeking marijuana users than healthy controls in a cross-sectional analysis of 62 French adolescents and young adults. Given the absence of longitudinal data, it is unclear whether anhedonia is a risk factor for or consequence of adolescent marijuana use. Because youth with higher anhedonia levels experience little pleasure from routine rewards they may seek out drugs of abuse, such as marijuana, which stimulate neural circuitry that underlie pleasure pharmacologically. Alternatively, repeated tetrahydrocannabinol exposure during adolescence produces enduring deficits in brain reward system function and anhedonia-like behavior in rodent models. In observational studies of adults, heavy or problematic marijuana use is associated with subsequent anhedonia and diminished brain reward region activity during reward anticipation. Consequently, it is plausible that anhedonia may both increase risk of marijuana use and result from marijuana use. Because early adolescence is a period in which risk of marijuana use uptake is high and the developing brain may be vulnerable to cannabinoid-induced neuroadaptations, this study estimated the strength of bidirectional longitudinal associations between anhedonia and marijuana use among adolescents during the first 2 years of high school. The primary aim was to test the following hypotheses: greater baseline anhedonia would be associated with a faster rate of escalation in marijuana use across follow-up periods; and more frequent use of marijuana at baseline would be associated with increases in anhedonia across follow-ups.