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Abstract: High levels of missing outcome data for biologically confirmed substance use (BCSU) threaten the validity of substance use disorder (SUD) clinical trials. Underlying attributes of clinical trials could explain BCSU missingness and identify targets for improved trial design. We reviewed 21 clinical trials funded by the NIDA National Drug Abuse Treatment Clinical Trials Network (CTN) and published from 2005 to 2018 that examined pharmacologic and psychosocial interventions for SUD. We used configurational analysis-a Boolean algebra approach that identifies an attribute or combination of attributes predictive of an outcome-to identify trial design features and participant characteristics associated with high levels of BCSU missingness. Associations were identified by configuration complexity, consistency, coverage, and robustness. We limited results using a consistency threshold of 0.75 and summarized model fit using the product of consistency and coverage. For trial design features, the final solution consisted of two pathways: psychosocial treatment as a trial intervention OR larger trial arm size (complexity=2, consistency=0.79, coverage=0.93, robustness score=0.71). For participant characteristics, the final solution consisted of two pathways: interventions targeting individuals with poly- or nonspecific substance use OR younger age (complexity=2, consistency=0.75, coverage=0.86, robustness score=1.00). Conclusions: Psychosocial treatments, larger trial arm size, interventions targeting individuals with poly- or nonspecific substance use, and younger age among trial participants were predictive of missing BCSU data in SUD clinical trials. Interventions to mitigate missing data that focus on these attributes may reduce threats to validity and improve utility of SUD clinical trials. Related protocols: CTN-0002, CTN-0003, CTN-0004, CTN-0006, CTN-0007, CTN-0009. CTN-0013, CTN-0014, CTN-0015, CTN-0017, CTN-0021, CTN-0029, CTN-0030, CTN-0031, CTN-0037, CTN-0044, CTN-0046, CTN-0048, CTN-0051, CTN-0053

Abstract:

Emerging adults (roughly 18-29 years) with substance use disorders can benefit from participation in twelve-step mutual-help organizations (TSMHO), however, their attendance and participation in such groups is relatively low. Twelve-step facilitation therapies, such as the Stimulant Abuser Groups to Engage in 12-Step (STAGE-12), may increase attendance and involvement, and lead to decreased substance use.

This study used data from the NIDA Clinical Trials Network STAGE-12 protocol (CTN-0031), a multisite randomized controlled trial, to examine whether age moderated the STAGE-12 effects on substance use and TSMHO meeting attendance and participation, The original STAGE-12 study involved assessments at baseline, mid-treatment (week 4), end-of-treatment (week 8), and 3- and 6-months post-randomization; participants were adults with DSM-IV diagnosed stimulant abuse or dependence (N=450) enrolling in 10 intensive outpatient substance use treatment programs across the U.S. A zero-inflated negative binomial random-effects regression model was utilized to examine age-by-treatment interactions on substance use and meeting attendance and involvement.

Analyses found that younger age was associated with larger treatment effects for stimulant use. Specifically, younger age was associated with greater odds of remaining abstinent from stimulants in STAGE-12 versus Treatment-as-Usual; however, among those who were not abstinent during treatment, younger age was related to greater rates of stimulant use at follow-up for those in STAGE-12 compared to TAU. There was no main effect of age on stimulant use. Younger age was also related to somewhat greater active involvement in different types of TSMHO activities among those in STAGE-12 versus TAU. There were no age-by-treatment interactions for other types of substance use or for treatment attendance, however, in contrast to stimulant use; younger age was associated with lower odds of abstinence from non-stimulant drugs at follow-up, regardless of treatment condition.

Conclusions: These results suggest that STAGE-12 can be beneficial for some emerging adults with stimulant use disorder, and ongoing assessment of continued use is of particular importance. More targeted research addressing the differences between younger and older adults and their unique responses to treatment is needed, so that developmental variations can be considered in the provision of substance abuse treatment. Age-appropriate treatment could have considerable effects on clinical outcomes and public health.

Related protocols: CTN-0031

Abstract:

This secondary data analysis explored predictors and outcomes of having a 12-step sponsor among individuals receiving treatment for stimulant use disorders, inclusive of four types of 12-step groups (Narcotics Anonymous, Alcoholics Anonymous, Cocaine Anonymous, and Crystal Meth Anonymous). For the CTN Stimulant Abuse Groups to Engage in 12-Step (STAGE-12) protocol (CTN-0031), a multisite randomized trial, participants (N=471, 59% women) were recruited among adult patients in 10 U.S. community treatment programs. Participants were randomized into treatment as usual (TAU) or a 12-step facilitation (TSF) intervention (STAGE-12). Logistic regression analyses explored the extent to which participants obtained sponsors, including the extent to which treatment condition and other predictors (12-step experiences, expectations, and beliefs) were associated with having a sponsor. The relationship between end-of-treatment sponsorship and follow-up substance use outcomes was also tested.

Results found that participants were more likely to have a sponsor at the end of treatment and 3-month follow-up, with the STAGE-12 condition having higher sponsorship rates. Twelve-step meeting attendance and literature reading during the treatment period predicted having a sponsor at the end of treatment. Sponsorship at the end of treatment predicted a higher likelihood of abstinence from stimulant user and having no drug-related problems at follow-up.

Conclusions: This study extends previous research on sponsorship, which has mostly focused on alcohol use disorders, by indicating that sponsorship is associated with positive outcomes for those seeking treatment from stimulant use disorders. It also suggests that sponsorship rates can be improved for those seeking treatment from stimulant use disorders through a short-term TSF intervention.

Related protocols: CTN-0031

Abstract:

Engagement in 12-step meetings and activities has been shown to be a powerful aid to recovery from substance use disorders. However, only limited attention has been given to ethnic and racial differences in attitudes toward 12-step and involvement. This study utilized data from CTN-0031, “Stimulant Abuser Groups to Engage in 12-Step (STAGE-12),” a large multisite trial testing the effectiveness of a 12-step facilitation therapy (Twelve-Step Facilitation (TSF)) with stimulant-dependent treatment seekers. It compared baseline differences and treatment outcomes between African American and Caucasian participants. Results of the analysis found select few baseline differences (i.e., African Americans reported higher levels of spirituality than Caucasians; African American participants indicated more perceived benefits of 12-step involvement; Caucasians were more likely to endorse future involvement in 12-step). However, there were no outcome differences (e.g., substance use outcomes, 12-step meeting attendance).

Conclusions: The tested intervention, TSF, produced similar outcomes for both groups, indicating that it may be useful across racial categories. This finding is promising, given that much of the previous research on TSF treatments has focused on alcohol, and stimulant use may present unique problem profiles for African American and Caucasian individuals. That TSF performed equally well among the two study groups is important information for clinicians deciding which evidence-based practice might be best applied to a particular client.

Related protocols: CTN-0031

Abstract:

Few studies have examined the effectiveness of 12-step peer recovery support programs with drug use disorders, especially stimulant use, and it is difficult to know how outcomes related to 12-step attendance and participation generalize to individuals with non-alcohol substance use disorders (SUDs). The NIDA Clinical Trials Network study, STAGE-12, was a clinical trial of 12-step facilitation (N=471) focusing on individuals with cocaine or methamphetamine use disorders. It allowed for examination of four questions:

1. To what extent do treatment-seeking stimulant users use 12-step programs and which ones?
2. Do factors previously found to predict 12-step participation among those with alcohol use disorders also predict participation among stimulant users?
3. What specific baseline “12-step readiness” factors predict subsequent 12-step participation and attendance?
4. Does stimulant drug of choice differentially predict 12-step participation and attendance?

The four outcome variables, attendance, speaking, duties and 12-step meetings, and other peer recovery support activities, were not related to baseline demographic or substance problem history or severity. Drug of choice was associated with differential days of Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) attendance among those who reported attending, and cocaine users reported more days of attending AA or NA at 1-, 3-, and 6-month follow-ups than did methamphetamine users. Pre-randomization measures of perceived benefit of 12-step groups predicted 12-step attendance at 3- and 6-month follow-ups. Pre-randomization 12-step attendance significantly predicted number of other self-help activities at end-of-treatment, 3- and 6-month follow-ups. Pre-randomization perceived benefit and problem severity both predicted number of self-help activities at end-of-treatment self-help activities at end-of-treatment and 3-month follow-up/ Pre-randomization perceived barriers to 12-step groups were negatively associated with self-help activities at end-of-treatment and 3-month follow-up. Whether or not one participated in any duties was predicted at all times points by pre-randomization in self-help activities.

Conclusions: The primary finding of this study is one of continuity: both readiness to engage in 12-step content and specific prior attendance and active participation (defined as speaking, having duties at, or engaging in related activities) with 12-step programs were the main signs pointing to future involvement in these same areas. Based on these findings, there may be little value in continuing to explore demographic characteristics as predictors of 12-step involvement, and instead future research should focus on measures of perceptions and behaviors that are 12-step specific.

Related protocols: CTN-0031

Abstract:

Decision-making processes have been posited to affect treatment outcome in addiction patients. This multi-site study assessed whether two measures of decision-making predicted relapse and subsequent use in stimulant-dependent patients. A total of 160 methamphetamine- or cocaine-dependent patients participating in a multi-site clinical trial evaluating a modified 12-step facilitation intervention for stimulant-dependent patients (NIDA Clinical Trials Network protocol CTN-0031, STAGE-12) were assessed. Decision-making processes of risk and delay (Iowa Gambling Task (IGT)) and response reversal (Wisconsin Card Sorting Task (WCST)) were obtained shortly after treatment admission followed by assessment of stimulant use over the next six months. The relationships of the IGT and WCST (Perseverative Errors) with relapse (yes/no) and days of stimulant use during the period following post-randomization were evaluated.

Performance on the IGT and WCST did not significantly predict relapse status or time to relapse. Unexpectedly, worse performance on the IGT was associated with fewer number of stimulant use days (p=0.001). In contrast, worse performance on the WCST (fewer perseverative errors) was associated with a greater number of stimulant use days (p=0.0003). The predictive effects of perseverative errors on subsequent use were confined to methamphetamine-dependent and minority participants.

Conclusions: Decision-making processes, as measured in the current study, do not uniformly predict relapse or subsequent use. A decrease in the salience attribution of non-drug reinforcers may explain the positive relationship between IGT performance and post-relapse use. More comprehensive and global measures of impulsiveness may better assess relapse risk and use.

Related protocols: CTN-0031

Abstract:

Oxidative stress can result in damage to the brain and other organs. To protect from oxidative damage, the human body possesses molecular defense systems, based on the activity of antioxidants, and enzymatic defense systems, including the enzymes catalase (CAT), superoxide dismutase (SOD), and thutathione peroxidase (GSH-Px). Although pre-clinical research has shown that stimulant use is associated with oxidative damage, oxidative stress and the antioxidant defense systems have not been evaluated in clinical samples of stimulant-dependent patients.

This secondary analysis of data from the National Drug Abuse Treatment Clinical Trials 12-Step Facilitation for Stimulant Abusers (STAGE-12) study aimed to investigate the link between stimulant dependence and oxidative stress. Peripheral blood samples from 174 methamphetamine (n=48) and/or cocaine-dependent (n=126) participants as well as 30 normal control participants were analyzed for the enzyme activities of CAT, SOD, and GSH-Px, in the erythrocytes and the total antioxidant capacity and malondialdehye concentration in the plasma. Results showed an association of stimulant dependence with a depletion of total antioxidant capacity to 54.6 +/- 4.7%, which correlates with a reduced activity of the SOD to 71.3+/-0.03% compared with healthy control participants (100%).

Conclusions: This is the first study to evaluate oxidative stress and antioxidant defense systems in a clinical sample of stimulant-dependent patients. Consistent with pre-clinical research findings demonstrating that stimulants decrease total antioxidant activity, the present study revealed that TAC was significantly lower in both cocaine-dependent and methamphetamine-dependent patients relative to normal controls. This could, in turn, render stimulant-dependent patients at greater risk for oxidative damage to the brain and other organs. Future research to replicate and extend these findings is warranted.

Related protocols: CTN-0031, CTN-0031-A-1

Abstract:

This study examined associations of therapeutic alliance and treatment delivery fidelity with treatment retention in Stimulant Abusers to Engage in Twelve-Step (STAGE-12), a community-based trial of 12-Step Facilitation (TSF) conducted within the National Drug Abuse Treatment Clinical Trials Network (CTN). The STAGE-12 trial randomized 234 stimulant abusers enrolled in 10 outpatient drug treatment programs to an eight-session, group and individual TSF intervention. During the study, TSF participants rated therapeutic alliance using the Helping Alliance questionnaire-II (HAq-II). After the study, independent raters evaluated treatment delivery fidelity of all TSF sessions on adherence, competence, and therapist empathy. Poisson regression modeling examined relationships of treatment delivery fidelity and therapeutic alliance with treatment retention (measured by number of sessions attended) for 174 participants with complete fidelity and alliance data. Therapeutic alliance (p=.005) and therapist competence (p=.010) were significantly associated with better treatment retention. Therapist adherence was associated with poorer retention in a nonsignificant trend (p=.061).

Conclusions: Stronger therapeutic alliance and higher therapist competence in the delivery of TSF intervention were associated with better treatment retention whereas treatment adherence was not. Training and fidelity monitoring of TSF should focus on general therapist skills and therapeutic alliance development to maximize treatment retention. This is the first study to show a relationship between therapeutic alliance and retention in TSF with substance abusers, and to identify a significant fidelity-retention relationship for manual-guided TSF treatment, a finding that has important implications for treatment delivery.

Related protocols: CTN-0031

Abstract:

This symposium presented findings from the National Drug Abuse Treatment Clinical Trials Network focused on gender differences in four different studies: Stimulant Abuser Groups to Engage in 12-Step (STAGE-12, CTN-0031); Web Delivery of Evidence-Based, Psychosocial Treatment for Substance Use Disorders (CTN-0044); Screening, Motivational Assessment, Referral and Treatment in Emergency Departments (SMART-ED, CTN-0047); and Stimulant Reduction Intervention Using Dosed Exercise (STRIDE, CTN-0037).

Presentations included:

Introduction

Elizabeth A. Wells, PhD, University of Washington
Gender Differences in Response to a 12 Step Engagement Intervention.

Aimee N.C. Campbell, PhD, MSW, Columbia University in the City of New York
Gender Differences in Acceptability and Treatment Outcomes of a Web Based Psychosocial Intervention.

Audrey Brooks, PhD, University of Arizona
Gender Differences in Treatment Access and Outcome Following an ED SBIRT Intervention.

Therese K. Killeen, PhD, Medical University of South Carolina
Stimulant Reduction Intervention Using Dosed Exercise: Gender Differences/Treatment Acceptability.

Discussant: Shelly F. Greenfield, MD, MPH, Harvard Medical School

Related protocols: CTN-0031, CTN-0037, CTN-0044, CTN-0047

Abstract:

This ancillary investigation of data from National Drug Abuse Treatment Clinical Trials Network protocol CTN-0031 (“Stimulant Abuser Groups to Engage in 12-Step (STAGE-12)”), examined whether level of exposure to the STAGE-12 intervention, a 12-step facilitative therapy, is related to treatment outcome. The original study compared STAGE-12 combined with treatment-as-usual (TAU) to TAU alone. These analyses include only those randomized to STAGE-12 (n=234). Assessments occurred at baseline and 30, 60, 90, and 180 days following randomization. High-exposure patients (n=158; attended at least 2 of 3 individual and 3 of 5 group sessions), compared to those with less exposure (n=76), demonstrated: (1) higher odds of self-reported abstinence from, and lower rates of, stimulant and non-stimulant drug use; (2) lower probabilities of stimulant-positive urines; (3) more days of attending and lower odds of not attending 12-Step meetings; (4) greater likelihood of reporting no drug problems; (5) more days of duties at meetings; and (6) more types of 12-Step activities. Many of these differences declined over time, but several were still significant by the last follow-up.

Conclusions: Although outpatient substance use disorder treatment is thought to be characterized by high drop-out rates and low rates of treatment completion, exposure to STAGE-12 treatment was relatively high for this 8-session intervention embedded within intensive outpatient treatment as usual. Over two-thirds of patients met criteria for high exposure to the intervention, and there was relatively low early attrition. Those achieving high exposure to STAGE-12 demonstrated more positive outcomes, though the design of this secondary analysis cannot demonstrate a causal relationship between STAGE-12 exposure and positive outcomes. However, the current study demonstrates that it is feasible to interest people entering intensive outpatient treatment in a 12-Step oriented intervention and that individuals who agree to participate can be retained in the intervention at relatively high rates.

Related protocols: CTN-0031

Abstract:

Given that treatment dropout among stimulant abusers has been found in prior research to be associated with relapse and continued substance use, identifying variables that best predict treatment completion for particular subgroups among stimulant abusers may aid clinicians in targeting dropout prevention strategies. The purpose of this study was to explore the selection of predictor variables in the evaluation of drug treatment completion using an ensemble approach with classification trees. The basic methodology is reviewed and the subagging procedure of random subsampling is applied. Among 234 individuals with stimulant use disorders randomized to a 12-step facilitative intervention shown to increase stimulant use abstinence (National Drug Abuse Treatment Clinical Trials Network study CTN-0031, “STAGE-12”), 67.52% were classified as treatment completers. A total of 122 baseline variables were used to identify factors associated with completion. The number of types of self-help activity involvement prior to treatment was the predominant predictor. Other effective predictors included better coping self-efficacy for substance use in high-risk situations, more days of prior meeting attendance, greater acceptance of the disease model, higher confidence for not resuming use following discharge, lower ASI Drug and Alcohol composite scores, negative urine screens for cocaine or marijuana, and fewer employment problems.

Conclusions: The application of an ensemble subsampling regressions tree method utilizes the fact that classification trees are unstable but, on average, produce an improved prediction of the completion of drug abuse treatment. The results support the notion that there are early indicators of treatment completion that may allow for modification of approaches more tailored to fitting the needs of individuals and potentially provide more successful treatment engagement and improved outcomes. Given these results, in addition to considering mostly static variables like race, gender, or marital status, researchers should attend to the selection of more dynamic variables, such as confidence and self-efficacy, that may have stronger implications in the development of treatment interventions.

Related protocols: CTN-0031

Abstract:

This ancillary investigation of data from National Drug Abuse Treatment Clinical Trials Network protocol CTN-0031 (“Stimulant Abuser Groups to Engage in 12-Step (STAGE 12)”) investigated the correspondence among four groups of raters on adherence to STAGE-12, a manualized 12-step facilitation (TSF) group and individual treatment targeting stimulant abuse. The four rater groups included the study therapists, supervisors, study-related (“TSF expert”) raters, and non-project-related (“external”) raters. Results indicated that external raters rated most critically Mean Adherence — the mean of all the adherence items — and global performance. External raters also demonstrated the highest degree of reliability with the designated expert. Therapists rated their own adherence lower, on average, than did supervisors and TSF expert raters, but therapist ratings also had the poorest reliability.

Conclusions: Findings highlight the challenges in developing practical, but effective methods of fidelity monitoring for evidence-based practice in clinical settings. While funding and licensing agencies increasingly call for use of evidence-based treatments, community-based organizations implementing them will seek the simplest, most reliable and cost-effective ways of monitoring their delivery. These results suggest that there may be a role for on-site therapists or supervisors rating adherence, and that raters unaffiliated with the treatment being tested may provide the most objective ratings. Future research should examine the impact of training therapists on self-rating to determine whether this group and achieve acceptable reliability and objectivity in ratings.

Related protocols: CTN-0031

Abstract:

This study examined the relationships between treatment fidelity and treatment outcomes in a community-based trial of 12-Step Facilitation (TSF) intervention. In a prior multi-site randomized clinical trial, National Drug Abuse Treatment Clinical Trials Network protocol CTN-0031, 234 participants in 10 outpatient drug treatment clinics were assigned to receive the Stimulant Abuser Groups to Engage in 12-Step (STAGE-12) intervention. This secondary analysis reviewed and coded all STAGE-12 sessions for fidelity to the protocol, using the Twelve Step Facilitation Adherence Competence Empathy Scale (TSF-ACES). Linear mixed-effects models tested the relationship between three fidelity measures (adherence, competence, empathy) and six treatment outcomes (number of days of drug use and five Addiction Severity Index (ASI) composite scores) measured at 3 months post-baseline. Adherence, competence, and empathy were robustly associated with improved employment status at follow up. Empathy was inversely associated with drug use, as was competence in a non-significant trend (p=.06). Testing individual ASI drug composite score items suggested that greater competence was associated with fewer days of drug use and, at the same time, with an increased sense of being trouble or bothered by drug use.

Conclusions: Greater competence and empathy in the delivery of a TSF intervention were associated with better drug use and employment outcomes, while adherence was associated with employment outcomes only. Higher therapist competence was associated with lower self-report drug use, and also associated with greater self-report concern about drug use. The nature of TSF intervention may promote high levels of concern about drug use even when actual use is low. This study is suggestive, but not conclusive, that higher fidelity intervention is associated with improved treatment outcome.

Related protocols: CTN-0031, CTN-0031-A-3

Abstract:

Therapist characteristics may be associated with variation in consistency, quality and effectiveness of treatment delivery. This ancillary investigation of National Drug Abuse Treatment Clinical Trials Network protocol CTN-0031 (Stimulant Abuser Groups to Engage in 12-Step (STAGE-12)) examined associations between treatment fidelity and therapist education, experience, treatment orientation, and perceived skills. Raters scored audio-recorded TSF sessions (n=966; 97% of TSF sessions) from 32 community-based, trained therapists for adherence, competence, empathy, and global session performance. Therapists with graduate degrees had significantly higher adherence and global performance fidelity ratings. Therapists reporting more positive attitudes toward 12-Step groups had lower adherence ratings. Being in recovery was associated with lower fidelity in univariate tests, but higher adherence in multivariate analysis. Fidelity was higher for therapists reporting self-efficacy in basic counseling skills and lower for self-efficacy in addiction-specific counseling skills. Fidelity was also superior in group relative to individual TSF sessions.

Conclusions: Results from this study have implications for therapist selection, training, and supervision in community-based, effectiveness trials and community implementation of evidence-based treatments. To obtain high fidelity and improve outcomes, it may be preferable to choose masters level therapists who are open to learning new treatments and have good, general counseling skills.

Related protocols: CTN-0031, CTN-0031-A-3

Abstract:

This is the primary outcomes paper for CTN-0031.

This study, National Drug Abuse Treatment Clinical Trials Network protocol CTN-0031, evaluated the effectiveness of an 8-week combined group plus individual 12-step facilitative intervention on stimulant drug use and 12-step meeting attendance and service. Using a multisite randomized controlled trial, with assessments at baseline, mid-treatment, end of treatment, and 3- and 6-month post-randomization follow-ups (FUs), individuals with stimulant use disorders (n=471) were randomly assigned to treatment as usual (TAU) or TAU into which the Stimulant Abuser Groups to Engage in 12-Step (STAGE-12) intervention was integrated. The STAGE-12 intervention used group sessions focused on increasing acceptance of 12-step principles, as well as individual sessions incorporating an intensive referral procedure connecting participants to 12-step volunteers. Compared with TAU, STAGE-12 participants had significantly greater odds of self-reported stimulant abstinence during the active 8-week treatment phase; however, among those who had not achieved abstinence during this period, STAGE-12 participants had more days of use. STAGE-12 participants had lower Addiction Severity Index Drug Composite scores at and a significant reduction from baseline to the 3-month FU, attended 12-step meetings on a greater number of days during the early phase of active treatment, engaged in more other types of 12-step activities throughout the active treatment phase and the entire FU period, and had more days of self-reported service at meetings from mid-treatment through the 6-month FU.

Conclusions: The present findings are mixed with respect to the impact of integrating the STAGE-12 intervention into intensive outpatient drug treatment compared with treatment as usual on stimulant drug use. However, the results more clearly indicate that individuals in STAGE-12 had higher rates of 12-step meeting attendance and were engaged in more related activities throughout both the active treatment phase and the entire 6-month follow-up period than did those in treatment as usual.

Related protocols: CTN-0031