Search the Library

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:

The extent to which behavioral drug abuse treatments affect sexual risk behaviors is largely unknown. This study examined the impact of behavioral drug abuse treatments on sexual risk behaviors using an integrative data analysis approach across eight trials conducted within the NIDA Clinical Trials Network (CTN-0004, 0005, 0006, 0007, 0009, 0013, 0015, and 0021). Participants (N=1305) from eight randomized controlled trials who were sexually active at baseline were included in the pooled dataset; 48.7% were female, 64.1% self-identified as a racial/ethnic minority, with M (SD) age of 34.9 (9.6). Longitudinal logistic regression estimated the probability of risky sexual behavior (i.e., inconsistent condom use and/or > 1 sexual partner in past 30 days) post-intervention with an indicator variable (1 for post-intervention), study condition (control, intervention), and their interaction as predictors; the analysis employed random effects for each trial and included relevant control variables. Time-varying differences in effects based on weeks post-intervention were incorporated using interacted linear and quadratic terms with condition status. Approximately 84.2% reported risky sexual behaviors at baseline. The control and intervention conditions were 18.5 and 17.3 percentage points less likely to report risky sexual behavior post-intervention, respectively.

Conclusions: Results suggest decreasing rates of risky sex engagement until 8 weeks (control) or 9 weeks (intervention post-intervention; risky sexual behavior subsequently increased. Behavioral CTN trial participation was associated with decreased sexual risk behaviors in both the intervention and control trial conditions. Given the heterogeneity of treatment approaches employed across the 8 CTN trials, these results point to the effectiveness of behavioral drug abuse treatment to reduce sexual risk behaviors. To bolster further reductions in sexual risk behavior engagement, there is a need to identify HIV risk reduction interventions that can best be integrated within existing resource-limited substance use disorder treatment programs.

Related protocols: CTN-0004, CTN-0005, CTN-0006, CTN-0007, CTN-0009, CTN-0013, CTN-0015, CTN-0021

Abstract:

Approximately 35% of pregnant substance users in treatment report alcohol abuse, which increases the risk of fetal alcohol spectrum disorders (FASD) in their offspring. The present study was a preliminary evaluation of the efficacy of motivational enhancement therapy (MET) in decreasing alcohol use in pregnant women attending substance use treatment, performed via a secondary analysis of a trial evaluating the efficacy of MET, relative to treatment as usual (TAU), in improving treatment outcomes in 200 pregnant substance users (CTN-0013: Motivational Enhancement Therapy to Improve Treatment Utilization and Outcome in Pregnant Substance Users). The analysis included the 41 women (n=27 MET and n=14 TAU) who reported alcohol use in the 28 days prior to randomization. Alcohol and illicit drug use days were assessed with self-report; illicit drug use was assessed with urine drug screens. All measures were obtained weekly for the 4 week active study phase and at 1 and 3 month follow-ups.

Significant treatment-by-time interaction effects were found for illicit drug use days during the active and follow-up phases and for alcohol use during the follow-up phase, all reflecting a beneficial effect for MET, relative to TAU. All other treatment effects were non-significant.

Conclusions: With FASD occurring in 2-5% of all U.S. live births, it is imperative that women who drink any amount of alcohol that could be risky to the developing fetus receive effective interventions to assist with decreased prenatal alcohol use. With approximately 35% of pregnant substance users in treatment reporting alcohol abuse, this study provides preliminary support for the use of MET to decrease prenatal alcohol use in substance using women. With a large proportion of these women abusing alcohol in combination with other substances, MET may also be useful in decreasing illicit drug use in the population, bettering outcomes for both mothers and children.

Related protocols: CTN-0013

Abstract:

Decreasing smoking during pregnancy is a priority in both research and clinical practice. In contrast, despite the high prevalence of smoking in pregnant substance users (upward of 90%), smoking-cessation treatment has received relatively little attention in substance use disorder treatment. Several barriers to integrating smoking cessation treatment interventions into SUD treatment have been delineated, including the belief that smoking is unrelated to substance use and that substance using smokers don’t want to quit smoking. Research has demonstrated these beliefs may not be accurate, but less is known about all these factors in pregnant women.

The goal of this secondary analysis was to test hypotheses that in pregnant substance users: (1) cigarette smoking would be associated with greater alcohol and drug use; (2) approximately 50% of smokers would be interested in quitting smoking; and (3) greater self-efficacy and lower perceived difficulty of smoking would be associated with interest in quitting smoking.

Data from a randomized, multisite trial (CTN-0013) with 200 pregnant substance users, 145 (72.5%) of whom smoked at baseline, was analyzed. As predicted: (1) smokers had significantly greater substance use; (2) approximately half of smokers wanted to quit; and (3) smokers with a quit goal had significantly greater self-efficacy and lower perceived difficulty of quitting.

Conclusions: Smoking may be associated with more severe substance use in pregnant substance-using patients, half of whom may be interested in smoking-cessation interventions. These findings highlight the importance of addressing smoking in pregnant substance users. While some work is being done to identify effective smoking-cessation interventions for this population, this remains a significant clinical and research need.

Related protocols: CTN-0013

Abstract:

Childhood abuse and partner violence are associated with prenatal substance abuse, but the potential impact of current family discord, which reflects broader family relationships and encompasses problems less severe than violence, has had little evaluation in pregnant substance users. Using data from 196 pregnant substance users participating in the National Drug Abuse Treatment Clinical Trials Network study CTN-0013 (Motivational Enhancement Therapy to Improve Treatment Utilization and Outcome in Pregnant Substance Users), the authors examined the relationship of baseline family discord to substance use and treatment session attendance. Family discord was assessed using items from the family composite of the Addiction Severity Index. Substance use was assessed by the Substance Use Calendar and urine drug screens (UDS). Assessments were weekly for four weeks and at two- and four-month post-randomization. Women with family discord were more likely to report living with a problematic substance user, reported a higher percentage of substance use days throughout each study phase, had a greater proportion of positive UDS over the four-month study period, and attended more weeks of treatment during the first month.

Conclusions: As hypothesized, women with family discord reported more days of substance use relative to women without family discord during each study phase. This is the first demonstration that family discord is associated with greater substance use for women who are both pregnant and have a substance use disorder. Specific treatment interventions targeting pregnant women experiencing family discord may be warranted.

Related protocols: CTN-0013

Abstract:

This ancillary investigation examined whether therapist effects may account for treatment outcomes among pregnant substance users in controlled and naturalistic treatments. Therapists participating in protocol CTN-0013 (“Motivational Enhancement Therapy to Improve Treatment Utilization and Outcome in Pregnant Substance Users”) who were randomized to Motivational Enhancement Therapy (MET) and treatment as usual (TAU) conditions and assigned at least five clients were included. Client self-reported substance use and urine toxicology at post-treatment, 1- and 3-month follow-ups were obtained. A therapist main effect was found across therapy conditions and within MET (five therapists) but not within TAU (five therapists). When substance use was treated as a dichotomous measure (abstinence/nonabstinence) corroborated with urine toxicology screening, no therapist effect was found. Clients perceived therapists to vary in their supportiveness and listening skills, for example, but these impressions were not associated with therapist effectiveness to reduce substance use.

Conclusions: The researchers found support for a limited therapist effect, but only within the MET condition and only with a continuous outcome variable. Secondary analyses identified differences in client impressions of their therapist, but those impressions did not predict therapist effectiveness in reducing substance use. Although these findings warrant replication, they suggest that client substance use outcomes among pregnant women may be rather homogeneous regardless of the type of intervention or therapist.

Related protocols: CTN-0013

Abstract:

Selection of appropriate outcome measures is important for clinical studies of drug addiction treatment. Researchers use various methods for collecting drug use outcomes and must consider substances to be included in a urine drug screen (UDS), accuracy of self-report, use of various instruments and procedures for collecting self-reported drug use, and timing of outcome assessments. This study sought to define a set of candidate measures to (1) assess their intercorrelation and (2) identify any differences in results. To that end, data were combined from seven completed protocols in the National Drug Abuse Treatment Clinical Trials Network (CTN), with a total of 1897 participants. Nine outcome measures were defined, based on UDS, self-report, or a combination, then multivariable, multilevel generalized estimating equation models were used to assess subgroup differences in intervention success, controlling for baseline differences and accounting for clustering by CTN protocols. Results found high correlations among all candidate outcomes. All outcomes showed consistent overall results with no significant intervention impact on drug use during follow-up. However, with most UDS variables, but not with self-report or “corrected self-report,” a significant gender–ethnicity interaction with benefit shown in African American women, White women, and Hispanic men was observed.

Conclusions: Despite strong associations between candidate measures, important differences in results were found. This study demonstrates the potential utility and impact of combining UDS and self-report data for drug use assessment. The results suggest possible differences in intervention efficacy by gender and ethnicity, but highlight the need to cautiously interpret observed interactions. Additional studies like this one will help guide implementation of methodological recommendations to construct combined measures.

Abstract:

HIV continues to be a significant problem among substance users and their sexual partners in the United States. The National Drug Abuse Treatment Clinical Trials Network (CTN) offers a national platform for effectiveness trials of HIV interventions in community substance abuse treatment programs. This article presents the HIV-related activities of the CTN during its first 10 years. While emphasizing CTN HIV protocols, this article reviews the (1) HIV context for this work; (2) the collaborative process among providers, researchers, and National Institute on Drug Abuse CTN staff, on which CTN HIV work was based; (3) results of CTN HIV protocols and HIV secondary analyses in CTN non-HIV protocols; and (4) implications for future HIV intervention effectiveness research in community substance abuse treatment programs.

Conclusions: While the feasibility of engaging frontline providers in this research is highlighted, the limitations of small to medium effect sizes and weak adoption and sustainability in everyday practice are also discussed.

Related protocols: CTN-0010, CTN-0013, CTN-0015, CTN-0017, CTN-0018, CTN-0019, CTN-0032

Abstract:

There is need to improve treatment effectiveness for stimulant misusers, and one means of doing so is by tailoring services to account for the common diagnostic comorbidities and psychosocial challenges this population can face. Using its publicly available datasets, this CTN-approved secondary analysis project examined prevalence of alcohol use disorders (AUDs) among primary stimulant misusing treatment-seekers as well as impact of AUD comorbidity on their pre-treatment psychosocial functioning. Upon identifying a primary stimulant misuser subsample (N = 1133) from among aggregated treatment-seekers across eight CTN trials, diagnostic data were used to document lifetime AUD rates. Paired comparisons, stratified by stimulant drug type (e.g., amphetamine, cocaine) then tested the influence of AUD comorbidity on psychosocial indices from the Addiction Severity Index–Lite. A high AUD rate (45%) was found in this client population. Among primary cocaine misusers, those with AUD were more likely to: (1) show elevated Addiction Severity Index composite scores, (2) perceive greater importance of drug treatment, and (3) endorse psychiatric symptoms and perceived need for their treatment. Among primary amphetamine misusers, those with AUD were more likely to endorse specific psychiatric symptoms.

Conclusions: Study findings document AUD comorbidity as a fairly common diagnostic feature of primary stimulant misusers, and suggest it is a pervasive influence on the pre-treatment psychosocial functioning of cocaine misusers. This study demonstrates the utility of CTN common assessment battery for secondary analysis projects, though challenges noted during its conduct highlight the value of consistent data collection and documentation within and across CTN trials.

Related protocols: CTN-0004, CTN-0006, CTN-0007, CTN-0009, CTN-0013, CTN-0017, CTN-0018, CTN-0019

Abstract:

This poster describes a study that aimed to identify for whom brief, motivation-enhancing interventions for substance use are effective, using exploratory secondary analyses of the combined datasets from four randomized National Drug Abuse Treatment Clinical Trials Network protocols (CTN-0004, -0005, -0013, and -0021) examining Motivational Interviewing / Motivational Enhancement Therapy versus Counseling as Usual (CAU). Participants were randomized to individual sessions of CAU or MET (3 sessions) / MI (1 session, CTN-0005). Other outpatient group treatment was provided as usual. All studies assessed post-intervention outcomes 4 weeks post-randomization. Participants (N=1520) were recruited from 18 outpatient treatment programs across the U.S. The majority (75%) were never married, divorced, separated, or widowed; 37% were Caucasian; and 37% were female. Almost half (40%) had a positive UDS at baseline. The MET/MI (TRT; n = 741) and CAU (n = 779) conditions were collapsed across studies and both groups were analyzed separately using direct logistic regression. There were no specific hypotheses about the order or importance of the predictors. Hispanic participants had significantly lower odds of first session completion compared to Caucasians. In both groups, positive UDS at baseline and higher Addiction Severity Index (ASI) Employment Problems scores were significantly associated with lower odds of completing three sessions. For both the TRT and CAU groups, positive UDS at baseline, higher ASI Drug Use scores, and higher ASI Medical Problems scores were significantly associated with lower odds of abstinence at end-of-treatment. Results indicate clients most in need of drug use treatment (those who have used near treatment entry and have greater drug use, medical problem, and employment problem severity), are less likely to complete or benefit from outpatient treatment as usual or outpatient treatment with motivation enhancement. These results may indicate a higher level of care is more appropriate for clients with more severe drug use problems. Additional research is needed to determine if more MET sessions earlier in treatment can positively impact treatment attendance and abstinence outcomes.

Related protocols: CTN-0004, CTN-0005, CTN-0013, CTN-0021

Abstract:

The National Drug Abuse Treatment Clinical Trials Network (CTN) has faced many challenges over its first eleven years. This review explores some of these challenges and the paths the CTN took to meet these challenges, including: designing clinical trials that reflect the CTN’s mission and changing public health needs, finding the synergies in the varied expertise of clinical treatment providers and academic researchers, promoting evidence-based practices, and expanding the Network into mainstream medical practices to reach a broader patient population. Included in this exploration are specific examples from CTN clinical trials.

CTN studies have shown that quality clinical trials can be successfully implemented into practice settings unfamiliar with research logistics by taking clinicians’ practical needs and research knowledge level into account. The challenges yet to be faced in the CTN’s efforts to expand opportunities to offer existing treatments to the segment of the drug-abusing population that utilizes mainstream health care seem large, but not as large as the potential for improvements in public health.

Related protocols: CTN-0001, CTN-0002, CTN-0003, CTN-0004, CTN-0005, CTN-0006, CTN-0007, CTN-0009, CTN-0010, CTN-0011, CTN-0013, CTN-0014, CTN-0015, CTN-0017, CTN-0018, CTN-0019, CTN-0020, CTN-0021, CTN-0027, CTN-0028, CTN-0029, CTN-0030, CTN-0031, CTN-0032, CTN-0037, CTCN-0044, CTN-0047, CTN-0048, CTN-0049

Abstract:

Evidence suggests that prenatal care, healthy behaviors such as exercise and nutrition, and general stress level are associated with fetal and maternal health but there is a relative dearth of research on interventions to improve these factors in pregnant substance users. This paper reports findings from protocol CTN-0013, in which two hundred pregnant substance users entering outpatient substance abuse treatment were randomized to receive either three individual sessions of Motivational Enhancement Therapy for pregnant substance users (MET-PS) or the first three individual sessions normally provided by the program. The study evaluated the relative efficacy of MET-PS, compared to treatment as usual, on modifiable healthy behaviors and the impact of treatment when the groups were pooled.

The results suggest that MET-PS was not more effective than treatment as usual in improving modifiable healthy behaviors. When the treatment groups were pooled, the results suggest that there were significant increases in prenatal care utilization and prenatal/multi-vitamin and water consumption, and a significant decrease in stress.

Related protocols: CTN-0013

Abstract:

Participant retention is critically important for clinical research studies in the area of addictions. This study, using data from fifteen trials in the National Drug Abuse Treatment Clinical Trials Network, sought to examine predictors of retention in a series of treatment outcome studies. Studies were combined, defining retention through the final follow-up visit, and multivariate logistic regression models were used to assess predictors of study retention, focusing on age, gender, and ethnicity (non-Hispanic White, African American, and Hispanic/Other). Results found no clear pattern, however retention seemed higher in adult pharmacologic trials and lower in sexual risk reduction trials. Younger participants were more likely to drop out and, in comparison to African American participants, non-Hispanic Whites were more likely and Hispanic/Others less likely, to drop out. In terms of gender, no significant difference was found between the sexes, though a significant interaction was discovered between ethnicity and gender in relation to study retention. This interaction was largely driven by Hispanic/Other women (not in methadone treatment), who were approximately 40% less likely to be lost to follow-up than their African American counterparts. The results suggest that strategies focused on improving study retention in younger subjects, and in non-Hispanic females, may be particularly important for increasing participant retention and improving the validity of clinical trial data.

Related protocols: CTN-0001, CTN-0002, CTN-0003, CTN-0004, CTN-0005, CTN-0006, CTN-0007, CTN-0009, CTN-0010, CTN-0011, CTN-0013, CTN-0015, CTN-0018, CTN-0019, CTN-0021

Abstract:

Multisite effectiveness trials such as those carried out in the National Drug Abuse Treatment Clinical Trials Network (CTN) are a critical step in the development and dissemination of evidence-based treatments because they address how such treatments perform in real-world clinical settings. Several possible experimental designs may be chosen for such effectiveness trials. These include (a) a new treatment intervention (Tx) is compared to an existing mode of community based treatment as usual (TAU): Tx versus TAU; (b) a new intervention is added to TAU and compared to TAU alone: Tx + TAU versus TAU; or (c) a new intervention is added to TAU and compared to a control condition added to TAU: Tx + TAU versus control + TAU. Each of these designs addresses a different question and has different potential strengths and weaknesses. As of December 2009, the primary outcome paper had been published for 16 of the multisite randomized clinical trials conducted in the CTN, testing various treatments for drug abuse, HIV risk behavior, or related problems.

This paper systematically examines, for each of the completed trials, the experimental design type chosen and its original rationale, the main findings of the trial, and the strengths and weaknesses of the design in hindsight. Based on this review, recommendations are generated to inform the design of future effectiveness trials on treatments for substance abuse, HIV risk, and other behavioral health problems. Addressing the right questions, looking closely at effect size and power, as well as internal versus external validity, and more consideration for three-arm designs and cost-effectiveness will serve well the goals of effectiveness research.

Related protocols: CTN-0001, CTN-0002, CTN-0003, CTN-0004, CTN-0005, CTN-0006, CTN-0007, CTN-0009, CTN-0010, CTN-0011, CTN-0013, CTN-0015, CTN-0017, CTN-0018, CTN-0019, CTN-0021

Abstract:

The National Drug Abuse Treatment Clinical Trials Network (CTN) began in 2000 with the goal of “improv[ing] the quality of drug abuse treatment throughout the country using science as the vehicle.” Since then, 24 discrete clinical trials were launched, 20 are completed, and 15 have published main outcome papers. Of the latter, 4 tested pharmacological treatment, 8 psychosocial/behavioral treatment, 1 a combination of medication and counseling, and 2 targeted HIV/hepatitis C virus risk behavior.

In this paper, the authors review main study findings for each of the 15 completed trials, including information about the dates of data collection, design, population, treatments, and results (primary, secondary, and treatment retention when analyzed). The purpose of this review is to identify the incremental progress toward improving drug treatment made by these trials and to propose next steps for the CTN and for the field arising from these studies. The CTN provides a unique opportunity to systematically design trials that incorporate treatment improvements from previous trials and to direct efforts toward innovations most likely to be incorporated into practice. Although the NIDA CTN has accomplished a considerable amount in its first 10 years of operation, it is clear that there is considerably more to accomplish to improve the quality of the research, as well as its dissemination, to fully realize the original goal of improving the quality of drug abuse treatment with science as the vehicle.

Related protocols: CTN-0001, CTN-0002, CTN-0003, CTN-0004, CTN-0005, CTN-0006, CTN-0007, CTN-0009, CTN-0010, CTN-0013, CTN-0015, CTN-0018, CTN-0019, CTN-0021