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Abstract: This study aimed to estimate health state utility values (HSUVs) for the key health states found in opioid use disorder (OUD) cost-effectiveness models in the published literature. Data were obtained from six trials representing 1,777 individuals with OUD in the NIDA Clinical Trials Network (CTN-0001, -0002, -0009. -0030, -0049, and -0051). Researchers implemented mapping algorithms to harmonize data from different measures of quality of life (the SF-12 Versions 1 and 2 and the EQ-5D-3 L). They performed a regression analysis to quantify the relationship between HSUVs and the following variables: days of extra-medical opioid use in the past 30 days, injecting behaviors, treatment with medications for OUD, HIV status, and age. A secondary analysis explored the impact of opioid withdrawal symptoms. There were statistically significant reductions in HSUVs associated with extra-medical opioid use (-0.002 (95% CI [-0.003,-0.0001]) to -0.003 (95% CI [-0.005,-0.002]) per additional day of heroin or other opiate use, respectively), drug injecting compared to not injecting (-0.043 (95% CI [-0.079,-0.006])), HIV-positive diagnosis compared to no diagnosis (-0.074 (95% CI [-0.143,-0.005])), and age (-0.001 per year (95% CI [-0.003,-0.0002])). Parameters associated with medications for OUD treatment were not statistically significant after controlling for extra-medical opioid use (0.0131 (95% CI [-0.0479,0.0769])), in line with prior studies. The secondary analysis revealed that withdrawal symptoms are a fundamental driver of HSUVs, with predictions of 0.817 (95% CI [0.768, 0.858]), 0.705 (95% CI [0.607, 0.786]), and 0.367 (95% CI [0.180, 0.575]) for moderate, severe, and worst level of symptoms, respectively. Conclusions: Researchers for this study observed HSUVs for OUD that were higher than those from previous studies that had been conducted without input from people living with the condition. Related protocols: CTN-0001, CTN-0002, CTN-0009, CTN-0030, CTN-0049, CTN-0051

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:

Predictors of smoking cessation (SC) treatment outcome were explored in a multisite clinical trial of SC treatment at community-based, outpatient, substance abuse rehabilitation programs affiliated with the National Drug Abuse Treatment Clinical Trials Network (protocol CTN-0009). Cigarette smokers from five methadone maintenance programs and two drug and alcohol dependence treatment programs were randomly assigned to SC treatment as an adjunct to substance abuse treatment as usual or to substance abuse treatment as usual. SC treatment consisted of group counseling (weeks 1–8) plus transdermal nicotine patch treatment (21 mg/day, weeks 1–6; 14 mg/day, weeks 7–8). Demographic and clinical predictors of smoking abstinence were evaluated among those patients assigned to the active SC condition (N = 153) using logistic regression. Results found that abstinence during treatment was positively associated with younger age, Hispanic or Caucasian (as opposed to African American) ethnicity/race, employment or student status, fewer cigarettes per day at baseline, lower severity of the primary substance problem at baseline, and higher methadone doses (among the subsample in methadone treatment).

Conclusions: During future efforts to improve smoking cessation treatments among drug- and alcohol-dependent patients, consideration should be given to adequate treatment to reduce the severity of the primary drug or alcohol problem, tailoring treatments for patients with greater severity of smoking and of the primary substance problem, and culturally sensitive interventions. Analysis of predictors of outcome may be a useful tool for treatment development.

Related protocols: CTN-0009

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:

The focus of this presentation is on the outcomes of medication studies in the CTN and how those outcomes can be applied to treatment in community-based settings. Medication studies in the CTN have included four studies on opioid dependence (buprenorphine vs. clonidine, buprenorphine taper, buprenorphine for adolescents, and the Prescription Opioid Addiction Treatment Study) and two studies on methylphenidate (methylphenidate for smokers with ADHD and methylphenidate for adolescents with ADHD and substance use disorder). Outcomes from each trial are presented, along with implications for community-based treatment providers. Overall, these protocols have demonstrated that medication studies — both straight-forward studies and highly complex ones — can be conducted safely and effectively in community drug abuse treatment programs. Staff members in these programs can be highly enthusiastic about the new therapies, something that aids in implementation, and evidence supports the fact that successful medication trials can lead to increased use of empirically validated pharmacotherapies.

The presentation ends with a look at ongoing and future medication research in the CTN, including buprenorphine for cocaine dependence, long-acting injectable naltrexone for opioid dependence, bupropion for smokers with stimulant dependence, buspirone for cocaine dependence, and treatments for cannabis dependence.

Related protocols: CTN-0001, CTN-0002, CTN-0003, CTN-0009, CTN-0010, CTN-0028, CTN-0030

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:

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:

This presentation provides an overview of the CTN protocols that examined various pharmacotherapies for opiate dependence (buprenorphine/naloxone, e.g.), smoking cessation, and adolescents.

Each protocol is described, along with its aims and conclusions, and the presentation ends with a “to-do list” for future CTN pharmacotherapy research, in the hopes that protocols about cocaine, methamphetamine, marijuana, pharmacogenetics, combination therapies (medication plus behavioral treatments), and comorbidity will be explored down the line.

Related protocols: CTN-0001, CTN-0002, CTN-0003, CTN-0009, CTN-0010, CTN-0027, CTN-0028, CTN-0029, CTN-0030

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

Abstract:

The NIDA Clinical Trials Network’s recently completed protocol CTN-0009 was a randomized, open label trial comparing treatment as usual (TAU) combined with nicotine patches plus cognitive behavioral group counseling for smoking cessation (n=153) to TAU alone (n=72) for patients enrolled in treatment programs for drug or alcohol dependence who were interested in quitting smoking. This article reports on a secondary analysis evaluating the effect of depressive symptomatology (n=70) or history of depression (n=110) on smoking cessation outcomes. A significant association was seen between measures of depression and difficulty quitting cigarettes. Specifically, there was a greater probability for smoking abstinence for those with lower baseline BDI-ll scores (Beck Depression Inventory). These data suggest that evaluation and treatment of depressive symptoms may play an important role in improving smoking cessation outcomes.

Related protocols: CTN-0009

Abstract:

Substance abusers have a large number of medical and psychiatric problems, and 70-90% are smokers. The aim of this CTN ancillary investigation was to examine the prevalence and correlates of medical and psychiatric problems in this sample of drug dependent patients who were participants in a multi-site study of smoking cessation interventions while engaged in substance abuse treatment (protocol CTN-0009, “Smoking Cessation Treatment at Community-Based Substance Abuse Rehabilitation Programs”). Descriptive analyses showed at baseline, 72.8% of participants had at least one medical problem and 64.1% had at least one psychiatric diagnosis. Medical problems correlated strongly with age, smoking severity, and pack-years; psychiatric problems correlated with gender and ethnicity. Smoking cessation treatment was associated with a moderate reduction in the ASI Medical composite score.

Conclusions: More research is needed on the possible effects of combined treatment of substance abuse and concurrent medical and psychiatric problems. Offering smoking cessation in conjunction with primary care may be a way to address the health needs of this population. Targeting smoking cessation might be an opportunity to promote engagement with comprehensive medical care, as well as an end in itself. The addiction treatment system is unique in that it is largely separate from the medical and psychiatric care delivery systems, and nicotine dependence tends to be ignored in all three. Integration of treatment could result in significant improvement in medical, psychiatric, and addiction outcomes and save costs, thus having far reaching implications for public health.

Related protocols: CTN-0009

Abstract:

Nicotine dependence is highly prevalent among drug- and alcohol-dependent patients. A multisite clinical trial of smoking cessation (SC) treatment (CTN-0009) was performed at outpatient community-based substance abuse rehabilitation programs affiliated with the National Drug Abuse Treatment Clinical Trials Network.

Cigarette smokers (N = 225) from five methadone maintenance programs and two drug and alcohol dependence treatment programs were randomly assigned in a 2:1 ratio to receive either (1) SC treatment as an adjunct to substance abuse treatment-as-usual (TAU) or (2) substance abuse TAU. Smoking cessation treatment consisted of 1 week of group counseling before the target quit date and 8 weeks of group counseling plus transdermal nicotine patch treatment (21 mg/day for Weeks 1-6 and 14 mg/day for Weeks 7 and 8) after the target quit date. Smoking abstinence rates in SC, 10%-11% during treatment and 5%-6% at the 13- and 26-week follow-up visits, were significantly better than those in TAU during treatment (p < .01). In addition, SC was associated with significantly greater reductions as compared with TAU in cigarettes smoked per day (75% reduction, p < .001), exhaled carbon monoxide levels (p < .001), cigarette craving (p < .05), and nicotine withdrawal (p < .05). Smoking cessation did not differ from TAU on rates of retention in substance abuse treatment, abstinence from primary substance of abuse, and craving for primary substance of abuse. Compliance with SC treatment, moderate at best, was positively associated with smoking abstinence rates.

Smoking cessation treatment resulted in significant reductions in daily smoking and modest smoking abstinence rates without having an adverse impact on substance abuse rehabilitation when given concurrently with outpatient substance abuse treatment. Substance abuse treatment programs should not hesitate to implement SC for established patients.

Related protocols: CTN-0009

Abstract:

Cigarette smoking is widely prevalent among individuals in treatment for drug or alcohol dependence; however, the treatment of nicotine addiction in this population has numerous obstacles at both programmatic and patient levels. Despite these difficulties, recent studies have demonstrated moderate success in implementing smoking cessation treatment in drug rehabilitation programs. The National Drug Abuse Treatment Clinical Trials Network sponsored a smoking cessation study (CTN-0009, “Smoking Cessation Treatment with Transdermal Nicotine Replacement Therapy in Substance Abuse Rehabilitation Programs”) in 13 community-based outpatient substance abuse rehabilitation programs across the country. The study evaluated the effectiveness of smoking cessation treatment provided as an adjunct to substance abuse treatment-as-usual. This report summarizes the practical and clinical experiences encountered at each of the study sites with regard to implementing the smoking cessation treatment intervention. Smoking behavior of the treatment clientele was assessed by anonymous survey at each site. In addition, sites were systematically characterized by using program review and assessment tools completed by the respective staff and program directors at the site. Survey and recruitment data indicated that cigarette smoking is more prevalent and that smoking cessation treatment is more feasible, in methadone maintenance treatment programs. Other factors associated with smoking behavior and with the recruitment of drug- and alcohol-dependent individuals into the smoking cessation treatment study are described.

Related protocols: CTN-0009