Research Findings - CTN-Related Research
Special Issue of the Journal of Substance Abuse Treatment (JSAT)
In January 2010, JSAT released the electronic pre-publication version of a special supplement focused on the CTN and its accomplishments. Developed in honor of the CTN's 10th anniversary, this special issue -- "A Decade of Research by the National Drug Abuse Treatment Clinical Trials Network" -- features overview articles describing the completed studies and outcomes from the past decade of CTN research. It also reviews several ancillary and secondary investigations, where data from original CTN trials is analyzed to reveal new correlations, identify subpopulation variations and propose future research directions. J Subst Abuse Treat. 2010 Jun;38 Suppl 1:S1-124.
The First Decade of the National Drug Abuse Treatment Clinical Trials Network: Bridging the Gap Between Research and Practice to Improve Drug Abuse Treatment
The network brings providers from community-based drug abuse treatment programs and scientists from university-based research centers together in an alliance that fosters bidirectional communication and collaboration. Collaboration enhanced the relevance of research to practice and facilitated the development and implementation of evidence-based treatments in community practice settings. The CTN's 20 completed trials tested pharmacological, behavioral, and integrated treatment interventions for adolescents and adults; more than 11,000 individuals participated in the trials. The article reviews the rationale for the CTN, describes the translation of its guiding principles into research endeavors, and anticipates the future evolution of clinical research within the Network. Tai B, Straus MM, Liu D, Sparenborg S, Jackson R, McCarty D. J Subst Abuse Treat. 2010 Jun;38 Suppl 1:S4-13.
Study Results from the Clinical Trials Network's First 10 Years: Where Do They Lead?
Since 2000, 24 discrete clinical trials were launched, 20 are completed, and 15 have published main outcomes 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 behavior. The main study findings are reviewed 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. Wells EA, Saxon AJ, Calsyn DA, Jackson TR, Donovan DM. J Subst Abuse Treat. 2010 Jun;38 Suppl 1:S14-30.
Partnerships and Pathways of Dissemination: The National Institute on Drug Abuse-Substance Abuse and Mental Health Services Administration Blending Initiative in the Clinical Trials Network
The article describes the CTN's integral role in the Blending Initiative, key partnerships and dissemination pathways through which the results of CTN trials are developed into blending products and then transferred to community treatment programs and blending initiatives involving buprenorphine, motivational incentives, and motivational incentives, and motivational interviewing. The Blending Initiative has resulted in high utilization of its products, preparation of more than 200 regional trainers, widespread training of service providers in most U.S. States, Puerto Rico, and the U.S. Virgin Islands and movement toward the development of Web-based implementation support and technical assistance. Martino S, Brigham GS, Higgins C, Gallon S, Freese TE, Albright LM, Hulsey EG, Krom L, Storti SA, Perl H, Nugent CD, Pintello D, Condon TP. J Subst Abuse Treat. 2010 Jun;38 Suppl 1:S31-43.
A Longitudinal Study of Organizational Formation, Innovation Adoption, and Dissemination Activities within the National Drug Abuse Treatment Clinical Trials Network
First, a longitudinal dataset is used to examine CTN's formation as a network of interorganizational interaction among treatment practitioners and researchers. Data indicate strong relationships of interaction and trust, but a decline in problem-centered interorganizational interaction over time. Second, adoption of buprenorphine and motivational incentives among CTN's affiliated community treatment programs is examined over three waves of data. Although adoption is found to increase with CTPs' CTN participation, there is only modest evidence of widespread penetration and implementation. Third, CTPs' pursuit of the CTN's dissemination goals are examined, indicating that such organizational outreach activities are underway and likely to increase innovation diffusion in the future. Roman PM, Abraham AJ, Rothrauff TC, Knudsen HK. J Subst Abuse Treat. 2010 Jun;38 Suppl 1:S44-52.
From Research to the Real World: Buprenorphine in the Decade of the Clinical Trials Network
Initial CTN efforts addressed the use of buprenorphine as treatment for opioid dependence. This article reviews CTN-based buprenorphine research and related efforts to overcome challenges to the implementation of buprenorphine therapy in mainstream practice. The most notable aspect of the CTN's buprenorphine research in the community setting is its demonstration that quality data can be generated without advocating any specific treatment philosophy. CTN provided valid and reliable data and gave clinicians the opportunity to incorporate the data into their own treatment philosophy. This article explores current issues and future challenges that may require additional CTN efforts. Ling W, Jacobs P, Hillhouse M, Hasson A, Thomas C, Freese T, Sparenborg S, McCarty D, Weiss R, Saxon A, Cohen A, Straus M, Brigham G, Liu D, McLaughlin P, Tai B. J Subst Abuse Treat. 2010 Jun;38 Suppl 1:S53-60.
Motivational Incentives Research in the National Drug Abuse Treatment Clinical Trials Network
The article reviews both main findings and secondary analyses from studies of abstinence incentives conducted in CTN. Previous research has supported the efficacy of tangible incentives provided contingent on evidence of recent drug abstinence. CTN conducted the first multisite effectiveness trial of this novel intervention. Study participants were stimulant abusers (N = 803) in treatment at 14 clinical sites randomly assigned to treatment as usual with or without a prize draw incentive program. Participants could earn up to $400 over 3 months for submission of drug-free urine and breath (BAL) specimens. Three-month retention was significantly improved by incentives offered to psychosocial counseling clients (50% incentive vs. 35% control retained). Ongoing stimulant drug use was significantly reduced in methadone maintenance clients (54.4% incentive vs. 38.7% control samples testing stimulant-negative). In both settings, duration of continuous abstinence achieved was improved in the incentive condition. These studies support effectiveness of one abstinence incentive intervention and highlight the different outcomes that can be expected with application in methadone maintenance versus psychosocial counseling treatment settings. Secondary analyses have shown the importance of early treatment positive versus negative urine screens in moderating the outcome of abstinence incentives and have explored both safety and cost-effectiveness of the intervention. Stitzer ML, Petry NM, Peirce J. J Subst Abuse Treat. 2010 Jun;38 Suppl 1:S61-69.
Using a Latent Variable Approach to Inform Gender and Racial/ethnic Differences in Cocaine Dependence: A National Drug Abuse Treatment Clinical Trials Network Study
This study applies a latent variable approach to examine gender and racial/ethnic differences in cocaine dependence, to determine the presence of differential item functioning (DIF) or item-response bias to diagnostic questions of cocaine dependence, and to explore the effects of DIF on the predictor analysis of cocaine dependence. The analysis sample included 682 cocaine users enrolled in two national multisite studies of the National Drug Abuse Treatment Clinical Trials Network (CTN). There were no racial/ethnic differences in cocaine dependence; however, DIF by race/ethnicity was noted. Wu LT, Pan JJ, Blazer DG, Tai B, Stitzer ML, Woody GE. J Subst Abuse Treat. 2010 Jun;38 Suppl 1:S70-79.
Pain and Continued Opioid Use in Individuals Receiving Buprenorphine-Naloxone for Opioid Detoxification: Secondary Analyses from the Clinical Trials Network
Pain complaints are common among individuals with opioid dependence. However, few studies investigate pain during opioid detoxification or the impact this pain has on continued opioid use. This secondary analysis utilized data from two Clinical Trials Network randomized controlled trials of buprenorphine-naloxone for short-term opioid detoxification to examine the extent to which pain was associated with continued opioid use during and immediately following a 13-day detoxification protocol. At follow-up, more severe pain was associated with a greater number of self-reported days of opioid use during the prior 30 days (p < .05) but was not associated with urine toxicology results collected at follow-up. These results, although mixed, have potentially important clinical implications for assessing and addressing pain during opioid detoxification. Pain that is experienced during and immediately following medically monitored detoxification may be associated with continued opioid use. These findings lend further support for continued research on pain among patients with opioid dependence. Potter JS, Chakrabarti A, Domier CP, Hillhouse MP, Weiss RD, Ling W. J Subst Abuse Treat. 2010 Jun;38 Suppl 1:S80-86.
Predicting Outpatient Treatment Entry Following Detoxification for Injection Drug Use: The Impact of Patient and Program Factors
This article examines variables that predicted outpatient treatment entry within 6 months of residential detoxification. Patient data were collected from 632 injection drug users enrolled in a randomized trial conducted at eight detoxification programs within the National Drug Abuse Treatment Clinical Trials Network (CTN) with follow-up assessments conducted at 2, 8, 16, and 24 weeks. Detoxification program characteristics were collected during this study and from a survey of CTN treatment organizations. Survival analysis found that estimated proportions of reported outpatient treatment entry varied across sites from .06 to .72. A model-building approach determined variables significantly associated with outpatient treatment entry. The best predictive model contained five program-level variables: accreditation, fewer beds, longer stays, shorter distance between detoxification and outpatient unit, and larger city population. One patient-level variable trended toward being a significant predictor: criminal justice involvement. In this model, other patient-related variables did not significantly predict entry into post-detox outpatient treatment. These included stage of change, number of previous alcohol detoxifications, heroin use in the last 30 days, living arrangements, and reporting that detox staff had recommended further treatment. Results suggest the importance of detoxification program characteristics in facilitating further treatment and the need for systems modifications to improve continuity of care. Campbell BK, Tillotson CJ, Choi D, Bryant K, DiCenzo J, Provost SE, Zammarelli L, Booth RE, McCarty D. J Subst Abuse Treat. 2010 Jun;38 Suppl 1:S87-96.
Multisite Effectiveness Trials of Treatments for Substance Abuse and Co-occurring Problems: Have We Chosen the Best Designs?
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. Nunes EV, Ball S, Booth R, Brigham G, Calsyn DA, Carroll K, Feaster DJ, Hien D, Hubbard RL, Ling W, Petry NM, Rotrosen J, Selzer J, Stitzer M, Tross S, Wakim P, Winhusen T, Woody G. J Subst Abuse Treat. 2010 Jun;38 Suppl 1:S97-112.
Equivalence of Family Functioning and Externalizing in Adolescent Substance Users of Different Race/Ethnicity
Brief Strategic Family Therapy (BSFT) for Adolescent Drug Abuse clinical trial of 480 adolescents boys and girls age 12 to 17 and their parents was designed to maximize the chance that a sufficient number of Hispanic and Black adolescents would be included to allow valid subgroup comparisons. Examination of measurement invariance is an important step to ensure valid analysis. Two construct areas important to the analysis of trial results, adolescent problem behaviors and family functioning showed a high degree of measurement invariance, which allowed valid comparisons of mean baseline differences across groups. Results showed that Black families had significantly higher initial levels of family functioning and lower levels of adolescent externalizing than either Hispanic or White non-Hispanic families. This pattern is consistent with an increased likelihood of referral of Black adolescents with more severe problems to restricted setting rather than to outpatient drug abuse treatment. This possibility highlights the importance of considering differing baseline characteristics of subgroups prior to assessing differential treatment effectiveness to prevent confounding. Feaster DJ, Robbins MS, Henderson C, Horigian V, Puccinelli MJ, Burlew KA, Szapocznik J. J Subst Abuse Treat. 2010 Jun;38 Suppl 1:S113-S124.
The Relationship between Depression and Smoking Cessation Outcomes in Treatment-seeking Substance Abusers
The National Drug Abuse Treatment Clinical Trials Network (CTN) recently completed 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. Secondary analysis considered 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 Beck Depression Inventory II (BDI-II) scores. These data suggest that evaluation and treatment of depressive symptoms may play an important role in improving smoking cessation outcomes. Sonne SC, Nunes EV, Jiang H, Tyson C, Rotrosen J, Reid MS. Am J Addict. 2010 Mar 1;19(2):111-118.
OROS-Methylphenidate or Placebo for Adult Smokers with Attention Deficit Hyperactivity Disorder: Racial/Ethnic Differences
The purpose of this study was to explore racial/ethnic differences in OROS-methylphenidate (OMPH) efficacy when added to nicotine patch and counseling for treating nicotine dependence among adult smokers with attention deficit hyperactivity disorder (ADHD). Participants (202 whites and 51 non-whites) were randomly assigned to OMPH or placebo in a multi-site, randomized controlled trial. Study outcomes were complete, prolonged, and point-prevalence abstinence at the end of treatment, and weekly ratings of ADHD symptoms, tobacco withdrawal symptoms, and desire to smoke. The rate of four-week complete abstinence was significantly higher with OMPH than placebo among non-white (OMPH=42.9%, placebo=13.3%, chi(2)(1)=5.20, p=0.02) but not white participants (OMPH=23.1%, placebo=23.5%, chi(2)(1)=0.00, p=0.95). Patterns of prolonged and point-prevalence abstinence among non-whites were similar but fell short of statistical significance. OMPH reduced ADHD symptoms in both racial/ethnic groups, and produced greater reductions in desire to smoke and withdrawal symptoms among the non-white than white participants. Change in desire to smoke, but not in withdrawal or ADHD symptoms predicted abstinence. The ability of OMPH to reduce desire to smoke among non-whites appeared to mediate the medication's positive effect on abstinence. Differential efficacy favoring non-whites of a medication for achieving smoking cessation is a potentially important finding that warrants further investigation. Covey LS, Hu MC, Winhusen T, Weissman J, Berlin I, Nunes EV. Drug Alcohol Depend. 2010 Mar 8. [Epub ahead of print].
Substance Use and High Risk Sexual Behaviors Among Women In Psychosocial Outpatient and Methadone Maintenance Treatment Programs
This study assessed the association between substance use diagnosis and sexual risk behaviors among women enrolled in both psychosocial outpatient (PS) and methadone maintenance (MM) treatment and involved in a HIV prevention intervention study within the National Institute on Drug Abuse Clinical Trials Network. Five hundred and fifteen sexually active women reported on unprotected sexual occasions (USO), anal sex, sex trading, sex with drug occasions, and multiple male sex partners at the baseline assessment. Within the PS sample, cocaine use diagnosis was associated with more than twice the risk of having multiple partners, trading sex for drugs, having anal sex, or having sex with drugs; alcohol or opioid use diagnosis was associated with fewer risk behaviors. Within the MM sample, cocaine use, alcohol use and opiate use diagnoses were each associated with one to two risk behaviors. Associations between sexual risk and substance using days were less frequent in both samples. These findings highlight the need for integration of HIV sexual prevention interventions that address the relationship between sexual risk behavior and substance use diagnoses into substance abuse treatment programs. Tross S, Hanner J, Hu MC, Pavlicova M, Campbell A, Nunes EV. Am J Drug Alcohol Abuse. 2009; 35(5): 368-374.