The COMBINE Study sought to answer questions about the benefits of combining behavioral and pharmacological interventions (naltrexone and acamprosate) in alcohol-dependent patients. Our goals were to identify trajectories of heavy drinking prior to randomization in COMBINE, to characterize subjects in these trajectories, and to assess whether pre-randomization trajectories predict drinking outcomes. We analyzed daily indicators of heavy drinking in 90 days prior to randomization using a trajectory-based approach. Each subject was assigned to the most-likely pre-randomization heavy drinking trajectory, and the baseline characteristics of participants in the baseline trajectories were compared. Main and interactive effects of these trajectories and treatment factors (acamprosate, naltrexone or CBI) on summary drinking measures during active treatment (16 weeks) were assessed. We identified five trajectories of heavy drinking pre-randomization: “T1: frequent heavy drinkers”, “T2: very frequent heavy drinkers”, “T3: nearly daily heavy drinkers”, “T4: daily heavy drinkers” and “T5: daily heavy drinkers stopping early” prior to randomization. Trajectory membership was significantly associated with all drinking outcomes. Subjects in “T5: daily heavy drinkers stopping early” had comparable drinking outcomes to the subjects in “T1: frequent heavy drinkers” while the remaining trajectories were associated with significantly worse outcomes. Baseline trajectory did not interact significantly with treatment condition. These exploratory analyses confirmed the hypothesis that baseline trajectories predict post-randomization drinking outcomes. Interestingly, “T5: daily heavy drinkers stopping early” had outcomes that were comparable to the least severe baseline trajectory “T1: frequent heavy drinkers” and baseline trajectories of heavy drinking did not moderate treatment effects.
trajectory-based analysis; clinical trial; baseline predictors; naltrexone; acamprosate; combined behavioral intervention
Adoption of contingency management (CM) by the addiction treatment community is limited to date despite much evidence for its efficacy. This study examined systemic and idiographic staff predictors of CM adoption attitudes via archival data collected from treatment organizations affiliated with the National Drug Abuse Treatment Clinical Trials Network. Multilevel modeling analyses evaluated potential predictors from organizational, treatment unit, and workforce surveys. Among these were individual and shared perceptions of staff concerning aspects of their clinic culture and climate. Modeling analyses identified three systemic predictors (clinic provision of opiate agonist services, national accreditation, lesser shared perception of workplace stress) and five idiographic predictors (staff with a graduate degree, longer service tenure, managerial position, e-communication facility, and openness to change in clinical procedures). Findings are discussed as they relate to extant literature on CM attitudes and established implementation science constructs, and their practical implications are discussed.
Clinical trials test the safety and efficacy of behavioral and pharmacological interventions in drug-dependent individuals. However, there is no consensus about the most appropriate outcome(s) to consider in determining treatment efficacy or on the most appropriate methods for assessing selected outcome(s). We summarize the discussion and recommendations of treatment and research experts, convened by the US National Institute on Drug Abuse, to select appropriate primary outcomes for drug dependence treatment clinical trials, and in particular the feasibility of selecting a common outcome to be included in all or most trials.
A brief history of outcomes employed in prior drug dependence treatment research, incorporating perspectives from tobacco and alcohol research, is included. The relative merits and limitations of focusing on drug-taking behavior, as measured by self-report and qualitative or quantitative biological markers, are evaluated.
Drug-taking behavior, measured ideally by a combination of self-report and biological indicators, is seen as the most appropriate proximal primary outcome in drug dependence treatment clinical trials.
We conclude that the most appropriate outcome will vary as a function of salient variables inherent in the clinical trial, such as the type of intervention, its target, treatment goals (e.g. abstinence or reduction of use) and the perspective being taken (e.g. researcher, clinical program, patient, society). It is recommended that a decision process, based on such trial variables, be developed to guide the selection of primary and secondary outcomes as well as the methods to assess them.
Clinical trials; drug dependence; end-points; primary outcome; self-report; toxicology; treatment research
Indigenous communities have engaged in needs and resources assessments for thousands of years. By blending CBPR/TPR approaches with community-driven assets and needs assessments, academic and community based researchers can work together to better understand and identify community strengths as well as issues of concern in Native communities. This best practice approach can set research agendas that are relevant to Native communities and result in interventions and health promotion programs that are respectful of Tribal sovereignty and that incorporate unique traditions and strengths of Native communities. A successful research partnership to develop and implement a needs and resources assessment using CBPR/TPR approaches is presented using a case study that can be used as a model for other research partnerships.
American Indian and Alaska Native; CBPR; TPR; Needs and resources assessment; Substance abuse; Cultural identity
The Desired Effects of Drinking (DEOD) is a 36-item, 9-subscale, self-report measure assessing reasons for drinking, concerning three general motives for alcohol use: Coping, Social, and Enhancement. These subscales include Negative Feelings, Self-esteem, Relief, Positive Feelings, Social Facilitation, Assertion, Drug Effects, Sexual Enhancement, and Mental effects. As part of the COMBINE study, scores from the nine DEOD subscales, along with additional information about alcohol consumption and consequences, were incorporated into personalized client feedback as part of a motivational enhancement intervention and as a guide for the development of a plan for treatment and change. With responses from a clinical sample of 572 individuals seeking alcohol treatment, the 9-subscale structure of the instrument was substantiated through a second-order confirmatory factor analysis, revealing moderately large to large factor loadings and good indices of model fit. A third-order factor analysis indicated these nine subscales adequately represented the three drinking motives. It is suggested these three general motives for alcohol use, which may be more distinctly delineated into the nine dimensions reflected in the DEOD structure, can be used clinically to help plan appropriate interventions and facilitate behavior change.
drinking motives; confirmatory factor analysis; concurrent validity; predictive validity
Community Based and Tribally Based Participatory Research (CBPR/TPR) are approaches that can be successful for developing ethical and effective research partnerships between academic institutions and Tribes and Native organizations. The NIDA Clinical Trials Network funded a multi-site, exploratory study using CBPR/TPR to begin to better understand substance abuse issues of concern to some Tribes and Native organizations as well as strengths and resources that exist in these communities to address these concerns. Each of the five sites is briefly described and a summary of the common themes for developing these collaborative research efforts is provided.
American Indian and Alaska Native; CBPR/TPR; substance abuse; strengths based research
The importance of conducting substance use disorder treatment research in real-world settings is now well recognized. While this approach to clinical trials research offers a variety of benefits, challenges also arise. Selecting high quality sites to participate is critical to recruitment, retention, and overall trial performance when conducting multi-site, community-based clinical trials of treatments for substance use disorders.
Over the past 10 years, the NIDA-sponsored National Drug Abuse Treatment Clinical Trials Network (CTN) has strived to conduct high-quality, well-managed clinical trials. This includes developing methods for site selection to be used by investigators conducting CTN trials.
Issues relevant to site selection include the clinical trial design, availability of appropriate clinical population, and organizational attributes of potential clinical research sites. Site selection strategies include reviewing regional epidemiologic data, collecting standard site selection surveys, evaluating clinic data on existing patient populations, and site selection interviews and visits.
This paper describes considerations for selecting research sites and identifies specific strategies to employ when selecting community-based sites for participation in clinical trials.
Medical settings such as emergency departments (EDs) present an opportunity to identify and provide services for individuals with substance use problems who might otherwise never receive any form of assessment, referral, or intervention. Although Screening, Brief Intervention, and Referral to Treatment (SBIRT) models have been extensively studied and are considered effective for individuals with alcohol problems presenting in emergency departments and other medical settings, the efficacy of such interventions has not been established for drug users presenting in EDs.
This paper describes the design of a NIDA Clinical Trials Network protocol testing the efficacy of an SBIRT model in medical EDs, highlighting considerations that that are pertinent to the design of other studies targeting substance use behaviors in medical treatment settings.
The protocol is described, and critical design decisions are discussed.
Design challenges included defining treatment conditions, study population, and site characteristics; developing the screening process; choosing the primary outcome; balancing brevity and comprehensiveness of assessment; and selecting the strategy for statistical analysis.
Many of the issues arising in the design of this study will be relevant to future studies of interventions for addictions in medical settings.
Optimal trial design is critical to determining how best to integrate substance abuse interventions into medical care.
Bidirectional, collaborative partnerships between academic researchers and practitioners have been a fundamental vehicle to achieve the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) goal of improving outcomes of community-based drug treatment. These partnerships blend clinical perspectives of practitioners and methodological expertise of researchers working together to address clinically meaningful issues through randomized clinical trials conducted in community treatment settings.
Bidirectionality is a guiding principle of the CTN, but its operationlization at the practical level in protocol development and implementation has not been articulated. This descriptive article presents the development of one protocol as an example and model of this bidirectional, collaborative, iterative partnership between researchers and practitioners.
This article illuminates several specific issues encountered while developing STAGE-12, a behavioral intervention to facilitate 12-step mutual support group involvement, as well as the rationale for decisions taken to resolve each.
The STAGE-12 protocol was successfully developed through a series of decisions taking into account both design factors and clinical practice needs and realities, thus maintaining a balance between methodological rigor and generalizability.
The review demonstrates the process by which research and practice have been blended in protocol development, exemplifying the underlying principle of bidirectionality, a key element in the success of the NIDA CTN.
Bidirectional partnerships as derived in the CTN, employing a hybrid model of efficacy-effectiveness research, are capable of designing and implementing protocols that are both methodologically rigorous and clinically meaningful, thus increasing likelihood of adoption and eventual improvement in public health.
bidirectionality; research; clinical practice; internal validity; external validity; clinical trials network; protocol development
Empirically-supported treatments for alcohol dependence exist, yet understanding of influences contributing to the intended behavior change is limited. The current study, a secondary analysis of the recent multi-site COMBINE trial (The COMBINE Study Research Group, 2003), tested a mediational model wherein change in client self-efficacy for abstinence was examined as a potential mediator of associations between client-report of the therapeutic bond and one-year outcomes of drinking frequency, drinking consequences, and psychiatric functioning. For analyses, the 1383 COMBINE trial participants were grouped as follows: 1) those receiving study medications (Naltrexone, Acamprosate, Naltrexone + Acamprosate, Placebo) and enrolled in medication management (MM) only (n=607), 2) those receiving study medications/MM and also enrolled in a combination behavioral intervention (CBI) as well (n=619), and 3) those enrolled in CBI only (n=157). Mediation analyses using the product-of-coefficients approach indicated self-efficacy change during treatment significantly mediated associations between the therapeutic bond with the CBI therapist and each of the three one-year outcomes among those exclusively receiving CBI, but failed to do so among those receiving pills/MM (with or without CBI). Effect sizes were small, but indicated that variance in bond-outcome associations was partially mediated by self-efficacy change for trial participants. Findings advance understanding of proximal client change processes during delivery of treatments for alcohol dependence.
alcohol treatment; therapeutic bond; self-efficacy
The COMBINE Study evaluated the effects of acamprosate, naltrexone and the Combined Behavioral Intervention (CBI). In secondary analyses, our goals were to identify trajectories of any drinking prior to randomization, to characterize subjects in these trajectories, and to assess whether pre-randomization trajectories predict drinking outcomes and moderate treatment response.
We analyzed daily indicators of any drinking in 90 days prior to randomization using a trajectory-based approach. General linear models and generalized logistic regression assessed main and interactive effects of pre-randomization drinking trajectories and treatment on summary drinking measures during active treatment.
We identified five trajectories of any drinking prior to randomization: “T1: frequent drinkers”, “T2: very frequent drinkers”, “T3: nearly daily drinkers”, “T4: consistent daily drinkers” and “T5: daily drinkers stopping early”. During treatment, “T3: nearly daily drinkers” and “T4: consistent daily drinkers” had significantly worse drinking outcomes than “T1: frequent drinkers” while “T5: daily drinkers stopping early” had comparable drinking outcomes to “T1: frequent drinkers”. Acamprosate significantly increased the chance of abstinence from heavy drinking for the “T2: very frequent drinking” trajectory but decreased the chance of abstinence from heavy drinking for “T5: daily drinkers stopping early”. Naltrexone differentially improved rates of continuous abstinence for very frequent drinkers.
Acamprosate benefited very frequent drinkers and contrary to expectations was associated with poorer response compared to placebo for consistent daily drinkers who had longer durations of pretreatment abstinence (e.g., ≥ 14 days). Baseline drinking trajectories also moderated naltrexone effects. These findings may help clinicians identify patients for whom acamprosate and naltrexone may be most beneficial.
naltrexone; acamprosate; clinical trial; latent class; trajectory-based analysis
Negative affect is a significant predictor of alcohol relapse, and the relation between negative affect and drinking has been shown to be strongly mediated by alcohol craving. Thus, targeting craving during treatment could potentially attenuate the relation between negative affect and drinking.
The current study is a secondary analysis of data from the COMBINE study, a randomized clinical trial that combined pharmacotherapy with behavioral intervention in the treatment of alcohol dependence. The goal of the current study was to examine whether a treatment module that targeted craving would predict changes in negative mood during the 16-week Combined Behavioral Intervention (CBI; n=776) and the relation between changes in mood, craving, and changes in heavy drinking during treatment and one year posttreatment.
Changes in negative mood were significantly associated with changes in heavy drinking during treatment (f2=0.78). Participants (n=432) who received the craving module had significantly fewer heavy drinking days during treatment (d = 0.31) and receiving the module moderated the relation between negative mood and heavy drinking during treatment (f2=0.92) and one year posttreatment (f2=0.03). Moderating effects of the craving module were mediated by changes in craving during treatment. Within subject analyses indicated significant pre- to post-module reductions in negative mood. Additionally, post-module craving significantly mediated the association between negative mood and heavy drinking during treatment and posttreatment.
The craving module of CBI may weaken the relation between negative affect and heavy drinking by fostering greater decreases in craving during treatment.
craving; negative mood; heavy drinking; urge surfing; behavioral intervention
A substantial body of research has established the effectiveness of brief interventions for problem alcohol use. Following these studies, national dissemination projects of screening, brief intervention (BI), and referral to treatment (SBIRT) for alcohol and drugs have been implemented on a widespread scale in multiple states despite little existing evidence for the impact of BI on drug use for non-treatment seekers. This article describes the design of a study testing the impact of SBIRT on individuals with drug problems, its contributions to the existing literature, and its potential to inform drug policy.
The study is a randomized controlled trial of an SBIRT intervention carried out in a primary care setting within a safety net system of care. Approximately 1,000 individuals presenting for scheduled medical care at one of seven designated primary care clinics who endorse problematic drug use when screened are randomized in a 1:1 ratio to BI versus enhanced care as usual (ECAU). Individuals in both groups are reassessed at 3, 6, 9, and 12 months after baseline. Self-reported drug use and other psychosocial measures collected at each data point are supplemented by urine analysis and public health-related data from administrative databases.
This study will contribute to the existing literature by providing evidence for the impact of BI on problem drug use based on a broad range of measures including self-reported drug use, urine analysis, admission to drug abuse treatment, and changes in utilization and costs of health care services, arrests, and death with the intent of informing policy and program planning for problem drug use at the local, state, and national levels.
Problem drug use; Screening; Brief Intervention and Referral to Treatment (SBIRT); Motivational Interviewing (MI); Addiction Severity Index (ASI); Safety net; Public health benefit; Cost effectiveness
Screening, brief intervention, and referral to treatment (SBIRT) approaches to reducing hazardous alcohol and illicit drug use have been assessed in a variety of health care settings, including primary care, trauma centers, and emergency departments. A major methodological concern in these trials, however, is “assessment reactivity,” the hypothesized impact of intensive research assessments to reduce alcohol and drug use and thus mask the purported efficacy of the interventions under scrutiny. Thus, it has been recommended that prospective research designs take assessment reactivity into account. The present article describes the design of the National Institute on Drug Abuse Clinical Trials Network protocol, Screening, Motivational Assessment, Referral, and Treatment in Emergency Departments (SMART-ED), which addresses the potential bias of assessment reactivity.
The protocol employs a 3-arm design. Following an initial brief screening, individuals identified as positive cases are consented, asked to provide demographic and locator information, and randomly assigned to one of the three conditions: minimal screening only, screening + assessment, or screening + assessment + brief intervention. In a two-stage process, the randomization procedure first reveals whether or not the participant will be in the minimal-screening-only condition. Participants in the other two groups receive a more extensive baseline assessment before it is revealed whether they have been randomized to also receive a brief intervention. Comparing the screening only and screening + assessment conditions will allow determination of the incremental effect of assessment reactivity.
Assessment reactivity is a potential source of bias that may reduce and/or lead to an underestimation of the purported effectiveness of brief interventions. From a methodological perspective, it needs to be accounted for in research designs. The SMART-ED design offers an approach to minimize assessment reactivity as a potential source of bias. Elucidating the role of assessment reactivity may offer insights into the mechanisms underlying SBIRT as well as suggest clinical options incorporating assessment reactivity as a treatment adjunct.
Assessment reactivity; Brief intervention; SBIRT; Clinical trials; Research design
The ultimate goal of alcohol treatment research is to develop interventions that help individuals reduce their alcohol use. To determine whether a treatment is effective researchers must then evaluate whether a particular treatment affects changes in drinking behavior after treatment. Importantly, drinking following treatment tends to be highly variable between individuals and within individuals across time.
Using data from the COMBINE study (COMBINE Study Research Group, 2003) the current study compared three commonly used and novel methods for analyzing changes in drinking over time: latent growth curve analysis, growth mixture models, and latent Markov models. Specifically, using self-reported drinking data from all participants (n = 1,383, 69% male) we were interested in examining how well the three estimated models were able to explain observed changes in percent heavy drinking days during the 52 weeks following treatment.
The results from all three models indicated that the majority of individuals were either abstinent or reported few heavy drinking days during the 52 week follow-up and only a minority of individuals (10% or fewer) reported consistently frequent heavy drinking following treatment. All three models provided a reasonably good fit to the observed data with the latent Markov models providing the closest fit. The observed drinking trajectories evinced discontinuity, whereby individuals seem to transition between drinking and non-drinking across adjacent follow-up assessment points. The latent growth curve and growth mixture models both assumed continuous change and could not explain this discontinuity in the observed drinking trajectories, whereas the latent Markov approach explicitly modeled transitions between drinking states.
The three models tested in the current study provided a unique look at the observed drinking among individuals who received treatment for alcohol dependence. Latent Markov modeling may be a highly desirable methodology for gaining a better sense of transitions between positive and negative drinking outcomes.
alcohol treatment; relapse; growth models; mixture models; heterogeneity
Many persons seeking opiate treatment present with complex clinical challenges, which may be exacerbated by alcohol misuse. This report details secondary data analyses aggregating treatment-seeking samples across ten NIDA Clinical Trials Network treatment trials to examine alcohol-related characteristics of opiate-primary (OP) clients and compare broad pre-treatment characteristics of those with and without an alcohol use disorder (AUD). Analysis of this aggregate OP client sample (N=1397) indicated that 38% had comorbid AUD, and that a history of alcohol treatment episodes and recent alcohol problems were common. Further, comparisons of OP clients with and without AUD revealed the former were more likely to have had a history of pervasive difficulties in psychosocial functioning. Findings suggest need for detection of and intervention for alcohol misuse at the outset of opiate treatment, and support the practice of availing medical, psychological, case management, and other support services.
The current study was designed to re-examine the motivation matching hypothesis from Project MATCH using growth mixture modeling, an analytical technique that models variation in individual drinking patterns.
Design, setting and participants
Secondary data analyses of data from Project MATCH (n = 1726), a large multi-site alcoholism treatment-matching study.
Percentage of drinking days was the primary outcome measure, assessed from 1 month to 12 months following treatment. Treatment assignment, alcohol dependence symptoms and baseline percentage of drinking days were included as covariates.
The results provided support for the motivation matching hypothesis in the out-patient sample and among females in the aftercare sample: the majority of individuals with lower baseline motivation had better outcomes if assigned to motivation enhancement treatment (MET) compared to those assigned to cognitive behavioral treatment (CBT). In the aftercare sample there was a moderating effect of gender and alcohol dependence severity, whereby males with lower baseline motivation and greater alcohol dependence drank more frequently if assigned to MET compared to those assigned to CBT.
Results from the current study lend partial support to the motivation-matching hypothesis and also demonstrated the importance of moderating influences on treatment matching effectiveness. Based upon these findings, individuals with low baseline motivation in out-patient settings and males with low levels of alcohol dependence or females in aftercare settings may benefit more from motivational enhancement techniques than from cognitive–behavioral techniques.
Client–treatment-matching; cognitive–behavioral therapy; growth mixture modeling; motivation to change; motivational enhancement therapy; Project MATCH