Opening the "black box": Four common implementation strategies for expanding the use of medications for opioid use disorder in primary care.

Background: Despite the persistent increase in overdose deaths, access to medications for opioid use disorders remains limited. Recent federal funding aimed at increasing access prompts a need to understand if implementation strategies improve access. Methods: This is an analysis of data from 174 primary care clinics enrolled in a state-wide medications for opioid use disorders (MOUD) implementation effort in California. We examined clinic use of one of four implementation strategies: learning collaboratives, Project Extension for Community Health care Outcomes (ECHO), didactic webinars, and clinical skills trainings. The primary implementation outcome was categorical change in new patients prescribed buprenorphine. Univariate and multivariate logistic regressions were used to determine the impact of clinic attendance in all or individual implementation strategies, respectively, on patient growth. Results: Clinics attending learning collaboratives, Project ECHO, and clinical skills trainings had significantly higher odds of patient growth (odds ratio [OR] = 3.56; 95% confidence interval [CI] = 1.78, 7.10, p < .001), (OR = 3.39; 95% CI = 1.59, 7.24, p < .01), (OR = 3.90, 95% CI = 1.64, 9.23, p < .01) than non-attending clinics. The impact of attendance at learning collaboratives (OR = 5.81, 95% CI = 1.89, 17.85; p < .01), didactic webinars (OR = 3.59; 95% CI = 1.04, 12.35; p < .05), and clinical skills trainings (OR = 3.53, 95% CI = 1.06, 11.78, p < .05) on patient growth was greater for Federally Qualified Health Centers. When comparing strategies in multivariate models, only the relationship between learning collaborative attendance and new patients prescribed buprenorphine remained significant (OR = 2.57; 95% CI = 1.12, 5.88; p < .05). Conclusions: This study reported on a large, statewide, implementation-as-usual project offering four typical implementation strategies. Clinic attendance at learning collaboratives, a multi-component strategy, had the most consistent impact on new patients prescribed buprenorphine. These results suggest that while a broad array of strategies was initially reasonable, optimizing the selection of implementation strategies could be more effective. Plain Language Summary: Access to life-saving medications for opioid use disorder, such as buprenorphine, remains limited despite strong evidence of effectiveness. Systems and organizations often select from a variety of implementation strategies aimed at expanding access to these medications. However, scant research exists to enable these organizations to select the most effective and efficient strategies. Our study-within a large state-wide system of care-examined the impact of primary care clinic attendance in four common implementation strategies on new patients prescribed buprenorphine. Learning collaboratives were the strategy that most consistently improved outcomes. These results highlight the challenges to strategy selection inherent in implementation-as-usual systems-level approaches. The field needs evidence-based information on which implementation strategies are most likely to yield desired implementation outcomes.

Implementation of the hub and spoke model for opioid use disorders in California: Rationale, design and anticipated impact.

As part of the State Targeted Response to the opioid epidemic, California has adopted the Hub and Spoke model to expand access to medications for opioid use disorder, particularly buprenorphine, throughout the state. By aligning opioid treatment programs as hubs with primary care, office-based practitioners, and other health care settings as spokes, a broader treatment model can reach more people with opioid use disorder, improve access to medications for opioid use disorders, and decrease overdose deaths. Expanding access requires expanding knowledge and intensive implementation support of new practices. This paper describes the rationale, specific activities and anticipated impact of the implementation plan in California's Hub and Spoke system. Training and technical assistance are designed to: increase the number and capacity of waivered prescribers; enhance skills of prescribers and multidisciplinary teams; and create systems change. Activities include buprenorphine waiver trainings and provider support, a practice facilitator program, Project ECHO sessions, webinars, clinical skills trainings, and regional learning collaboratives. This overview highlights the steps California is taking to build treatment capacity to address the opioid epidemic.

Using e-technologies in clinical trials.

Clinical trials have been slow to incorporate e-technology (digital and electronic technology that utilizes mobile devices or the Internet) into the design and execution of studies. In the meantime, individuals and corporations are relying more on electronic platforms and most have incorporated such technology into their daily lives. This paper provides a general overview of the use of e-technologies in clinical trials research, specifically within the last decade, marked by rapid growth of mobile and Internet-based tools. Benefits of and challenges to the use of e-technologies in data collection, recruitment and retention, delivery of interventions, and dissemination are provided, as well as a description of the current status of regulatory oversight of e-technologies in clinical trials research. As an example of ways in which e-technologies can be used for intervention delivery, a summary of e-technologies for treatment of substance use disorders is presented. Using e-technologies to design and implement clinical trials has the potential to reach a wide audience, making trials more efficient while also reducing costs; however, researchers should be cautious when adopting these tools given the many challenges in using new technologies, as well as threats to participant privacy/confidentiality. Challenges of using e-technologies can be overcome with careful planning, useful partnerships, and forethought. The role of web- and smartphone-based applications is expanding, and the increasing use of those platforms by scientists and the public alike make them tools that cannot be ignored.

The Use of Technology in Participant Tracking and Study Retention: Lessons Learned From a Clinical Trials Network Study.

BACKGROUND: The growing use of newer communication and Internet technologies, even among low-income and transient populations, require research staff to update their outreach strategies to ensure high follow-up and participant retention rates. This paper presents the views of research assistants on the use of cell phones and the Internet to track participants in a multisite randomized trial of substance use disorder treatment. METHODS: Preinterview questionnaires exploring tracking and other study-related activities were collected from 21 research staff across the 10 participating US sites. Data were then used to construct a semistructured interview guide that, in turn, was used to interview 12 of the same staff members. The questionnaires and interview data were entered in Atlas.ti and analyzed for emergent themes related to the use of technology for participant-tracking purposes. RESULTS: Study staff reported that most participants had cell phones, despite having unstable physical addresses and landlines. The incoming call feature of most cell phones was useful for participants and research staff alike, and texting proved to have additional benefits. However, reliance on participants' cell phones also proved problematic. Even homeless participants were found to have access to the Internet through public libraries and could respond to study staff e-mails. Some study sites opened generic social media accounts, through which study staff sent private messages to participants. However, the institutional review board (IRB) approval process for tracking participants using social media at some sites was prohibitively lengthy. Internet searches through Google, national paid databases, obituaries, and judiciary Web sites were also helpful tools. CONCLUSIONS: Research staff perceive that cell phones, Internet searches, and social networking sites were effective tools to achieve high follow-up rates in drug abuse research. Studies should incorporate cell phone, texting, and social network Web site information on locator forms; obtain IRB approval for contacting participants using social networking Web sites; and include Web searches, texting, and the use of social media in staff training as standard operating procedures.

Gender-based Outcomes and Acceptability of a Computer-assisted Psychosocial Intervention for Substance Use Disorders.

BACKGROUND: Digital technologies show promise for increasing treatment accessibility and improving quality of care, but little is known about gender differences. This secondary analysis uses data from a multi-site effectiveness trial of a computer-assisted behavioral intervention, conducted within NIDA's National Drug Abuse Clinical Trials Network, to explore gender differences in intervention acceptability and treatment outcomes. METHODS: Men (n=314) and women (n=192) were randomly assigned to 12-weeks of treatment-as-usual (TAU) or modified TAU+Therapeutic Education System (TES), whereby TES substituted for 2hours of TAU per week. TES is composed of 62 Web-delivered, multimedia modules, covering skills for achieving and maintaining abstinence plus prize-based incentives contingent on abstinence and treatment adherence. Outcomes were: (1) abstinence from drugs and heavy drinking in the last 4weeks of treatment, (2) retention, (3) social functioning, and (4) drug and alcohol craving. Acceptability was the mean score across five indicators (i.e., interesting, useful, novel, easy to understand, and satisfaction). RESULTS: Gender did not moderate the effect of treatment on any outcome. Women reported higher acceptability scores at week 4 (p=.02), but no gender differences were detected at weeks 8 or 12. Acceptability was positively associated with abstinence, but only among women (p=.01). CONCLUSIONS: Findings suggest that men and women derive similar benefits from participating in a computer-assisted intervention, a promising outcome as technology-based treatments expand. Acceptability was associated with abstinence outcomes among women. Future research should explore characteristics of women who report less satisfaction with this modality of treatment and ways to improve overall acceptability.

Acceptability of a web-based community reinforcement approach for substance use disorders with treatment-seeking American Indians/Alaska Natives.

Longstanding disparities in substance use disorders and treatment access exist among American Indians/Alaska Natives (AI/AN). Computerized, web-delivered interventions have potential to increase access to quality treatment and improve patient outcomes. Prior research supports the efficacy of a web-based version [therapeutic education system (TES)] of the community reinforcement approach to improve outcomes among outpatients in substance abuse treatment; however, TES has not been tested among AI/AN. The results from this mixed method acceptability study among a diverse sample of urban AI/AN (N = 40) show that TES was acceptable across seven indices (range 7.8-9.4 on 0-10 scales with 10 indicating highest acceptability). Qualitative interviews suggest adaptation specific to AI/AN culture could improve adoption. Additional efforts to adapt TES and conduct a larger effectiveness study are warranted.

Racial/ethnic match and treatment outcomes for women with PTSD and substance use disorders receiving community-based treatment.

This study examined the relationship between racial/ethnic match and treatment outcomes for 224 women who participated in a clinical trial of group treatments for posttraumatic stress disorder (PTSD) and substance use disorders. Generalized estimating equations were used to examine the effect of client-therapist racial/ethnic match on outcomes. Results revealed racial/ethnic match was not significantly associated with session attendance. There was a significant three-way interaction between client race/ethnicity, baseline level of PTSD symptoms, and racial/ethnic match on PTSD outcomes. White clients, with severe PTSD symptoms at baseline, who attended treatment groups where they were matched with their therapist, had greater reductions in PTSD symptoms at follow-up than their counterparts who were racially/ethnically mismatched with their group therapist. Racial/ethnic match did not confer additional benefits for Black clients in terms of PTSD outcomes. Racial/ethnic match interacted with baseline substance use to differentially influence substance use outcomes at follow-up for all women. Clinical implications are discussed.

Internet-delivered treatment for substance abuse: a multisite randomized controlled trial.

OBJECTIVE: Computer-delivered interventions have the potential to improve access to quality addiction treatment care. The objective of this study was to evaluate the effectiveness of the Therapeutic Education System (TES), an Internet-delivered behavioral intervention that includes motivational incentives, as a clinician-extender in the treatment of substance use disorders. METHOD: Adult men and women (N=507) entering 10 outpatient addiction treatment programs were randomly assigned to receive 12 weeks of either treatment as usual (N=252) or treatment as usual plus TES, with the intervention substituting for about 2 hours of standard care per week (N=255). TES consists of 62 computerized interactive modules covering skills for achieving and maintaining abstinence, plus prize-based motivational incentives contingent on abstinence and treatment adherence. Treatment as usual consisted of individual and group counseling at the participating programs. The primary outcome measures were abstinence from drugs and heavy drinking (measured by twice-weekly urine drug screens and self-report) and time to dropout from treatment. RESULTS: Compared with patients in the treatment-as-usual group, those in the TES group had a lower dropout rate (hazard ratio=0.72, 95% CI=0.57, 0.92) and a greater abstinence rate (odds ratio=1.62, 95% CI=1.12, 2.35). This effect was more pronounced among patients who had a positive urine drug or breath alcohol screen at study entry (N=228) (odds ratio=2.18, 95% CI=1.30, 3.68). CONCLUSIONS: Internet-delivered interventions such as TES have the potential to expand access and improve addiction treatment outcomes. Additional research is needed to assess effectiveness in non-specialty clinical settings and to differentiate the effects of the community reinforcement approach and contingency management components of TES.

Web-based, psychosocial treatment for substance use disorders in community treatment settings.

The purpose of this multisite clinical trial was to evaluate the effectiveness of a web-based version of the Community Reinforcement Approach, plus motivational incentives, within community-based, outpatient substance abuse treatment. This ongoing study is being conducted within the National Drug Abuse Treatment Clinical Trials Network, funded by the National Institute on Drug Abuse. Midway through the enrollment of 500 participants, the study is being implemented in 10 treatment programs across the United States. Information is provided on design, sample, intervention and technology, and preliminary lessons learned.

Helping alliance, retention, and treatment outcomes: a secondary analysis from the NIDA Clinical Trials Network Women and Trauma Study.

We examined the association between the therapeutic alliance and treatment outcomes among 223 women with posttraumatic stress disorder (PTSD) and substance use disorders who participated in a multisite clinical trial of group treatments for trauma and addictions in the United States throughout 2004 and 2005. General linear models indicated that women who received Seeking Safety, a cognitive-behavioral treatment, had significantly higher alliance ratings than those in Women's Health Education, a control group. Alliance was related to significant decreases in PTSD symptoms and higher attendance in both interventions. Alliance was not related to substance use outcomes. Implications and limitations of the findings are discussed.

Design and methodological considerations of an effectiveness trial of a computer-assisted intervention: an example from the NIDA Clinical Trials Network.

Computer-assisted interventions hold the promise of minimizing two problems that are ubiquitous in substance abuse treatment: the lack of ready access to treatment and the challenges to providing empirically-supported treatments. Reviews of research on computer-assisted treatments for mental health and substance abuse report promising findings, but study quality and methodological limitations remain an issue. In addition, relatively few computer-assisted treatments have been tested among illicit substance users. This manuscript describes the methodological considerations of a multi-site effectiveness trial conducted within the National Institute on Drug Abuse's (NIDA's) National Drug Abuse Treatment Clinical Trials Network (CTN). The study is evaluating a web-based version of the Community Reinforcement Approach, in addition to prize-based contingency management, among 500 participants enrolled in 10 outpatient substance abuse treatment programs. Several potential effectiveness trial designs were considered and the rationale for the choice of design in this study is described. The study uses a randomized controlled design (with independent treatment arm allocation), intention-to-treat primary outcome analysis, biological markers for the primary outcome of abstinence, long-term follow-up assessments, precise measurement of intervention dose, and a cost-effectiveness analysis. Input from community providers during protocol development highlighted potential concerns and helped to address issues of practicality and feasibility. Collaboration between providers and investigators supports the utility of infrastructures that enhance research partnerships to facilitate effectiveness trials and dissemination of promising, technologically innovative treatments. Outcomes from this study will further the empirical knowledge base on the effectiveness and cost-effectiveness of computer-assisted treatment in clinical treatment settings.

NIDA's Clinical Trials Network: an opportunity for HIV research in community substance abuse treatment programs.

BACKGROUND/OBJECTIVES: 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 activities of the CTN during its first 10 years. RESULTS: 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. CONCLUSION/SIGNIFICANCE: 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.

Gender research in the National Institute on Drug Abuse National Treatment Clinical Trials Network: a summary of findings.

BACKGROUND: The National Institute of Drug Abuse's National Drug Abuse Treatment Clinical Trials Network (CTN) was established to foster translation of research into practice in substance abuse treatment settings. The CTN provides a unique opportunity to examine in multi-site, translational clinical trials, the outcomes of treatment interventions targeting vulnerable subgroups of women; the comparative effectiveness of gender-specific protocols to reduce risk behaviors; and gender differences in clinical outcomes. OBJECTIVES: To review gender-related findings from published CTN clinical trials and related studies from January 2000 to March 2010. METHODS: CTN studies were selected for review if they focused on treatment outcomes or services for special populations of women with substance use disorders (SUDs) including those with trauma histories, pregnancy, co-occurring eating and other psychiatric disorders, and HIV risk behaviors; or implemented gender-specific protocols. The CTN has randomized 11,500 participants (41% women) across 200 clinics in 24 randomized controlled trials in community settings, of which 4 have been gender-specific. RESULTS: This article summarizes gender-related findings from CTN clinical trials and related studies, focusing on trauma histories, pregnancy, co-occurring eating and other psychiatric disorders, and HIV risk behaviors. CONCLUSIONS: These published studies have expanded the evidence base regarding interventions for vulnerable groups of women with SUDs as well as gender-specific interventions to reduce HIV risk behaviors in substance-using men and women. The results also underscore the complexity of accounting for gender in the design of clinical trials and analysis of results. SCIENTIFIC SIGNIFICANCE: To fully understand the relevance of gender-specific moderators and mediators of outcome, it is essential that future translational studies adopt more sophisticated approaches to understanding and measuring gender-relevant factors and plan sample sizes that are adequate to support more nuanced analytic methods.

Baseline matters: the importance of covariation for baseline severity in the analysis of clinical trials.

BACKGROUND: Clinical trials testing the effectiveness of interventions for addictions, HIV transmission risk, and other behavioral health problems are important to advancing evidence-based treatment. Such trials are expensive and time-consuming to conduct, but the underlying effect sizes tend to be modest, and often findings are disappointing, failing to show evidence of treatment effects. OBJECTIVES: To demonstrate how appropriate covariation for baseline severity can enhance detection of treatment effects. METHODS: Explication and case example. RESULTS: Baseline severity (the score of the outcome measure at baseline, prior to randomization) is often strongly associated with outcome in such studies. Covariation for baseline score may enhance detection of treatment effects, because the variance explained by the baseline score is removed from the error variance in the estimate of the difference in outcome between treatments. Alternatively, the effect of treatment may manifest in the form of a baseline-by-treatment interaction. Common interaction patterns include that treatment may be more effective among patients with higher levels of baseline severity, or treatment may be more effective among patients with low severity at baseline ('relapse prevention' effect). Such effects may be important to developing treatment guidelines and offer clues toward understanding the mechanisms of action of treatments and of the disorders. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This article illustrates principles of covariation for baseline and the baseline-by-treatment interaction in nontechnical graphical terms, and discusses examples from clinical trials. Implications for the design and analysis of clinical trials are discussed, and it is argued that covariation for baseline severity of the outcome measure and testing of the baseline-by-treatment interaction should be considered for inclusion in the primary outcome analyses of treatment effectiveness trials of substantial size.

Community Providers' Impression of HIV Prevention Intervention Research in NIDA's Clinical Trials Network.

Research-based approaches to HIV risk reduction are available but not readily adopted by community-based treatment programs. This exploratory survey study assessed staff (N=116) attitudes as a function of direct research participation, treatment program type, and study performance within seven methadone maintenance and eight psychosocial outpatient substance abuse treatment programs that participated in the NIDA Clinical Trials Network HIV risk reduction trials. Clinical staff who directly participated in the research reported intervention components as useful and were more likely to report perceived increases in HIV testing/referrals compared to staff who did not directly participate. However, those directly involved reported less positive attitudes about clinical impact and research impression. Results suggest a positive influence of research participation on awareness of program services, but also the need to address practical and professional issues related to research collaboration. Effectiveness trials offer a valuable opportunity to assess provider-level factors associated with adoption and implementation.

Do treatment improvements in PTSD severity affect substance use outcomes? A secondary analysis from a randomized clinical trial in NIDA's Clinical Trials Network.

OBJECTIVE: The purpose of the analysis was to examine the temporal course of improvement in symptoms of posttraumatic stress disorder (PTSD) and substance use disorder among women in outpatient substance abuse treatment. METHOD: Participants were 353 women randomly assigned to 12 sessions of either trauma-focused or health education group treatment. PTSD and substance use assessments were conducted during treatment and posttreatment at 1 week and after 3, 6, and 12 months. A continuous Markov model was fit on four defined response categories (nonresponse, substance use response, PTSD response, or global response [improvement in both PTSD and substance use]) to investigate the temporal association between improvement in PTSD and substance use symptom severity during the study's treatment phase. A generalized linear model was applied to test this relationship over the follow-up period. RESULTS: Subjects exhibiting nonresponse, substance use response, or global response tended to maintain original classification; subjects exhibiting PTSD response were significantly more likely to transition to global response over time, indicating maintained PTSD improvement was associated with subsequent substance use improvement. Trauma-focused treatment was significantly more effective than health education in achieving substance use improvement, but only among those who were heavy substance users at baseline and had achieved significant PTSD reductions. CONCLUSIONS: PTSD severity reductions were more likely to be associated with substance use improvement, with minimal evidence of substance use symptom reduction improving PTSD symptoms. Results support the self-medication model of coping with PTSD symptoms and an empirical basis for integrated interventions for improved substance use outcomes in patients with severe symptoms.

The impact of trauma-focused group therapy upon HIV sexual risk behaviors in the NIDA Clinical Trials Network "Women and trauma" multi-site study.

Women in drug treatment struggle with co-occurring problems, including trauma and post-traumatic stress disorder (PTSD), which can heighten HIV risk. This study examines the impact of two group therapy interventions on reduction of unprotected sexual occasions (USO) among women with substance use disorders (SUD) and PTSD. Participants were 346 women recruited from and receiving treatment at six community-based drug treatment programs participating in NIDA's Clinical Trials Network. Participants were randomized to receive 12-sessions of either seeking safety (SS), a cognitive behavioral intervention for women with PTSD and SUD, or women's health education (WHE), an attention control psychoeducational group. Participants receiving SS who were at higher sexual risk (i.e., at least 12 USO per month) significantly reduced the number of USO over 12-month follow up compared to WHE. High risk women with co-occurring PTSD and addiction may benefit from treatment addressing coping skills and trauma to reduce HIV risk.

Multisite randomized trial of behavioral interventions for women with co-occurring PTSD and substance use disorders.

The authors compared the effectiveness of the Seeking Safety group, cognitive-behavioral treatment for substance use disorder and posttraumatic stress disorder (PTSD), to an active comparison health education group (Women's Health Education [WHE]) within the National Institute on Drug Abuse's Clinical Trials Network. The authors randomized 353 women to receive 12 sessions of Seeking Safety (M = 6.2 sessions) or WHE (M = 6.0 sessions) with follow-up assessment 1 week and 3, 6, and 12 months posttreatment. Primary outcomes were the Clinician Administered PTSD Scale (CAPS), the PTSD Symptom Scale-Self Report (PSS-SR), and a substance use inventory (self-reported abstinence and percentage of days of use over 7 days). Intention-to-treat analysis showed large, clinically significant reductions in CAPS and PSS-SR symptoms (d = 1.94 and 1.12, respectively) but no reliable difference between conditions. Substance use outcomes were not significantly different over time between the two treatments and at follow-up showed no significant change from baseline. Study results do not favor Seeking Safety over WHE as an adjunct to substance use disorder treatment for women with PTSD and reflect considerable opportunity to improve clinical outcomes in community-based treatments for these co-occurring conditions.