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Given the disproportionate impact of substance use on individuals, families, and communities from populations underrepresented in clinical trials, increasing their enrollment in treatment research is critical for ensuring that the findings inform policies and programs that are inclusive of all communities, thereby advancing health equity. However, since underrepresented groups continue to be underenrolled in clinical trials testing the efficacy and effectiveness of psychosocial treatments for substance use disorder, substance use researchers are still grappling with this challenge.

In this commentary, we describe rigorous methodological approaches, such as integrative data analysis (IDA) and related methods (e.g., moderated nonlinear factor analysis and propensity score weighting), that can help address the challenges posed by the underrepresentation of certain populations. By combining individual-level data from multiple studies into a pooled dataset, these methods increase sample size and statistical power while addressing covariate imbalance across treatment groups. We describe how we employed these methods to address the aims of our recently completed secondary data analysis project conducted within the National Drug Abuse Treatment Clinical Trial Network (CTN-0125; Integrative Data Analysis of CTN Studies to Examine the Impact of Psychosocial Treatments for Black People Who Use Cocaine and/or Opioids). Our study used these methods to pool and analyze data from nine completed CTN trials to assess the comparative effectiveness of psychosocial treatments for Black adults who use cocaine and/or opioids, a group underrepresented in registered trials of the NIDA. We illustrate the application of these methodological approaches in CTN-0125 and demonstrate how they complement each other to address unique analytic challenges. We describe how we addressed data harmonization challenges due to variations in data formats and inconsistencies or gaps in the supportive documentation available on the NIDA Data Share website. We conclude with recommendations for the research field on how to further address sample size and data integration challenges.

Related protocols: CTN-0125

This commentary examines methodological and ethical problems encountered when a multi-arm clinical trial loses access to one or more of its arms, using the Retention Phase of the NIDA Clinical Trials Network CTN-0100 study, Optimizing Retention, Duration and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy (RDD) as an example.

RDD is a community-based, multi-site trial testing strategies to reduce dropout from medication treatment for opioid use disorder. Among patients with opioid use disorder initiating buprenorphine treatment, the original design was a 3 by 2 factorial comprising 3 pharmacological conditions (Standard-Dose sublingual buprenorphine–16 mg/day target [SL-BUP 16], High-Dose sublingual buprenorphine–32 mg/day target [SL-BUP 32], or extended-release injectable buprenorphine [XR-BUP]), crossed with 2 behavioral conditions: medical management with vs. without a technology-based digital therapeutic app providing cognitive behavioral therapy lessons and contingency management.

The trial experienced two major disruptions to study interventions: 1) The supply of XR-BUP became temporarily unavailable due to manufacturing problems; and 2) The company supplying the digital therapeutic app went bankrupt, rendering the original app permanently unavailable. Questions considered by the study lead team included: 1) Whether to pause recruitment into the trial altogether or continue recruitment into truncated designs omitting the unavailable interventions; 2) How to account for participants who did not experience full exposure to the halted interventions; 3) Whether to substitute a similar intervention; and 4) The problem of concurrent randomizations, namely that a truncated design does not contain all the concurrent randomizations of the full design, introducing risk of confounding or bias.

This experience from the RDD trial demonstrates how multi-arm clinical trials that lose access to an intervention arm can continue with a truncated design, allowing continued progress on study aims, while balancing methodological purity with the pragmatic imperative to keep the trial running and respect subjects’ participation.

Related protocols: CTN-0100

This is the primary outcomes article for CTN-0083.

Social media sites, dating apps, and information search sites have been used to reach individuals at high risk for HIV infection. However, it is not clear which platform is the most efficient in promoting home HIV self-testing, given that the users of various platforms may have different characteristics that impact their readiness for HIV testing.

This study, CTN-0083, “Using Social Media to Deliver HIV Self-Testing Kits and Link to Online PrEP Services,” aimed to compare the relative effectiveness of social media sites, dating apps, and information search sites in promoting HIV self-testing among minority men who have sex with men (MSM) at an increased risk of HIV infection. Test kit order rates were used as a proxy to evaluate promotion effectiveness. In addition, researchers assessed differences in characteristics between participants who ordered and did not order an HIV test kit.

Culturally appropriate advertisements were placed on popular sites of three different platforms: social media sites (Facebook, Instagram), dating apps (Grindr, Jack’D), and information search sites (Google, Bing). Advertisements targeted young (18-30 years old) and minority (Black or Latinx) MSM at risk of HIV exposure. Recruitment occurred in 2 waves, with each wave running advertisements on 1 platform of each type over the same period. Participants completed a baseline survey assessing sexual or injection use behavior, substance use including alcohol, psychological readiness to test, attitudes toward HIV testing and treatment, and HIV-related stigma. Participants received an electronic code to order a free home-based HIV self-test kit. Follow-up assessments were conducted to assess HIV self-test kit use and uptake of pre-exposure prophylaxis (PrEP) at 14 and 60 days post enrollment.

In total, 271 participants were enrolled, and 254 were included in the final analysis. Among these 254 participants, 177 (69.7%) ordered a home HIV self-test kit. Most of the self-test kits were ordered by participants enrolled from dating apps. Due to waves with low enrollment, between wave statistical comparisons were not feasible. Within wave comparison revealed that Jack’D showed higher order rates (3.29 kits/day) compared to Instagram (0.34 kits/day) and Bing (0 kits/day). There were no associations among self-test kit ordering and HIV-related stigma, perceptions about HIV testing and treatment, and mistrust of medical organizations.

Conclusions: These findings show that using popular dating apps might be an efficient way to promote HIV self-testing. Stigma, perceptions about HIV testing and treatment, or mistrust of medical organizations may not affect order rates of HIV test kits promoted on the internet.

Related protocols: CTN-0083

CHOICES, CTN-0067, was an open-label, randomized, comparative effectiveness trial of office-based extended-release naltrexone versus treatment as usual in people with untreated opioid use disorder and HIV. This study explored facilitators to recruitment in Miami, a successful recruiting site in the national trial. The mixed-methods study included quantitative surveys of randomized participants, medical record abstraction, and qualitative interviews with study staff. Miami recruited 47 (40.5%) of 116 randomized participants in the six-site national trial. In-depth interviews of study staff (n=6) revealed that Miami had a recruitment approach consisting of street level outreach and a close relationship with the local syringe services program (SSP). Partnership with a local SSP provided access to people living with HIV who inject drugs in Miami.

Conclusions: SSPs’ fundamental trust within the community of people who inject drugs can be leveraged in studies aiming to improve health outcomes in this underserved and high priority population.

Related protocols: CTN-0067

The majority of those living with HIV are men who have sex with men (MSM), and young, minority MSM account for more new HIV infections than any other group. HIV transmission can be reduced through detection and early treatment initiation, or starting pre-exposure prophylaxis (PrEP), but rates of testing are lower than recommended among MSM and PrEP uptake has been slow. Although promoting HIV testing and PrEP uptake by placing advertisements on web-based platforms — such as social media websites and dating apps — is a promising approach for promoting HIV testing and PrEP, the relative effectiveness of HIV prevention advertising on common web-based platforms is underexamined.

This study, protocol CTN-0083, Social Media to Deliver HIV Self-Testing Kits and Link to Online PrEP Services, aims to evaluate the relative effectiveness of advertisements place on three types of web-based platforms (social media websites, dating apps, and informational websites) for promoting HIV self-testing and PrEP uptake.

Advertisements will be placed on social media websites (Facebook, Instagram, and Twitter), dating apps (Grindr, Jack’d, Hornet), and informational search websites (Google, Yahoo, Bing) to recruit approximately 400 young (18-30 years), minority (Black/Latino) MSM at elevated risk of HIV exposure. Recruitment will occur in three waves, with each wave running advertisements on one website from each platform. The number of participants per platform is not pre-specified, and recruitment in each wave will occur until approximately 133 HIV self-tests are ordered. Participants will complete a baseline survey assessing risk behavior, substance use, psychological readiness to test, and attitudes and then receive an electronic code to order a free home-based HIV self-test kit. Two follow-ups are planned to assess HIV self-test result and PrEP uptake.

Recruitment is in progress and is anticipated to be completed by Fall 2020.

Conclusions: Findings may improve our understanding of how the platform users’ receptivity to test for HIV differs across web-based platforms and thus may assist in facilitating web-based HIV prevention campaigns.

Related protocols: CTN-0083

The National Drug Abuse Treatment Clinical Trials Network (CTN) was initiated by the National Institute on Drug Abuse (NIDA) in 2000 with the aim of improving substance use treatment and reducing the time between the discovery of effective treatments and their implementation into clinical practice. While initial trials were conducted almost exclusively in specialty addiction treatment settings, the CTN began evolving strategically in 2010 to conduct research in general medical settings, including healthcare systems, primary care settings, emergency departments, and pharmacies, to broaden impact. The advantages of a research network like the CTN is not only the collective content expertise that investigators contribute to the network, but the collective experience gained by conducting studies in the network and then applying those lessons to future studies.

This study aimed to summarize trial implementation challenges encountered, and the process by which solutions were identified and implemented, within one of the last early-phase CTN Stage II behavioral intervention studies conducted in a specialty addiction treatment setting, CTN-0037, the Stimulant Reduction Intervention Using Dosed Exercise (STRIDE) trial.

Issues encountered during study implementation are categorized into four major areas, described in terms useful to future study teams: 1) study team infrastructure challenges, 2) participant- and site- level challenges, 3) intervention-related challenges, and 4) longitudinal study design challenges. Potential consequences of identified problems and the solutions developed to manage these problems are discussed within the context of these four areas. The authors propose how to extend these implementation lessons and apply them in other healthcare settings to expand the CTN.

Conclusions: Effective study management allows for flexible, collaborative solutions to expected and unexpected obstacles to study success. Implementation strategies derived from the first 15 to 20 years of CTN studies are a result of working with providers and participants, and the ongoing collaboration among CTN investigators and network staff. Timely identification and response to problems during study implementation are critical to the success of a trial, regardless of its design. We believe a collaborative approach to identifying and responding to study implementation challenges will increase the likelihood of successful adoption of relevant, efficacious interventions. As the CTN continues to expand, the wealth of successful trial implementation strategies developed during the first 20 years of the CTN need to be applied and adapted to studies in broader network settings, and considered in conjunction with more formalized implementation science processes that are currently available.

Related protocols: CTN-0037

The application of digital technologies to better assess, understand, and treat substance use disorders (SUDs) is a particularly promising and vibrant area of scientific research. The National Drug Abuse Treatment Clinical Trials Network (CTN), launched in 1999 by the U.S. National Institute on Drug Abuse, has supported a growing line of research that leverages digital technologies to glean new insights into SUDs and provide science-based therapeutic tools to a diverse array of persons with SUDs.

This article provides an overview of the breadth and impact of research conducted in the realm of digital health within the CTN. This work has included the CTN’s efforts to systematically embed digital screeners for SUDs into general medical settings to impact care models across the nation. This work has also included a pivotal multi-site clinical trial conducted on the CTN platform, whose data led to the very first “prescription digital therapeutic” authorized by the U.S. Food and Drug Administration (FDA) for the treatment of SUDs. Further CTN research includes the study of telehealth to increase capacity for science-based SUD treatment in rural and under-resourced communities. In addition, the CTN has supported an assessment of the feasibility of detecting cocaine-taking behavior via smartwatch sensing. And, the CTN has supported the conduct of clinical trials entirely online (including the recruitment of national and hard-to-reach/under-served participant samples online, with remote intervention delivery and data collection). Further, the CTN is supporting innovative work focused on the use of digital health technologies and data analytics to identify digital biomarkers and understand the clinical trajectories of individuals receiving medications for opioid use disorder (OUD).

This paper concludes by outlining the many potential future opportunities to leverage the unique national CTN research network to scale-up the science on digital health to examine optimal strategies to increase the reach of science-based SUD service delivery models both within and outside of healthcare.

Related protocols: CTN-0044, CTN-0059, CTN-0073-Ot, CTN-0076, CTN-0083, CTN-0084-A-2, CTN-0090, CTN-0095, CTN-0101, CTN-0102

There is growing concern regarding the generalizability of findings from randomized controlled trials (RCTs) of interventions for substance use disorders (SUDs). This study used a selection model approach to assess and improve the generalizability of an evaluation for a web-based SUD intervention by making the trial sample resemble the target population.

The sample of the web-based SUD intervention (Therapeutic Education System vs. treatment-as-usual; n=507) was compared with the target population of SUD treatment-seeking individuals from the Treatment Episodes Data Set-Admissions (TEDS-A). Using weights based on the probabilities of RCT participation, weighted treatment effects on retention and abstinence were computed.

Substantial differences between the RCT sample and the target population were demonstrated in significant difference in the mean propensity scores (1.62 standard deviations at p<.001). The population effect on abstinence (12 weeks and 6 months) was statistically insignificant after weighting the data with the generalizability weight.

Conclusions: Findings from this study provide insights into the differences between RCT participants of a web-based SUD intervention and the target population from recent years. The results of this study also indicate how poor sample representativeness of the RCT compared with the target population impacted the observed findings of the web-based SUD intervention. Given the great potential for scalability of web-based SUD interventions, the representativeness of the sample with regard to the target population of potential users for the intervention should be carefully considered. Additionally, with a careful consideration of the treatment effect modifiers which are over- or under-representing in RCTs, application of generalizability weights could be a potentially useful tool for assessing and improving the generalizability of the findings from RCTs when the RCT sample does not well-represent the target population.

Related protocols: CTN-0044

Clinical trials have been slow to incorporate e-technology (digital and electronic technology that utilizes mobile devices of the Internet) into the design and execution of studies. In the meantime, individuals and corporations/organizations are relying more on electronic platforms and most have incorporating such technology into their daily lives. This paper, written by five members of the NIDA Clinical Trials Network, 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 the treatment of substance use disorders is presented, including the Therapeutic Education System studied in protocol CTN-0044 of the NIDA Clinical Trials Network, making trials more efficient while also reducing costs. However, researchers should be cautious when adopting these tools given the many challenges in uses new technologies, as well as threats to participant privacy/confidentiality.

Conclusions: Challenges of using e-technologies in each stage of a clinical trial 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.

Related protocols: CTN-0044

In 2012, the CTN Web Seminar Series introduced research staff to the use of social media in trials and the tools available in the market. Building on that training, this 60-minute webinar, produced by the National Drug Abuse Treatment Clinical Trials Network (CTN) Clinical Coordinating Center for CTN members and the public, focuses on applying that knowledge and incorporating guidelines for use in clinical trials.

Objectives for this webinar include:

• Understanding organizational and IRB guidelines regarding the use of social media in the conduct of research.
• Learning how to use social media tools to recruit, engage, and follow-up with research participants.
• Reviewing what elements to consider when drafting a social media strategy for your research project.
• The target audience is research staff interested in using social media in the conduct of clinical trials.

Presented by Erin L. Winstanley, PhD (University of Cincinnati, OV Node) and Gloria M. Miele, PhD (Columbia University, GNY Node)

Additional Resources:

• Download slides (pdf)
• Social Media Resource Guide

This workshop, led by Carmen Rosa of NIDA’s Center for the Clinical Trials Network, featured three presentations focused on the use of various types of new media in the design and conduct of clinical trials. Over 82% of adults now use internet or email, including 53% of those age 65 and older. Additionally, 67% of online adults use social networking sites. Mobile devices such as smartphones, tablets, netbooks, and laptops are now a primary source of Internet connectivity, and 79% of cell phone owners say they use text messaging. As use of these tools continues to grow, exploring ways to put them to use in clinical trials seems increasingly relevant.

The first presentation, by Erin Winstanley, “Using New Media Tools in the Design and Conduct of Clinical Trials,” provided an overview of the concept of “new media” and ways it can be applied to research, including advertising of studies, recruiting/tracking participants, communicating with participants, and disseminating research findings. An introduction to Facebook and Twitter is provided, as well as a look at the use of blogs, Pinterest, and LinkedIn.

Gloria Miele presented on “Social Media Communication Strategy,” giving participants a look at ways to think about and draft policies regarding the use of social media in your study or workplace. A variety of legal considerations, as well as examples of using social media to recruit study participants is also provided. Sample IRB guidance is included, along with IRB Best Practices for using new media. The presentation ends with a case study based on CTN-0044 (“Web Delivery of Evidence-Based, Psychosocial Treatment for Substance Use Disorders”), which used social media platforms like Facebook, as well as email and texting, to contact and follow-up with participants.

The third presentation, by Lynn Simpson, was a demonstration of the variety of uses for “REDCap, Research Electronic Data Capture, A Data Management and Survey Tool.” REDCap is a web-based application designed to give researchers and clinicians the capacity to create and manage databases and surveys in order to support data capture for research.

Related protocols: CTN-0044

High retention rates are critical for successful clinical trials, but participants in clinical research on stimulant abuse have demonstrated variable attendance at intervention and research visits. This poster reports on an innovative recruitment technique used by study staff in the National Drug Abuse Treatment Clinical Trials Network protocol CTN-0037 (Stimulant Reduction Intervention Using Dose Exercise (STRIDE)) to address some of the reasons for decreased attendance and barriers to retention before they become an issue for study participants. Nicknamed the “Fireside Chat,” the STRIDE approach used a series of “warm, supportive” questions to open a conversation with potential study participants, with the aim of helping them make an informed decision in a relatively short amount of time whether or not to join the study. Questions in the “chat” focused on willingness to commit, importance of the research question to the participant, understanding the requirements of participation, specific barriers to attendance, clarification of the study interventions/condition preference, and relapse potential.

Anecdotally, one site noted retention improvements after the Fireside Chat was implemented, and participants often expressed appreciation for taking part in the Chat. Though improvements cannot be solely attributed to the technique, research team members reported that being able to refer back to the Fireside Chat with participants helped them more openly discuss barriers to continued study participation. Clinical research with ongoing participant contact should consider tailoring this approach to increase retention. Future investigation with this approach is advised.

Related protocols: CTN-0037

This is the Results Article for CTN-0038-Ot.

This study examined motivations and barriers to substance abuse treatment entry and treatment continuation among Asian Americans and Pacific Islander (AAPI) substance users. APPI substance users (N=61) were recruited from substance abuse treatment programs in California and Hawaii. Semi-structured interviews and interviewer-administered surveys assessed barriers and facilitators to entering substance abuse treatment.

Barriers included peer pressure, family influences, and fear of “losing face.” Facilitators included peer support, involvement in the criminal justice system, a perceived need for treatment, and culturally competent substance abuse treatment services. Family and peer influences may act as both facilitators and impediments. AAPI substance using populations face many of the same individual-level and structural and systems barriers to entry to treatment as other substance using populations. However, similar to other racial/ethnic minority groups, it is important to address cultural differences. It may be important to keep in mind the ideas of family harmony, solidarity, and subordination of individual goals for the sake of family goals while designing substance abuse treatments for this population. In addition, integrating culturally sensitive screening tools, brief interventions, and referral to substance abuse treatment in medical care settings and non-traditional settings (e.g., health fairs, community cultural celebrations) may increase the numbers of AAPIs who seek substance abuse treatment.

Related protocols: CTN-0038-Ot

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, there is much less evidence concerning the efficacy of such interventions for drug users presenting in EDs. This presentation describes the design of the National Drug Abuse Treatment Clinical Trials Network protocol “Screening Motivational Assessment and Referral to Treatment in Emergency Departments (SMART-ED)” (CTN-0047), with a focus on the screening, assessment, treatment conditions, and follow-up procedures. 1285 patients who screened positive for current problematic substance use were randomly assigned to: (1) Minimal screen only (MSO), (2) Screening, assessment, and referral to treatment (if indicated) (SAR); or (3) Screening, assessment, and referral plus a brief intervention (BI) with two telephone follow-up booster calls (BI-B). BI-B therapists received considerable training, ongoing supervision and formal fidelity monitoring. The three-arm design was implemented to control for assessment reactivity. Sites recruited an average of approximately 21 participants per site per month. Treatment exposure was nearly universal for the initial BI, but a significant number of participants could not be reached for one or both of the booster sessions. Although follow-up is ongoing, current rates of follow-up exceed those specified in the analysis plan.

Conclusions: The study was completed on time, with good treatment exposure, strong attention to treatment fidelity, and excellent follow-up rates. Study outcomes should provide strong evidence regarding the efficacy of this brief intervention strategy for drug users presenting in medical EDs.

Related protocols: CTN-0047

This 90-minute webinar, produced by the National Drug Abuse Treatment Clinical Trials Network (CTN) Clinical Coordinating Center for CTN members and the public, discusses social media, an innovative, effective medium to build relationships and remain connected with others. The webinar provides an overview of various social media tools, such as LinkedIn, Facebook, Twitter, Google+, and blogs. Additional guidance will be included regarding how to develop your social media strategies for client engagement and retention, dissemination of research findings, and building your professional network. A social media resource guide, developed by the Research Utilization Committee’s Social Media Workgroup, is also available.

The target audience is CTN members and other researchers and clinicians who are interested in learning more about the use of social media tools in research and clinical practice.

Presented by Meg Brunner, MLIS, and Erin L. Winstanely, PhD.

Additional Resources:

• Social Media Resource Guide, 2012 (CTN RUC) (pdf) | Download slides (pdf)