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This is the primary outcomes article for CTN-0080-A-2. Introduction: Racial and ethnic inequities persist in medication treatment initiation and adherence for pregnant and postpartum people with opioid use disorder (OUD). Our objective was to understand the experiences of “positive outliers,” specifically pregnant and postpartum people of color with OUD who utilized medication treatment and engaged in a randomized clinical trial for buprenorphine despite historical, cultural, and structural barriers.

Methods: We conducted two sets of semi-structured qualitative interviews. First, trained peers with lived expertise as mothers in recovery interviewed individuals who identified with a non-white race and/or ethnicity and enrolled in the Medication Treatment for OUD in Expectant Mothers (MOMs) trial (NCT03918850). Second, we interviewed principal investigators, clinicians, and research coordinators from the 13 MOMs trial sites. We used an inductive thematic approach informed by the Social Ecological Model of Racism and Anti-Racism. Transcripts were double-coded and reviewed until consensus was reached. Preliminary findings from participant and staff interviews were merged and triangulated with peers to inform theme development.

Results: We completed 17 interviews with MOMs trial participants from 7 sites. Participants identified as Hispanic (29%), Black non-Hispanic (24%), multi-racial Hispanic (18%), multi-racial non-Hispanic (18%), and American Indian, Native Hawaiian, or Pacific Islander (12%). Thirty-two interviews with trial staff were also completed. Three themes emerged: (1) Although some participants expected racist treatment and research exploitation, all participants interviewed reported non-discriminatory, non-judgmental care within the MOMs trial; (2) Compassionate care, frequent, personalized, and integrated encounters, and emotional support helped counteract prior stigmatizing and discriminatory health care interactions, enabling participants of color to feel particularly supported, trusted, and empowered during the MOMs trial; and (3) Despite pervasive cultural stigma around addiction and concerns about taking an investigational drug while pregnant, participants expressed that pregnancy status, care team trust, and transparent communication with MOMs trial staff encouraged medication utilization and adherence.

Conclusion: Facilitators of successful engagement in the MOMs trial and retention in medication treatment among pregnant and postpartum people of color with OUD included non-judgmental care, sustained trust, and frequent contact. Key perinatal OUD clinical interventions and trial improvements include personalized communication and scheduling flexibility to promote engagement of marginalized populations.

Related protocols: CTN-0080-A-2

Background and aims: Despite similar substance use levels, Black adults experience greater family, legal, employment and other social-contextual challenges related to recovery than other groups. Substance use treatments that address both substance use and social-contextual factors are uniquely positioned to address these substance-related problems and produce more sustainable improvements in social functioning than treatment as usual (TAU) or behavioral controls (Control). The aim of this study was to evaluate changes in substance-related problems among Black adults, focusing on the comparative effectiveness between social-contextual treatments and TAU/Control.

Design: Individual-level data synthesis based on secondary analysis of Black adults enrolled in the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN).

Setting: All data were collected in the primary studies between 2001 and 2008 at clinics across the United States.

Participants: Black adults who reported cocaine and/or opioid use across nine studies within the NIDA CTN. The sample used herein consisted of individuals from five of these studies who provided data on substance-related problems (n=532; mean age=39.34; standard deviation=9.6).

Measurements: There were two treatment conditions: Social-contextual (e.g. Motivational Interviewing, Seeking Safety, STAGE 12) and TAU/Control. Moderated nonlinear factor analysis estimated latent scores for substance-related problems, using subscales from the Addiction Severity Index, while accounting for measurement noninvariance across studies, time and covariates. Linear mixed models estimated latent score differences over time between social-contextual treatments and TAU/Control during treatment and from the end of treatment through 12-month follow-up.

Findings: Both treatment groups improved across substance-related problem areas from baseline to the end-of-treatment (Cohen’s d = -0.10 to d = -0.47), with effects maintained at 12-month follow-up. Although social-contextual treatments did not statistically significantly outperform TAU/Control from baseline to end-of-treatment, they showed greater effects from end of treatment to 12-month follow-up in family/social [Cohen’s d difference ( d) = -0.47, 95% confidence interval (CI) = -0.57 to -0.38], legal ( d = -0.20, 95% CI = -0.31 to -0.10) and psychiatric problems ( d = 0.29, 95% CI = -0.38 to -0.20) than TAU/Control. Sensitivity analyses indicated that Seeking Safety and STAGE 12 predominantly drove post-treatment improvements in family/social problems.

Conclusions: Substance use treatment may yield broader, delayed benefits beyond substance use reduction among Black adults in the United States. Compared with treatment-as-usual, social-contextual treatments can yield more sustainable effects in legal, family and psychiatric areas among Black adults, with interventions such as Seeking Safety and STAGE 12 showing particular benefits in addressing family-related challenges.

Related protocols: CTN-0125

Objectives: Racial and ethnic differences in long-term outcomes associated with medications for opioid use disorder (MOUD) are poorly understood.

Methods: The present analyses were based on 751 participants with opioid use disorder (OUD) who were initially recruited from opioid treatment programs located in California, Connecticut, Oregon, Pennsylvania, and Washington and participated in a randomized controlled trial and at least one follow-up interview. 9.6% (n=72) of the participants self-identified as Non-Hispanic (NH) Black, 16.0% (n=120) Hispanic, and 74.4% (n=559) NH White. We tested racial and ethnic differences in psychiatric or social functioning, substance use and treatment participation.

Results: From the baseline to the end of follow-up interview, compared with NH White, Hispanic participants had a significantly greater proportion of months reporting any opioid use (45.5% vs. 32.5%, p<0.001) and a smaller proportion of months receiving any MOUD (47.7% vs. 58.1%; p<0.05), particularly receipt of buprenorphine treatment (8.3% vs. 14.9%; p<0.01). At the third follow-up interview, data from the Addiction Severity Index (ASI) indicated that Hispanic participants had greater severity in employment problems (0.72 vs. 0.58; p < 0.001), while Black participants had less severity in drug problems (0.11 vs. 0.16; p<0.05) compared to NH Whites.

Conclusions: The study found that Hispanic participants had higher rates of opioid use (heroin and prescription opioids), but few received MOUD (buprenorphine and methadone) during the follow-up period, which suggests that effective strategies are needed to increase access to MOUD among Hispanics. Additionally, addressing employment challenges might also help improve long-term outcomes for all populations with OUD.

Related protocols: CTN-0050

Racial and ethnic disparities in access to treatment and quality of treatment for opioid use disorder (OUD) have been identified in usual care settings. In contrast, disparities in treatment quality within clinical trials are relatively unexamined. This study aimed to estimate racial and ethnic differences in the dose of opioid agonist treatment for OUD in the first 4 weeks of treatment in clinical trials.

This cohort study performed analysis of the methadone and buprenorphine treatment arms of 3 trials conducted by the National Institute on Drug Abuse Clinical Trials Network between May 2006, and January 31, 2017, at multiple Clinical Trials Network sites across the US (CTN-0027, START, CTN-0030, POATS, and CTN-0051, X:BOT). Trial participants who were randomized to and initiated buprenorphine or methadone treatment and who identified as Hispanic, non-Hispanic Black, or non-Hispanic White were included in the present study. Data were analyzed from November 1, 2023, to August 5, 2024. THe main outcomes and measures were the maximum daily dose of buprenorphine or methadone received in each week for the first 4 weeks of treatment. The mean dose and percentage of patients receiving a higher dose (buprenorphine =16 mg and methadone =60 mg) were also compared across race and ethnicity groups.

A total of 1748 patients (1263 who initiated buprenorphine and 485 who initiated methadone treatment) were included in the analysis (1168 [66.8%] male; median age, 33 [IQR, 26-45] years). Of these, 138 patients (7.9%) identified as Black, 273 (15.6%) as Hispanic, and 1337 (76.5%) as White. In week 4, Black patients received buprenorphine doses 2.5 (95% CI -4.6 to -0.5) mg lower and methadone doses 16.7 (95% CI, -30.7 to -2.7) mg lower compared with White patients, after standardizing by age and sex. In week 4, the percentage of patients receiving a higher dose of medication (buprenorphine =16 mg; methadone =60 mg) was 16.9 (95% CI, -31.9 to -1.9) points lower for Black patients compared with White patients. Hispanic and White patients received similar buprenorphine doses; Hispanic patients received lower methadone doses than White patients.

Conclusions: In this cohort study of data from 3 clinical trials, White patients generally received higher doses of medication than Black patients. Future research is needed to understand the mechanisms of and interventions to reduce disparities in OUD treatment quality and how such disparities impact generalizability of trial results.

Note: An invited commentary piece on this article was also published by JAMA Network Open (Schiff DM, Nidey N, Tiako MJN. Dosing inequities in opioid use disorder treatment trials. JAMA Network Open 2024;7(10):e2436582.)

Related protocols: CTN-0027, CTN-0030, CTN-0051

There has been a significant increase in methamphetamine use and methamphetamine use disorder (Meth UD) in the United States, with evolving racial and ethnic differences. This secondary analysis of data from CTN-0069 (ADAPT-2) explored racial and ethnic differences in baseline sociodemographic and clinical characteristics as well as treatment effects on a measure of substance use recovery, depression symptoms, and methamphetamine craving among participants in a pharmacotherapy trial for Meth UD.

The ADAPT-2 trial (ClinicalTrials.gov number, NCT03078075; N=403; 69% male) was a multisite, 12-week randomized, double-blind, trial that employed a two-stage sequential parallel design to evaluate the efficacy of combination naltrexone (NTX) and oral bupropion (BUP) vs. placebo for Meth UD. Treatment effect was calculated as the weighted mean change in outcomes in the NTX-BUP minus placebo group across the two stages of treatment.

Of the 403 participants in the ADAPT-2 trial, the majority (65%) reported non-Hispanic White, while 14%, 11% and 10% reported Hispanic, non-Hispanic Black, and non-Hispanic other racial and ethnic categories respectively. At baseline non-Hispanic Black participants reported less severe indicators of methamphetamine use than non-Hispanic White. Treatment effects for recovery, depression symptoms and methamphetamine cravings did not significantly differ by race and ethnicity.

Conclusions: Although we found racial and ethnic differences at baseline, our findings did not show racial and ethnic differences in treatment effects of NTX-BUP on recovery, depression symptoms and methamphetamine cravings. However, our findings also highlight the need to expand representation of racial and ethnic minority groups in future trials.

Related protocols: CTN-0068

As overdose rates rise among non-White Americans, understanding barriers to substance use disorder (SUD) treatment access by race and ethnicity is important. This study explores self-reported barriers to SUD treatment by race and ethnicity in emergency department (ED) populations.

We conducted a secondary, exploratory analysis of a randomized trial of patients not seeking SUD treatment who endorsed active drug use at six academic EDs (CTN-0047). Responses to the Barriers to Treatment Inventory were compared by race, ethnicity, and drug severity, using 2 tests (N = 858), followed by adjusted logistic regression models.

Absence of a perceived drug problem (39% non-Hispanic Black, 38% Hispanic, 50% non-Hispanic White; p = .001) was the most prevalent barrier to SUD treatment. Non-Hispanic Black participants were less likely to state that they could handle their drug use on their own (OR = 0.69, CI = 0.50-0.95), and were more likely to report disliking personal questions than non-Hispanic White participants (OR = 1.49, CI = 1.07-2.09). Non-Hispanic Black participants were less likely than Hispanic participants to agree that treatment availability (OR = 0.46, CI = 0.28-0.76) and family disapproval (OR = 0.38, CI = 0.16-0.91) were treatment barriers.

Conclusions: Screening and counseling may help address the barrier, common to all groups, that drug use was not seen as problematic. Expanding access to diverse treatment options may also address the range of barriers reported by our study population. This study is one of the first in the U.S. to examine both individual and structural barriers to accessing treatment and to examine the association with drug use severity by race/ethnicity.

Related protocols: CTN-0047

American Indian and Alaska Native (AI/AN) populations are disproportionately affected by substance use disorders (SUDs) and related health disparities in contrast to other ethnoracial groups in the United States. Over the past 20 years, substantial resources have been allocated to NIDA’s National Drug Abuse Treatment Clinical Trials Network (CTN) to disseminate and implement effective SUD treatments in communities. However, we know little about how these resources have benefitted AI/AN peoples with SUD who arguably experience the greatest burden of SUDs. This review aims to determine lessons learned about AI/AN substance use and treatment outcomes in the CTN and the role of racism and Tribal identity.

The authors conducted a scoping review informed by the Joanna Briggs framework and PRISMA Extension for Scoping Reviews checklist and explanation. The study team conducted the search strategy within the CTN Dissemination Library and nine additional databases for articles published between 2000 and 2021. The review included studies if they reported results for AI/AN participants. Two reviewers determined study eligibility.

A systematic search yielded 13 empirical articles and six conceptual articles. Themes from the 13 empirical articles included: (1) Tribal Identity: Race, Culture, and Discrimination; (2) Treatment Engagement: Access and Retention; (3) Comorbid Conditions; (4) HIV/Risky Sexual Behaviors; and (5) Dissemination. The most salient theme was Tribal Identity: Race, Culture, and Discrimination, which was present in all articles that included a primary AI/AN sample (k = 8). Themes assessed but not identified for AI/AN peoples were Harm Reduction, Measurement Equivalence, Pharmacotherapy, and Substance Use Outcomes. The conceptual contributions used AI/AN CTN studies as exemplars of community-based and Tribal participatory research (CBPR/TPR).

Conclusions: CTN studies conducted with AI/AN communities demonstrate culturally congruent methods, including CBPR/TPR strategies; consideration/assessment of cultural identity, racism, and discrimination; and CBPR/TPR informed dissemination plans. Although important efforts are underway to increase AI/AN participation in the CTN, future research would benefit from strategies to increase participation of this population. Such strategies include reporting AI/AN subgroup data; addressing issues of cultural identity and experiences of racism; and adopting an overall effort for research aimed at understanding barriers to treatment access, engagement, utilization, retention, and outcomes for both treatment and research disparities for AI/AN populations.

Cocaine overdose death rates among Black people are higher than that of any other racial/ethnic group, attributable to synthetic opioids in the cocaine supply. Understanding the most effective psychostimulant use treatment interventions for Black people is a high priority. While some interventions have proven effective for the general population, their comparative effectiveness among Black people remains unknown. To address this gap, our NIDA-funded Clinical Trials Network (CTN) study 0125, will use Integrative Data Analysis (IDA) to examine treatment effectiveness across 9 CTN studies. This manuscript describes the study protocol for CTN-0125.

Of the 59 completed randomized clinical trials in the CTN with available datasets, nine met our inclusion criteria: 1) behavioral intervention, 2) targeted cocaine use or use disorder, 3) included sub-samples of participants who self-identified as Black and 4) included outcome measures of cocaine and psychostimulant use and consequences. We aim to 1) estimate scale scores of cocaine use severity while considering study-level measurement non-invariance, 2) compare the effectiveness of psychosocial treatments for psychostimulant use, and 3) explore individual (e.g., concomitant opioid use, age, sex, employment, pre-treatment psychiatric status) and study-level moderators (e.g., attendance/retention) to evaluate subgroup differences in treatment effectiveness.

Conclusions: The NIDA CTN provides a unique collection of studies that can offer insight into what interventions are most efficacious for Black people. Findings from our CTN-0125 have the potential to substantially inform treatment approaches specifically designed for Black people who use psychostimulants.

Related protocols: CTN-0125

As the U.S. grows more diverse, researchers decide how to include non-English speakers. Budget limitations may not allow for translation of all instruments. Study teams must determine which instruments must receive certified translations. This paper describes the procedures used in one U.S.-based, multi-site clinical trial to decide which study instruments should undergo certified translation and discusses dialect review procedures.

The team for NIDA Clinical Trials Network protocol CTN-0067 (the CHOICES-2 study) determined which instruments (n=31) would be translated using a qualitative evaluation to determine the need to obtain a Spanish-language certified translation: 1) “Could the meaning of these questions change (and potentially elicit a different response) if the translations were not consistent?” and 2) “Is it acceptable to have potential inconsistencies in these data?” Instruments for which question 1 was “yes” and question 2 was “no” (e.g., eligibility, outcomes, safety) were marked for certified translation. A dialect committee reviewed all translated patient-reported outcome measures to ensure that the translations had accounted for different meanings of words based on respondents’ countries or regions of origin and recommended changes where necessary.

Fourteen interview-based instruments underwent certified forward-only translation into U.S. Spanish. The remaining 2 interview-based instruments were translated via real-time conversation with participants by bilingual staff. Six forms were administrative and not translated. Five out of 9 professionally translated patient-reported outcome measures were amended to better reflect relevant dialects.

Conclusions: In the absence of specific guidance, it is feasible for study team members to 1) determine which instruments should undergo certified translation and 2) incorporate dialect into translations.

Related protocols: CTN-0067

This presentation from Leopoldo J. Cabassa, PhD, MSW (Center for Mental Health Services Research, Brown School of Social work, Washington University) presents strategies and ways to infuse equity approaches into implementation science studies to proactively address healthcare inequities in historically marginalized populations.

The extend to which clinical trials of medications for opioid use disorder (MOUD) are representative or not is unknown. Some patient characteristics modify MOUD effectiveness; if these same characteristics differ in distribution between the trial population and usual-care population, this could contribute to lack of generalizability — a discrepancy between trial and usual-care effectiveness. The objective of this study was to identify interpretable, multidimensional subgroups who were prescribed MOUD in substance use treatment programs in the US but who were not represented or under-represented by clinical trial participants.

This study was a secondary descriptive analysis of trial and real-world data. The trial data included 27 US opioid treatment programs in the NIDA National Drug Abuse Treatment Clinical Trials Network (CTN-0027, CTN-0051, and CTN-0030), N=2,199 patients. The real-world data included US substance use treatment programs that receive public funding, N=740,015 patients (TEDS-A data). The authors characterized real-world patient populations who were non-represented and under-represented in the trial data in terms of sociodemographic and clinical characteristics that could modify MOUD effectiveness.

The authors found that 10.7% of MOUD patients in TEDS-A (real-world sample) were not represented in the three clinical trials. As expected, pregnant MOUD patients (n=19,490) were not represented. Excluding pregnancy, education, and marital status from the characteristics, 2.6% of MOUD patients were not represented. Patients aged 65 years and older (n=11,204) and those 50-64 years who identified as other (non-white, non-Black, and non-Hispanic) race/ethnicity or multi-racial (n=7,281) were under-represented.

Conclusions: Quantifying and characterizing non- or under-represented subgroups in trials can provide the data necessary to improve representation in future trials and address research-to-practice gaps.

Related protocols: CTN-0027, CTN-0030, CTN-0051

This CTN platform study aimed to examine characteristics associated with disparities in digital access (i.e., access to high speed Internet via a computer or smartphone) in American rural and urban households given that digital access has a direct impact on access to telemedicine-based services.

Using the 2019 American Community Survey, researchers from the Greater Southern California Node analyzed the proportions of geographic area, race/ethnicity, and socioeconomic status according to device and high-speed Internet access. Maximum likelihood logit estimators estimated how these factors influenced device and high-speed Internet access. Of 105,312,959 households, 32.29% were without a desktop or laptop computer with high-speed Internet (WDW), 21.51% were without a smartphone with a data plan for wireless Internet (WSW), and 14.02% were without any digital access (WDA). Nonmetropolitan households were significantly more likely to be WDA than metropolitan households. Relative to non-Hispanic Whites, non-Hispanic Blacks, American Indian or Alaska Natives, or Hispanics were significantly more likely to be WDA. When compared to households with private health insurance coverage, households WDA were significantly more likely to have no insurance or public insurance coverage. Households with any digital access reported higher income and more family members living at home. Using the same predictors, similar findings were reported for households WDW or WSW.

Conclusions: Significant disparities in digital access exist among nonmetropolitan households, racial/ethnic minority households, and lower-income households. The lack of digital access has implications for the accessibility of health care services via telemedicine and thus could exacerbate health disparities.

Opioid use and opioid-related overdose continue to rise among racial/ethnic minorities. Social determinants of health negatively impact these communities, possibly resulting in poorer treatment outcomes. Research is needed to investigate how to overcome the disproportionate and deleterious impact of social determinants of health on treatment entry, retention, drug use and related outcomes among racial/ethnic minorities. The current commentary provides recommendations that may help researchers respond more effectively to reducing health disparities in substance use treatment.

In this commentary piece, the authors begin with recommendations of best research practices (e.g., ensuring adequate recruitment of racial/ethnic minorities in research, central components of valid analysis, and adequate methods for assessing effect sizes for racial/ethnic minorities). Then, they propose that more NIDA research focus on issues disproportionately affecting racial/ethnic minorities. Next, techniques for increasing the number of underrepresented racial/ethnic treatment researchers are suggested. The authors then recommend methods for infusing racial/ethnic expertise onto funding decision panels. The commentary ends with a case study that features NIDA’s National Drug Abuse Treatment Clinical Trials Network (CTN).

Conclusions: The proposed recommendations can serve as guidelines for substance use research funders to promote research that has the potential to reduce racial/ethnic disparities in substance use treatment and to increase training opportunities for racial/ethnic minority researchers.

There are a wide variety of methods for using combustible cannabis which may impact an individual’s pattern of use as well as their response to cannabis use disorder (CUD) treatment. Previous research has noted racial/ethnic differences in cannabis users’ preferred method of use.

This study examined data from a randomized placebo-controlled trial of a pharmacological intervention for adults with CUD (CTN-0053). Latent profile analysis classified participants (N=302) based on their primary method of combustible cannabis use.

A four profile solution emerged that identified participants who demonstrated 1) Primarily Joint (n=50), 2) Primary Blunt (n=106), 3) Mixed Method of Use (MoU; n=30), and 4) Primarily Pipe (i.e. pipe or bong; n=116) use. Profiles were compared on socio-demographic characteristics and racial differences were found among the four latent profiles as well as differences in their level of use. Cannabis users with a preference for joints were more likely to be White as compared to other racial groups. In contrast, a greater proportion of participants with a preference for blunts were African American. The Primarily Joint profile was found to have the highest cannabis relapse rate at 1-month follow-up (94%) which was significantly greater than the Mixed MoU (74%) and Primarily Pipe (78%) profiles. Interestingly, there was no difference in 1-month follow-up cannabis relapse rates between the Primarily Joint and Primarily Blunt profiles (87%).

Conclusions: Findings suggest that treatment-seeking individuals who primarily use joints or blunts may face unique challenges that may impact cannabis abstinence. Along with other cannabis-related characteristics, an individual’s preferred method of use may represent an important factor to consider in the treatment of CUD.

Related protocols: CTN-0053

Research studies suggest racial/ethnic differences in posttraumatic stress disorder (PTSD) diagnosis and symptom severity. Few studies to date, however, have examined the extent to which these findings are due to differences in measurement properties of existing PTSD scales. This study examined measurement equivalence across race/ethnicity in the Clinician-Administered PTSD Scale (CAPS) by testing for differential item functioning (DIF) in the item response theory (IRT) framework.

Participants were 506 trauma-exposed women (M=39.41 years), who participated in the NIDA Clinical Trials Network Women and Trauma study (CTN-0015). PTSD severity score estimates were improved upon as part of IRT estimation incorporating symptom “weights” (i.e., factor loadings) and group-specific DIF. Six symptoms from the CAPS showed DIF, with the majority of differences in measurement driven by White/African Americans and White/Latina differences, particularly for (a) avoidance of thoughts and (b) a sense of foreshortened future. Despite both racial/ethnic minority groups being slight (not significantly) more likely to receive a PTSD diagnosis, African Americans and Latinas had significantly lower PTSD severity scores than Whites as estimated under IRT with group-specific DIF. Examination of PTSD severity scores based on symptom counts revealed these differences were either dampened or entirely negated.

Conclusions: These findings suggest the importance of considering differences in symptom relevance across race/ethnicity and their impact on capturing symptom severity parallel to diagnostic criteria. Implications for clinical practice are discussed.

Related protocols: CTN-0015