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Abstract: High levels of missing outcome data for biologically confirmed substance use (BCSU) threaten the validity of substance use disorder (SUD) clinical trials. Underlying attributes of clinical trials could explain BCSU missingness and identify targets for improved trial design. We reviewed 21 clinical trials funded by the NIDA National Drug Abuse Treatment Clinical Trials Network (CTN) and published from 2005 to 2018 that examined pharmacologic and psychosocial interventions for SUD. We used configurational analysis-a Boolean algebra approach that identifies an attribute or combination of attributes predictive of an outcome-to identify trial design features and participant characteristics associated with high levels of BCSU missingness. Associations were identified by configuration complexity, consistency, coverage, and robustness. We limited results using a consistency threshold of 0.75 and summarized model fit using the product of consistency and coverage. For trial design features, the final solution consisted of two pathways: psychosocial treatment as a trial intervention OR larger trial arm size (complexity=2, consistency=0.79, coverage=0.93, robustness score=0.71). For participant characteristics, the final solution consisted of two pathways: interventions targeting individuals with poly- or nonspecific substance use OR younger age (complexity=2, consistency=0.75, coverage=0.86, robustness score=1.00). Conclusions: Psychosocial treatments, larger trial arm size, interventions targeting individuals with poly- or nonspecific substance use, and younger age among trial participants were predictive of missing BCSU data in SUD clinical trials. Interventions to mitigate missing data that focus on these attributes may reduce threats to validity and improve utility of SUD clinical trials. Related protocols: CTN-0002, CTN-0003, CTN-0004, CTN-0006, CTN-0007, CTN-0009. CTN-0013, CTN-0014, CTN-0015, CTN-0017, CTN-0021, CTN-0029, CTN-0030, CTN-0031, CTN-0037, CTN-0044, CTN-0046, CTN-0048, CTN-0051, CTN-0053

Abstract:

Symptom counts as the basis for Post-Traumatic Stress Disorder (PTSD) diagnoses in the DSM presume each symptom is equally reflective of underlying disorder severity. However, the “equal weight” assumption fails to fit PTSD symptom data when tested. The present study, funded in part by CTN-0015, developed an enhanced PTSD diagnosis based on (a) a conventional PTSD diagnosis from a clinical interview and (b) an empirical classification of full PTSD that reflected the relative clinical weights of each symptom.

Baseline structured interview data from Project Harmony (N = 2658) was used. An enhanced diagnosis for full PTSD was estimated using an empirical threshold from moderated nonlinear factor analysis (MNLFA) latent PTSD scale scores, in combination with a full conventional PTSD diagnosis based on interview data.

One in 4 patients in the sample had a PTSD diagnosis that was inconsistent with their empirical PTSD grouping, such that the enhanced diagnostic standard reduced the diagnostic discrepancy rate by 20%. Veterans, and in particular female Veterans, were at greatest odds for discrepancy between their underlying PTSD severity and DSM diagnosis.

Conclusions: Psychometric methodologies that differentially weight symptoms can complement DSM criteria and may serve as a platform for symptom prioritization for diagnoses in future editions of DSM.

Related protocols: CTN-0015

Abstract:

Black women are at heightened risk for trauma exposure, post-traumatic stress disorder (PTSD), and substance use disorders (SUDs) compared to white women and the general population. However, disparities in treatment engagement and retention persist, particularly for Black women with co-occurring PTSD and SUD. Although therapeutic alliance is an important predictor and mediator of treatment retention and outcomes, we know little about predictors of alliance and the mediating role of alliance for PTSD+SUD outcomes among Black women.

This study used data previously collected for the National Drug Abuse Treatment Clinical Trials Network (CTN) Women and Trauma Study (CTN-0015), which compared Seeking Safety (a cognitive-behavioral intervention for PTSD+SUD) to Women’s Health Education (control). It includes 88 Black/African American women from both arms of the original trial. Measures included the Helping Alliance Questionnaire, Addiction Severity Index-Lite, and Clinician Administered PTSD Scale. Women in the intervention arm also completed the Seeking Safety Feedback Questionnaire.

Stepwise, hierarchical linear regressions indicted that years of education and previous alcohol/drug treatment attempts significantly predicted early alliance in the second week of therapy, but not late alliance in the last week of therapy. Greater education and more treatment attempts were associated with higher early alliance. Alliance did not mediate relationships between these significant predictors and treatment outcomes (e.g., attendance, post-treatment PTSD and SUD symptoms) or treatment feedback in the Seeking Safety group.

Conclusions: Education and prior treatment attempts predicted early alliance among Black/African American women in PTSD+SUD group treatment, and higher education level was associated with poorer Seeking Safety feedback topic ratings. Educational level and treatment history should be considered during alliance building in therapeutic interventions with Black women. Clinicians may consider the integration of pre-treatment alliance-building strategies with Black female patients who have lower levels of education. This study provides insight into the relative impact of several important factors that influence early alliance among Black women with co-occurring PTSD and SUD.

Related protocols: CTN-0015

Abstract:

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

Abstract:

Most of the work on understanding subthreshold PTSD has focused on inconsistencies in defining subthreshold PTSD and how those inconsistencies impact prevalence rates. The present study distinguishes between full and subthreshold PTSD using empirical categorization and assesses the circumstances under which empirical categorization is discordant with full and subthreshold PTSD diagnoses.

Using data from the NIDA Clinical Trials Network protocol “Women’s Treatment for Trauma and Substance Use Disorders” (CTN-0015), researched used a modernized adaptation of the Jacobson and Truax (1991) framework, assessing whether patients were above or below an empirical threshold on latent PTSD severity scores estimated under categorical confirmatory factor analysis; the empirical categorizations were then crossed with the diagnosis to form four diagnostic by empirical categorization groupings.

Compared to a reference group (full PTSD diagnosis and empirical categorization), patients who had a full PTSD diagnosis but a subthreshold empirical categorization had lower symptom endorsement rates on 15 PTSD symptoms, were more likely to be married, ethnic minorities with fewer lifetime traumas. Conversely, patients with a subthreshold PTSD diagnosis and a full PTSD empirical grouping looked similar to “Full/Fulls,” only differing on avoidance symptoms.

Conclusions: Although alternative definitions of subthreshold PTSD and coding of symptom endorsement, as well as use of DSM-IV symptoms (though reconciled against overlapping symptoms from DSM-5), may impact results, these results suggest that empirical categorization can be a useful supplement to diagnosis in distinguishing subthreshold PTSD from full PTSD, using a methodology that could provide a platform for melding dimensional and categorical nosology approaches in the DSM.

Related protocols: CTN-0015

Abstract:

The “Women and Trauma” Study (WTS) conducted in the National Drug Abuse Treatment Clinical Trials Network (CTN-0015) resulted in research publications, presentations, and a train-the-trainer workshop to support dissemination efforts for skills-based trauma treatment in substance use community treatment. Twelve years after its completion, this paper aims to examine whether and how the WTS contributed to knowledge in the field of trauma and addictions and inspired community treatment programs (CTPs) to train staff to identify and provide trauma-related services.

This article presents findings from two different analyses that explored longer-term study impacts on treatment and dissemination: (1) a post-study site survey covering 4 domains from 4/7 programs that participated in delivering the WTS to evaluate their perceptions of study impact on their treatment community; and (2) an analysis of citations of its publications to determine impact on the scientific community.

Surveys from responding sites indicated that participation in the study significantly increased their agencies” awareness of the need to take a focused approach to treating trauma issues in this population. Specifically, these sites increased their commitment to using skills-based trauma treatment with the study’s target population of female patients with SUD and trauma histories, as well as expanding it to other groups affected by trauma. Citation analysis revealed that according to the Web of Science, as of August 2019, the number of citations of 24 CTN-0015 articles, ranged from 1 to 135 (Mean = 20, SD = 33; Median = 6). Four of the most influential are discussed.

Conclusions: This article provides original information about the contributions of the WTS study, demonstrating how the study contributed to serving women with trauma in community substance use treatment.

Related protocols: CTN-0015

Abstract:

The extent to which behavioral drug abuse treatments affect sexual risk behaviors is largely unknown. This study examined the impact of behavioral drug abuse treatments on sexual risk behaviors using an integrative data analysis approach across eight trials conducted within the NIDA Clinical Trials Network (CTN-0004, 0005, 0006, 0007, 0009, 0013, 0015, and 0021). Participants (N=1305) from eight randomized controlled trials who were sexually active at baseline were included in the pooled dataset; 48.7% were female, 64.1% self-identified as a racial/ethnic minority, with M (SD) age of 34.9 (9.6). Longitudinal logistic regression estimated the probability of risky sexual behavior (i.e., inconsistent condom use and/or > 1 sexual partner in past 30 days) post-intervention with an indicator variable (1 for post-intervention), study condition (control, intervention), and their interaction as predictors; the analysis employed random effects for each trial and included relevant control variables. Time-varying differences in effects based on weeks post-intervention were incorporated using interacted linear and quadratic terms with condition status. Approximately 84.2% reported risky sexual behaviors at baseline. The control and intervention conditions were 18.5 and 17.3 percentage points less likely to report risky sexual behavior post-intervention, respectively.

Conclusions: Results suggest decreasing rates of risky sex engagement until 8 weeks (control) or 9 weeks (intervention post-intervention; risky sexual behavior subsequently increased. Behavioral CTN trial participation was associated with decreased sexual risk behaviors in both the intervention and control trial conditions. Given the heterogeneity of treatment approaches employed across the 8 CTN trials, these results point to the effectiveness of behavioral drug abuse treatment to reduce sexual risk behaviors. To bolster further reductions in sexual risk behavior engagement, there is a need to identify HIV risk reduction interventions that can best be integrated within existing resource-limited substance use disorder treatment programs.

Related protocols: CTN-0004, CTN-0005, CTN-0006, CTN-0007, CTN-0009, CTN-0013, CTN-0015, CTN-0021

Abstract:

While the detrimental effects of concurrent substance use disorders (SUDs) are now being well documented, very few studies have examined this comorbidity among women with posttraumatic stress disorder (PTSD). Data for these analyses were derived from the “Women and Trauma” study conducted within the NIDA Clinical Trials Network. Women with full or subthreshold PTSD and co-occurring cannabis use disorder (CUD) and cocaine use disorder (COD; N=99) were compared to their counterparts with co-occurring CUD only (N=26) and co-occurring COD only (N=161) on rates of trauma exposure, psychiatric disorders, psychosocial problems, and other substance use utilizing a set of multivariate logistic regressions. In models adjusted for age and race/ethnicity, women with PTSD and COD only were significantly older than their counterparts with CUD only and concurrent CUD+COD. Relative to those with CUD only, women with concurrent CUD+COD had higher odds of adult sexual assault. Relative to those with COD only, women with concurrent CUD+COD had higher odds of alcohol use disorder in the past 12 months. Finally, relative to those with CUD only, women with COD only had higher odds of ever being arrested/convicted and adult sexual assault.

Conclusions: The higher rates of adult sexual assault and alcohol use disorder among those with concurrent CUD+COD suggest the need for trauma-informed approaches that can response to the needs of this dually-diagnosed population. Moreover, the causal link between repeated traumatic stress exposure and polysubstance use requires further examination.

Related protocols: CTN-0015

Abstract:

Eating disorders (ED) and substance use disorders (SUD) commonly co-occur, especially in conjunction with posttraumatic stress disorder (PTSD), yet little is known about ED and ED symptoms in women presenting to addiction treatment programs. This study examined the association between ED symptoms and substance use frequency and severity in a sample of women with a DSM IV diagnosis of current SUD and PTSD enrolled in SUD treatment. Participants were 122 women from four substance abuse treatment sites who participated in a multi-site clinical trial through NIDA’s Clinical Trials Network (CTN). The Eating Disorder Examination-Questionnaire (EDE-Q), the Clinician Administered PTSD Scale (CAPS), and the Addiction Severity Index (ASI) were administered at baseline and correlational analyses were performed. Variables that significantly correlated with EDE-Q total and subscale scores were entered into a linear regression analysis. Results found that scores on the EDE-Q Global scale, as well as the Eating Concern, Weight Concern, and Shape Concern subscales of the EDE-Q were significantly associated with Caucasian race/ethnicity, past 30 day opiate use, higher ASI Psychiatric Subscale score, and lower ASI Employment Subscale score.

Conclusions: Women in recovery from SUD and PTSD reported concerns about weight, shape, and eating at a higher rate than in the general US population of women. The finding that past 30 day opiate use was associated with EDE scores may indicate that opiates also play a substantial role in disordered eating symptoms. Though exploratory, these findings suggest that there may be a relationship between addiction severity, use of certain drugs of abuse, and eating disorder symptoms, particularly those involving weight and shape concerns in women with comorbid PTSD and SUD. Comprehensive and integrated treatment approaches need to be developed to address this complex but common comorbidity.

Related protocols: CTN-0015, CTN-0015-A-1

Abstract:

Recent federal legislation and a renewed focus on integrative care models underscore the need for economical, effective, and science-based behavioral health care treatment. As such, maximizing the impact and reach of treatment research is of great concern. Behavioral health issues, including the frequent co-occurrence of substance use disorders (SUD) and post-traumatic stress disorder (PTSD), are often complex, with a myriad of factors contributing to the success of interventions. Although treatment guides for comorbid SUD/PTSD exist, most patients continue to suffer symptoms following the prescribed treatment course. Further, the study of efficacious treatments has been hampered by methodological challenges (e.g., overreliance on “superiority” designs (i.e., designs structured to test whether or not one treatment statistically surpasses another in terms of effect sizes) and short term interventions). Secondary analyses of randomized controlled clinical trials offer potential benefits to enhance understanding of findings and increase the personalization of treatment.

This paper offers a description of the limits of randomized controlled trials as related to SUD/PTSD populations, highlights the benefits and potential pitfalls of secondary analytic techniques, and uses as a case example one of the largest effectiveness trials of behavioral treatment for co-occurring SUD/PTSD conducted within the National Drug Abuse Treatment Clinical Trials Network (CTN). The paper concludes with implications of this secondary analytic approach to improve addiction researchers’ ability to identify best practices for community-based treatment of these disorders.

Conclusions: Innovative methods are needed to maximize the benefits of clinical studies and better support SUD/PTSD treatment options for both specialty and non-specialty healthcare settings. Given the continuing gap between research and practice, appropriately executed secondary analytic studies are an important step in addressing questions that have real-world value to community clinicians. Moving forward, planning for and description of secondary analyses in randomized trials should be given equal consideration and care to the primary outcome analysis.

Abstract:

Despite advances toward integration of care for women with co-occurring substance use disorder (SUD) and post-traumatic stress disorder (PTSD), low abstinence rates following SUD/PTSD treatment remain the norm. The utility of investigating distinct substance use trajectories is a critical innovation in the detection and refining of effective interventions for this clinical population. The present study reanalyzed data from the largest randomized clinical trial to date for co-occurring SUD and PTSD in women (National Drug Abuse Treatment Clinical Trials Network protocol CTN-0015, “Women’s Treatment for Trauma and Substance Use Disorders”). Randomized participants (n=353) received one of two interventions in addition to treatment as usual for SUD: 1) trauma-informed integrative treatment for PTSD/SUD (Seeking Safety); or 2) an active control psychoeducation course on women’s health (Women’s Health Education).

The present study utilized latent growth mixture models (LGMM) with multiple groups to estimate women’s substance use patterns during the 12-month follow-up period. Findings provided support for three different trajectories of substance use in the post-treatment year: 1) consistently low likelihood and use frequency; 2) consistently high likelihood and use frequency; and 3) high likelihood and moderate use frequency. Covariate analyses revealed improvement in PTSD severity was associated with membership in a specific substance use trajectory, although receiving trauma-informed treatment was not. Additionally, SUD severity, age, and after-care efforts were shown to be related to trajectory membership.

Conclusions: Findings highlight the necessity of accounting for heterogeneity in post-treatment substance use, relevance of trauma-informed care in SUD recovery, and benefits of incorporating methodologies like LGMM when evaluating SUD treatment outcomes. For women dually diagnosed with PTSD and SUD, the current study established the presence of several varied clinical presentations linked to substance use following treatment, each with potentially different needs, vulnerabilities, and strengths. Results of this study also point to opportunities for tailing interventions to the specific clinical presentation and potential impact of these choices on a woman’s trajectory of recovery.

Abstract:

This secondary analysis of data from National Drug Abuse Institute Clinical Trials Network protocol CTN-0015, “Women’s Treatment for Trauma and Substance Use Disorders,” investigated the impact of 12 sessions of Seeking Safety (SS) on reducing posttraumatic stress disorder (PTSD) symptoms in a sample of dually diagnosed women with physical disabilities versus nondisabled (ND) women. SS is an evidence-based and widely implemented manualized therapy for PTSD and/or substance use disorder. It is a present-focused model that promotes coping skills and psychoeducation. In CTN-0015, 353 participants with current PTSD and substance use disorder (SUD) were randomly assigned to partial-dose SS or Women’s Health Education (WHE) group therapy conducted in a community-based substance abuse treatment program. The women were categorized as participants with disabilities (PWD; n=20) or ND (n=333) based on the question, “Do you receive a pension for a physical disability?” PTSD was assessed with the Clinician-Administered PTSD Scale (CAPS) at baseline and follow-ups after treatment (1 week, 3 months, 6 months, and 12 months). PWD experienced sustained reductions in PTSD symptoms when treated with SS but not WHE. Indeed, PTSD symptoms of PWD in WHE returned to baseline levels of severity by 12-month follow-up. This pattern of results was not observed among ND women, who sustained improvements on PTSD in both treatment conditions.

Conclusions: These results suggest strong potential for using Seeking Safety to treat PTSD among women with physical disabilities, an intervention that may be particularly relevant for this population by providing a trauma focus without requiring clients to delve into painful traumatic memories and instead offering a present and optimistic focus on coping skills and education. This is a vulnerable population for whom trauma is bound up closely with disability; the finding here, that women with disabilities had better outcomes in the Seeking Safety group than the Women’s Health Education group, speaks to the genuine need to address trauma and PTSD more directly in those with disabilities.

Related protocols: CTN-0015

Abstract:

Given high drop-out rates and difficulties with retention among women in treatment for co-occurring post-traumatic stress disorder (PTSD) and substance use disorders (SUD), research to determine the specific conditions under which this population can best be engaged and benefit from treatment is important. This study examined the relationship between racial/ethnic match and treatment outcomes for 224 women who participated in a National Drug Abuse Treatment Clinical Trials Network (CTN) study of group treatments for posttraumatic stress disorder (PTSD) and substance use disorders, “Women’s Treatment for Trauma and Substance Use Disorders” (CTN-0015). 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.

Conclusions: Overall, these findings revealed the complexity of racial/ethnic matching between client and therapist and its impact, particularly within a group treatment context. While racial/ethnic matching may provide, in some circumstances, a context that facilitates understanding, enhances trust, and strengthens the alliance; under other conditions, racial/ethnic matching may not confer additional benefits. These findings highlight the need for further examinations into individual and subgroup differences in the benefits of racial/ethnic matching.

Related protocols: CTN-0015

Abstract:

Sleep disruption appears not only to reflect a symptom of posttraumatic stress disorder (PTSD), but also a unique vulnerability for its development and maintenance. Studies examining the impact of psychosocial treatments for PTSD on sleep symptoms are few and no studies to date have examined this question in samples with co-occurring substance use disorders. This study is a secondary analysis of a large clinical trial comparing two psychological treatments for co-occurring PTSD and substance use disorders (National Drug Abuse Treatment Clinical Trials Network protocol CTN-0015, “Women’s Treatment for Trauma and Substance Use Disorders”). Women (n=353) completed measures of PTSD at baseline, end of treatment, and 3-, 6-, and 12-month follow-ups. Results indicated that the prevalence of insomnia, but not nightmares, decreased during treatment, and that 63.8% of participants reported at least 1 clinical-level sleep symptom at the end of treatment. Improvement in sleep symptoms during treatment was associated with better overall PTSD outcomes over time.

Conclusions: These results extend the existing literature to suggest that residual sleep disruption following PTSD treatment is common in women with co-occurring PTSD and substance use disorders. Although based on the design of the study, no causal conclusions can be drawn, the findings imply that among those with clinical-level residual sleep disruption, risk for continuation or exacerbation of overall PTSD symptoms may be higher. Consideration of the addition of interventions targeted to sleep disruption may be indicated in those with PTSD and SUD, or considered as an adjunctive intervention if residual sleep disruption is present at the time of treatment completion.

Related protocols: CTN-0015

Abstract:

This study examined in- and post-treatment mediation effects of a 12-session dose of Seeking Safety (SS) — an integrative cognitive behavioral treatment for comorbid PTSD and SUDs — on alcohol and cocaine outcomes in comparison to Women’s Health Education (WHE) in a seven-site randomized controlled effectiveness trial, CTN protocol 0015, “Women’s Treatment for Trauma and Substance Abuse.” Women (n=353) enrolled in outpatient substance abuse treatment, who had experienced multiple traumas in childhood and/or adulthood and who had comorbid PTSD, were randomly assigned to receive SS or WHE delivered in open enrollment groups for 12 sessions in 6 weeks (unlike the full 25-topic SS protocol). Data were analyzed under two forms of longitudinal mediation analysis, each accounting for changes over time in group membership and group context, respectively. Women in SS, compared to WHE, showed significantly steeper decreases in PTSD frequency and severity, which in turn showed significant impact in reducing both cocaine and alcohol use. This pattern was strongest for those who completed most of the treatment sessions, which was the majority of patients in the trial; these patterns only emerged during the in-treatment phase.

Conclusions: Use of an integrated approach to PTSD/SUD such as Seeking Safety can be helpful in more rapidly reducing PTSD, which consequently reduces SUD symptoms, particularly for those who attend most of the available treatment sessions. This is one of the first studies to illustrate such effects in treating comorbid PTSD and SUD in the context of a highly impaired population delivered by community-based providers.

Related protocols: CTN-0015