Search the Library

Abstract: This study aimed to estimate health state utility values (HSUVs) for the key health states found in opioid use disorder (OUD) cost-effectiveness models in the published literature. Data were obtained from six trials representing 1,777 individuals with OUD in the NIDA Clinical Trials Network (CTN-0001, -0002, -0009. -0030, -0049, and -0051). Researchers implemented mapping algorithms to harmonize data from different measures of quality of life (the SF-12 Versions 1 and 2 and the EQ-5D-3 L). They performed a regression analysis to quantify the relationship between HSUVs and the following variables: days of extra-medical opioid use in the past 30 days, injecting behaviors, treatment with medications for OUD, HIV status, and age. A secondary analysis explored the impact of opioid withdrawal symptoms. There were statistically significant reductions in HSUVs associated with extra-medical opioid use (-0.002 (95% CI [-0.003,-0.0001]) to -0.003 (95% CI [-0.005,-0.002]) per additional day of heroin or other opiate use, respectively), drug injecting compared to not injecting (-0.043 (95% CI [-0.079,-0.006])), HIV-positive diagnosis compared to no diagnosis (-0.074 (95% CI [-0.143,-0.005])), and age (-0.001 per year (95% CI [-0.003,-0.0002])). Parameters associated with medications for OUD treatment were not statistically significant after controlling for extra-medical opioid use (0.0131 (95% CI [-0.0479,0.0769])), in line with prior studies. The secondary analysis revealed that withdrawal symptoms are a fundamental driver of HSUVs, with predictions of 0.817 (95% CI [0.768, 0.858]), 0.705 (95% CI [0.607, 0.786]), and 0.367 (95% CI [0.180, 0.575]) for moderate, severe, and worst level of symptoms, respectively. Conclusions: Researchers for this study observed HSUVs for OUD that were higher than those from previous studies that had been conducted without input from people living with the condition. Related protocols: CTN-0001, CTN-0002, CTN-0009, CTN-0030, CTN-0049, CTN-0051

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:

The purpose of this study was to estimate obesity prevalence among drug-dependent individuals and to compare prevalence across different types of drug dependence.

1596 opioid- and/or stimulant-dependent participants were extracted from six clinical trials within the National Drug Abuse Treatment Clinical Trials Network of the National Institute on Drug Abuse (NIDA CTN) to estimate obesity prevalence among drug-dependent users. Age-, sex-, and race-matched National Health and Nutrition Examination Survey (NHANES) samples were used as a general population reference. Standardized prevalence ratios (SPRs) were calculated to compare the CTN sample to NHANES as well as to compare within the CTN sample. Logistic regression estimated associations between the type of drug dependence and obesity.

The standardized obesity prevalence among the drug-dependent CTN trial participants was 67% of expected for age-, sex- and race-matched NIHANES participants (SPR = 0.67, 95% CI: 0.60-0.74). Obesity was least prevalent among opioid-dependent-only participants (SPR = 0.36, 95% CI: 0.27-0.46 compared to the NHANES, and SPR = 0.33, 95% CI: 0.23-0.46 compared to the stimulant-dependent-only participants). Compared to stimulant-dependent-only users (p < 0.0001), the odds of obesity were 67% lower among opioid-dependent-only users (adjusted odds ratio [AOR] = 0.33, 95% CI: 0.23-0.46) and 33% lower among opioid and stimulant-co-dependent users (AOR = 0.67, 95%CI: 0.49-0.90) after controlling for age, sex, race, education and employment pattern.

Conclusions: The prevalence of obesity among drug-dependent clinical trial participants was lower than the general population, and lowest among opioid-dependent-only users, suggesting an inverse relationship between obesity prevalence and drug dependence, most notable among opioid-dependent-only users.

Related protocols: CTN-0001, CTN-0002, CTN-0003, CTN-0037, CTN-0046, CTN-0048

Abstract:

HIV infection disproportionately impacts minorities, yet research on racial/ethnic differences in the prevalence and correlates of HIV risk behaviors is limited. This study examined racial/ethnic differences in the rates of HIV risk behaviors and whether the relationship between HIV risk factors and HIV risk behaviors varies by race/ethnicity in clients participating in National Drug Abuse Treatment Clinical Trial Network (CTN) trials. The sample was 41% non-Hispanic White, 32% non-Hispanic Black, and 27% Hispanic (N = 2,063). HIV risk behaviors and measures of substance and psychosocial HIV risk factors in the past month were obtained. Non-Hispanic Blacks engaged in less HIV sexual risk behaviors overall than non-Hispanic Whites. While non-Hispanic Whites were the most likely to report any injection drug use, Hispanics engaged in the most HIV drug risk behaviors. Specific risk factors were differentially predictive of HIV risk behavior by race/ethnicity. Alcohol use severity was related to engaging in higher sex risk behaviors for non-Hispanic Blacks and Whites. Greater psychiatric severity was related to engaging in higher sex risk behaviors for non-Hispanic Whites. Drug use severity was associated with engaging in higher risk drug behaviors for non-Hispanic Whites and Hispanics, with the magnitude of the relationship stronger for Hispanics.

Conclusions: The findings from the present study suggest that there is a context in which HIV high risk behaviors occur within racial/ethnic groups as well as differences in the presence of risk factors associated with engaging in those behaviors. These findings are consistent with calls to culturally adapt evidence-based interventions and the need to maintain core elements of the intervention when adapting the intervention for increased relevance to the new targets. Further research testing HIV risk prevention interventions within racial/ethnic groups is needed to identify target behaviors or risk factors that are salient to inform HIV interventions.

Related protocols: CTN-0001, CTN-0002, CTN-0004, CTN-0005, CTN-0006, CTN-0007, CTN-0021

Abstract:

This presentation examines the variety of barriers that get in the way of implementation of medication-assisted treatments for substance abuse. Barriers can be encountered at every level of treatment, from the client level, to the clinician, organizational, and environmental (regulatory, e.g.) levels. Attitudes of both clinicians and patients when it comes to taking medications to treat substance abuse are a common barrier, with many believing drug addiction should not be treated with a drug, or that abstinence is the only approach. MAT itself can be a barrier, if medications are unavailable, dosage is insufficient, or patients fail to comply.

The presentation ends with a discussion of methods for reducing barriers to MAT, including offering medications at reduced cost, increasing access to medical personnel in your area, and education/training (such as the NIDA/SAMHSA Blending Team Products on buprenorphine or Addiction Technology Transfer Center (ATTC) trainings). Participation in medication trials, such as the Ohio Valley Node’s involvement in the National Drug Abuse Treatment Clinical Trials Network’s buprenorphine studies (CTN-0001 and CTN-0002) can help introduce clinicians and treatment centers to evidence-based practices for MAT, and decrease some of the barriers to implementation in their organizations.

Related protocols: CTN-0001, CTN-0002

Abstract:

This article reports on an ancillary investigation of data from protocols CTN-0001 and CTN-0002 (Buprenorphine/Naloxone versus Clonidine for Inpatient/Outpatient Opiate Detoxification). The sample included 343 opioid-dependent adults enrolled in the protocols. Researchers examined associations between depressive symptoms, co-occurring substance use (i.e., the use of substances other than opioids), and HIV-related sexual and injection risk behaviors. Data were collected using the Addiction Severity Index and the HIV Risk Behavior Scale, and analyzed using linear regression. Depressive symptoms were associated with an increased level of injection risk behaviors but were not associated with risky sexual behaviors. The co-occurring use of amphetamines also increased the likelihood of risky sexual behaviors.

Conclusions: Treatment of depression can make a contribution to decreasing injection risk among opioid-dependent injection drug users, especially if combined with other risk reduction interventions. This study also revealed that noninjecting amphetamine use was independently associated with sexual risk behaviors among opioid-dependent individuals.

Supported by the Duke Clinical Research Institute (CTN DSC 1).

Related protocols: CTN-0001, CTN-0002

Abstract:

Selection of appropriate outcome measures is important for clinical studies of drug addiction treatment. Researchers use various methods for collecting drug use outcomes and must consider substances to be included in a urine drug screen (UDS), accuracy of self-report, use of various instruments and procedures for collecting self-reported drug use, and timing of outcome assessments. This study sought to define a set of candidate measures to (1) assess their intercorrelation and (2) identify any differences in results. To that end, data were combined from seven completed protocols in the National Drug Abuse Treatment Clinical Trials Network (CTN), with a total of 1897 participants. Nine outcome measures were defined, based on UDS, self-report, or a combination, then multivariable, multilevel generalized estimating equation models were used to assess subgroup differences in intervention success, controlling for baseline differences and accounting for clustering by CTN protocols. Results found high correlations among all candidate outcomes. All outcomes showed consistent overall results with no significant intervention impact on drug use during follow-up. However, with most UDS variables, but not with self-report or “corrected self-report,” a significant gender–ethnicity interaction with benefit shown in African American women, White women, and Hispanic men was observed.

Conclusions: Despite strong associations between candidate measures, important differences in results were found. This study demonstrates the potential utility and impact of combining UDS and self-report data for drug use assessment. The results suggest possible differences in intervention efficacy by gender and ethnicity, but highlight the need to cautiously interpret observed interactions. Additional studies like this one will help guide implementation of methodological recommendations to construct combined measures.

Abstract:

In response to the rising rate of treatment admissions related to illicit use of amphetamines (e.g., methamphetamine), this ancillary investigation examined the prevalence of amphetamine use among treatment-seeking, opioid-dependent adults, explored whether amphetamine users were as likely as non-amphetamine users to enroll in opioid-dependence treatment trials, and determined whether amphetamine users manifested greater levels of medical and psychiatric comorbidity than nonusers. The sample included 1257 opioid-dependent adults screened for participation in three multisite studies of the National Drug Abuse Treatment Clinical Trials Network (protocols CTN-0001, -0002, and -0003), which studied the effectiveness of buprenorphine for opioid detoxification under varying treatment conditions. Five mutually exclusive groups were examined, i.e., nonusers, current amphetamine injectors, current amphetamine non-injectors, former amphetamine injectors, and former amphetamine non-injectors Of the sample, 22.3% had a history of regular amphetamine use; of those users, 30.3% reported injection as their primary route. Amphetamine users were as likely as nonusers to enroll in treatment trials. Bivariate analyses indicated elevated rates of psychiatric problems (depression, anxiety, etc.) and medical illnesses (dermatological, hepatic, etc.) among amphetamine users. After adjusting for demographic variables and lifetime use of other substances: current amphetamine users and former injectors showed an increased likelihood of having medical illnesses and hospitalizations; current injectors had elevated odds of suicidal thoughts or attempts; current non-injectors had exhibited elevated odds of anxiety, cognitive impairment, and violent behaviors; and former non-injectors had increased odds of depression.

Conclusions: Treatment-seeking, amphetamine-using, opioid-dependent adults manifest greater levels of medical and psychiatric morbidity than treatment-seeking, opioid-dependent adults who have not used amphetamines, indicating a greater need for intensive clinical management.

Supported by the Duke Clinical Research Institute (CTN DSC 1).

Abstract:

This set of slides features presentations from a symposium at the 2011 APA convention that focused on substance use treatment with ethnic minorities in the National Drug Abuse Treatment Clinical Trials Network. It begins with an overview of the CTN and its aim to improve substance abuse treatment by bridging the gap between practice and research, and then continues with presentations on a variety of ancillary investigations of CTN protocols: a comparison of gender, race/ethnicity, and age groups in people participating in CTN studies; racial/ethnic differences in the rates and correlates of HIV risk behaviors among drug abusers; the relation of racial/ethnic matching to engagement, retention, and treatment outcomes for adolescent substance users; and the relationship between therapist and patient gender/race-matching and substance use outcomes in two motivational therapy trials (CTN-0004 and CTN-0021). Results from each ancillary investigation are presented, along with discussion of the outcomes and study limitations.

Related protocols: CTN-0001, CTN-0002, CTN-0004, CTN-0005, CTN-0006, CTN-0007, CTN-0014, CTN-0021

Abstract:

The focus of this presentation is on the outcomes of medication studies in the CTN and how those outcomes can be applied to treatment in community-based settings. Medication studies in the CTN have included four studies on opioid dependence (buprenorphine vs. clonidine, buprenorphine taper, buprenorphine for adolescents, and the Prescription Opioid Addiction Treatment Study) and two studies on methylphenidate (methylphenidate for smokers with ADHD and methylphenidate for adolescents with ADHD and substance use disorder). Outcomes from each trial are presented, along with implications for community-based treatment providers. Overall, these protocols have demonstrated that medication studies — both straight-forward studies and highly complex ones — can be conducted safely and effectively in community drug abuse treatment programs. Staff members in these programs can be highly enthusiastic about the new therapies, something that aids in implementation, and evidence supports the fact that successful medication trials can lead to increased use of empirically validated pharmacotherapies.

The presentation ends with a look at ongoing and future medication research in the CTN, including buprenorphine for cocaine dependence, long-acting injectable naltrexone for opioid dependence, bupropion for smokers with stimulant dependence, buspirone for cocaine dependence, and treatments for cannabis dependence.

Related protocols: CTN-0001, CTN-0002, CTN-0003, CTN-0009, CTN-0010, CTN-0028, CTN-0030

Abstract:

This study applied item response theory (IRT) and latent class analysis (LCA) procedures to examine the dimensionality and heterogeneity of comorbid substance use disorders (SUDs) and explored their utility for standard clinical assessments, including the Addiction Severity Index (ASI), HIV Risk Behavior Scale (HRBS), and SF-36 quality-of-life measures. The sample included 343 opioid-dependent patients enrolled in two national multisite studies of the National Drug Abuse Treatment Clinical Trials Network (protocols CTN-0001 and CTN-0002). Data were analyzed by factor analysis, IRT, LCA, and latent regression procedures. A two-class LCA model fit dichotomous SUD data empirically better than one-parameter and two-parameter IRT models. LCA distinguished 10% of severe comorbid opioid-dependent individuals who had high rates of all SUDs examined — especially amphetamine and sedative abuse/dependence — from the remaining 90% who had SUDs other than amphetamine and sedative abuse-dependence (entropy = 0.99). Item-level results from both one-parameter and two-parameter IRT models also found that amphetamine and sedative abuse/dependence tapped the more severe end of the latent poly-SUD trait. Regardless of whether SUDs were defined as a continuous trait or categorically, individuals characterized by a high level of poly-SUD demonstrated more psychiatric problems and HIV risk behaviors. In conclusion, a combined application of categorical and dimensional latent approaches may improve the understanding of comorbid SUDs and their associations with other clinical indicators. The LCA approach provides practically useful information for informing more focused interventions by pinpointing specific groups with severe comorbid SUDs; the IRT conceptualization of SUDs as a continuous condition is heuristically consistent with the nature of a medical disorder, and as such, emphasizes screening and early prevention for managing a chronic addiction to avoid more costly consequences. Abuse of sedatives and methamphetamine may serve as a useful marker for identifying subsets of opioid-dependent individuals with needs for more intensive interventions.

Supported by the Duke Clinical Research Institute (CTN DSC 1).

Related protocols: CTN-0001, CTN-0002

Abstract:

The National Drug Abuse Treatment Clinical Trials Network (CTN) has faced many challenges over its first eleven years. This review explores some of these challenges and the paths the CTN took to meet these challenges, including: designing clinical trials that reflect the CTN’s mission and changing public health needs, finding the synergies in the varied expertise of clinical treatment providers and academic researchers, promoting evidence-based practices, and expanding the Network into mainstream medical practices to reach a broader patient population. Included in this exploration are specific examples from CTN clinical trials.

CTN studies have shown that quality clinical trials can be successfully implemented into practice settings unfamiliar with research logistics by taking clinicians’ practical needs and research knowledge level into account. The challenges yet to be faced in the CTN’s efforts to expand opportunities to offer existing treatments to the segment of the drug-abusing population that utilizes mainstream health care seem large, but not as large as the potential for improvements in public health.

Related protocols: CTN-0001, CTN-0002, CTN-0003, CTN-0004, CTN-0005, CTN-0006, CTN-0007, CTN-0009, CTN-0010, CTN-0011, CTN-0013, CTN-0014, CTN-0015, CTN-0017, CTN-0018, CTN-0019, CTN-0020, CTN-0021, CTN-0027, CTN-0028, CTN-0029, CTN-0030, CTN-0031, CTN-0032, CTN-0037, CTCN-0044, CTN-0047, CTN-0048, CTN-0049

Abstract:

Previous work suggests that opioid users have lower health-related quality of life (HRQOL) than patients with more prevalent chronic illnesses such as hypertension or diabetes. Although comparisons with population norms are informative, studies of the correlates of HRQOL for opioid users are needed to plan clinical services. This article reports on a study that tested a conceptual model of the pathways between physiologic factors and symptoms in relation to HRQOL among 344 opioid users participating in the National Drug Abuse Treatment Clinical Trials Network (CTN) studies about buprenorphine (protocols CTN-0001 and CTN-0002). Physical and mental HRQOL were measured by the Short-Form (SF)-36; withdrawal signs, symptoms, and functioning were also measured with validated instruments. Using structural equation modeling, the authors tested hypotheses that medical history directly predicts withdrawal signs and symptoms, and that medical history, withdrawal signs and symptoms, and functioning predict the physical and mental HRQOL latent variables of the SF-36. The study’s results found most hypothesized relationships to be significant, with good model fit. The model explained 34% of the variance in physical HRQOL. In conclusion, the conceptual framework appears valid for explaining variation in the physical and mental HRQOL of opioid users undergoing medically managed withdrawal. Future work should assess whether opioid dependence treatments that are informed by effects of treatment on HRQOL lead to better outcomes, including increases in patients’ motivation to engage in longer-term rehabilitation efforts.

Related protocols: CTN-0001, CTN-0002

Abstract:

Detoxification often serves as an initial contact for treatment and represents an opportunity for engaging patients in aftercare to prevent relapse. However, there is limited information concerning clinical profiles of individuals seeking detoxification, and the opportunity to engage patients in detoxification for aftercare often is missed. This study used data from protocols CTN-0001 and CTN-0002 to examine clinical profiles of a geographically diverse sample of opioid-dependent adults in detoxification to discern the treatment needs of a growing number of women and whites with opioid addiction and to inform interventions aimed at improving use of aftercare or rehabilitation. Gender and racial/ethnic differences in addiction severity, HIV risk, and quality of life were examined. Results found that women and whites were more likely than men and African Americans to have greater psychiatric and family/social relationship problems, and to report poorer health-related quality of life and functioning. White and Hispanics exhibited higher levels of total HIV risk scores and risky injection drug use scores than African Americans, and Hispanics showed a higher level of unprotected sexual behaviors than whites. African Americans were more likely than whites to use heroin and cocaine, and to have more severe alcohol and employment problems. These results highlight the need to monitor an increased trend of opioid addiction among women and whites and to develop effective combined psychosocial and pharmacologic treatments to meet the diverse needs of the expanding opioid-abusing population. Elevated levels of HIV risk behaviors among Hispanics and whites also warrant more research to delineate mechanism and reduce their risky behaviors.

Supported by the Duke Clinical Research Institute (CTN DSC 1).

Related protocols: CTN-0001, CTN-0002

Abstract:

Participant retention is critically important for clinical research studies in the area of addictions. This study, using data from fifteen trials in the National Drug Abuse Treatment Clinical Trials Network, sought to examine predictors of retention in a series of treatment outcome studies. Studies were combined, defining retention through the final follow-up visit, and multivariate logistic regression models were used to assess predictors of study retention, focusing on age, gender, and ethnicity (non-Hispanic White, African American, and Hispanic/Other). Results found no clear pattern, however retention seemed higher in adult pharmacologic trials and lower in sexual risk reduction trials. Younger participants were more likely to drop out and, in comparison to African American participants, non-Hispanic Whites were more likely and Hispanic/Others less likely, to drop out. In terms of gender, no significant difference was found between the sexes, though a significant interaction was discovered between ethnicity and gender in relation to study retention. This interaction was largely driven by Hispanic/Other women (not in methadone treatment), who were approximately 40% less likely to be lost to follow-up than their African American counterparts. The results suggest that strategies focused on improving study retention in younger subjects, and in non-Hispanic females, may be particularly important for increasing participant retention and improving the validity of clinical trial data.

Related protocols: CTN-0001, CTN-0002, CTN-0003, CTN-0004, CTN-0005, CTN-0006, CTN-0007, CTN-0009, CTN-0010, CTN-0011, CTN-0013, CTN-0015, CTN-0018, CTN-0019, CTN-0021