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Over the past two decades, the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) has made major contributions to progress in substance use treatment research. However, contributions to research addressing the considerable medical and mental health comorbidities of substance use, which can impede treatment efficacy and compromise health, have been emphasized less. In this Commentary, we review the contributions of CTN studies focused on medical comorbidities, initially centered on the HIV epidemic in people who use drugs, and subsequently broadening to address hepatitis C and life-threatening bacterial infections; as well as mental health comorbidities, especially post-traumatic stress disorder, attention-deficit/hyperactivity disorder, and suicidality. These studies demonstrate that comorbidities assessments and treatment can be feasibly implemented in substance use treatment programs and, conversely, that substance use assessments and treatments can be feasibly implemented in clinical care sites. We highlight the NIDA CTN Data Share as an invaluable resource for secondary analyses of comorbidities using data from CTN substance use treatment protocols and provide examples of its use. We describe the work of the CTN Comorbidities of Substance Use Special Interest Group (SIG), formerly known as the HIV SIG, as an example of the role that SIGs can play in facilitating CTN research in areas of emerging significance. We emphasize the importance of implementing a “whole person” approach—one that integrates both substance use and comorbidities outcomes. We identify promising opportunities for conducting this research by studying strategies for integrating prevention, screening, linkage, treatment, adherence, and retention support for comorbidities into substance use disorder (SUD) treatment venues; as well as strategies for integrating SUD treatment into primary care venues, hospitals, and other non-SUD clinical settings.

In addition to the studies underway, CTN participants are planning multi-site clinical trials with emerging results that address HIV/AIDS. The CTN has a HIV/AIDS Special Interest Group (SIG) that meets regularly to discuss study ideas and policy approaches. The SIG provides a supportive place to discuss HIV research related to the CTN, share information with each other about opportunities and developments, promote AIDS ideas and research in the CTN, and link CTN research with the AIDS Research Office of NIDA. The SIG periodically reviews and prioritizes study ideas before they work their way up the organizational hierarchy, and, in the latest CTN Call for Concepts, had developed approximately ten suggestions for HIV-related research studies.

Several studies using the CTN ?platform? have also been fielded with external resources. The term ?platform study? describes extramurally funded research that builds on the CTN infrastructure. Studies can add a dimension to a CTN trial, test an intervention by using the infrastructure of the CTN, focus on CTN programs to understand an issue, include CTN programs in data collection, or provide training or career development in the CTN. Extramurally funded platform studies are addressing such issues as models of care for HIV and hepatitis, integrating medical treatment with addiction treatment, and improving adherence to HIV medications.