Maximizing the utility of a single site randomized controlled psychotherapy trial.PURPOSE OF THE RESEARCH:  There is increasing interest in including measures of biological mechanisms as mediators and moderators of treatment outcome in randomized controlled trials (RCT''s) of psychotherapy efficacy. However, examining biological mechanisms is often expensive and budget caps of most major funding agencies have remained stable in recent years. The goal of this manuscript is to describe how a psychotherapy efficacy trial is using a model of collaborative, affiliated grants to maximize resources and the potential knowledge to be gained from a single site RCT. Principal results and conclusions: The trial is an ongoing RCT comparing two psychotherapies for the treatment of concurrent posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) with a sample of treatment seeking veterans. Through collaboration with a team of investigators with independently-funded but affiliated grants, measures of select sleep, neurobiological, and genetic biomarkers were integrated into this single site RCT. This model has allowed us to pose research questions regarding the role of biological mechanisms, maximize the utility of recruitment, and be efficient in maximizing knowledge to be gained in a way that would not be possible solely on the funding of a single site RCT. Challenges of this model include high participant burden in regard to assessment and complicated coordinating procedures among studies. Strategies to address these challenges are described.