This funding opportunity announcement (FOA) invites research projects that seek to explain the underlying mechanisms, processes, and trajectories of social relationships and how these factors affect outcomes in human health, illness, recovery, and overall wellbeing. Types of projects submitted under this FOA include mechanistic studies that are classified as clinical trials. Mechanistic studies are defined as studies with the objective to understand the mechanism(s) of action of an intervention, a biological or behavioral process, or the pathophysiology of a disease/condition. See NOT-AT-20-001 and NOT-MH-19-006 for examples of clinical trials that are/are not considered mechanistic studies. Clinical trials that propose to influence a clinical outcome, test safety or feasibility of an intervention, demonstrate the clinical efficacy or effectiveness of an intervention, or analyze the effect size of an intervention on clinical outcomes are ineligible for this FOA. Types of studies that should submit under this FOA include clinical trials that assess biomedical or behavioral outcomes in humans for the purpose of understanding the fundamental aspects of phenomena without specific application towards processes or products in mind. Researchers proposing basic science experimental studies involving human participants should consider this FOAs companion for basic experimental studies with humans, TEMP-14931, Research on Health, Wellbeing, Illness, and Recovery (R01 Basic Experimental Studies with Humans Required). Applications proposing studies that include, but are not limited to, model animal research or observational studies involving humans should submit under the companion FOA, TEMP-14934, "Research on Biopsychosocial Factors of Social Connectedness and Isolation on Health, Wellbeing, Illness, and Recovery (R01 Clinical Trials Not Allowed).