PROJECT SUMMARY / ABSTRACT TrialNet's mission is to bring disease modifying therapy to clinical use in type 1 diabetes (T1D) with a primary focus on conducting clinical trials at early stages of disease to prevent or delay clinical onset. TrialNet is an international consortium of twenty-five Clinical Centers and hundreds of Affiliate sites in US, Canada, UK, Sweden, Finland, Germany, Italy, and Australia. These sites together with the TrialNet Coordinating Center (TNCC), the TrialNet Clinical Hub (HUB), and members of our Collaborative Mechanistic Studies Panel (CMSP), (a) conduct natural history studies to describe the progression of T1D and identify individuals for clinical trials, (b) conduct clinical trials of disease modifying therapy both prior to and after clinical diagnosis, and (c) increase the scientific value of trials through mechanistic studies involving investigators within and external to TrialNet. The mission of the Type 1 Diabetes TrialNet Hub is to increase the efficiency of critical Network activities by supporting collaborative and innovative approaches for screening, recruitment, retention, trial development and implementation, and dissemination of results. With considerable success during the previous grant period, this application describes our proposal to continue to serve as the Diabetes TrialNet Clinical HUB. We focus on three areas; activities to (a) enhance risk screening to identify at-risk individuals, (b) enhance enrollment and retention in clinical trials, and (c) enhance clinical administration to effectively implement TrialNet's goals.