The Clinical and Translational Science Awards Program Trial Innovation Network (TIN) is a collaborative initiative aimed at addressing critical roadblocks in the design and implementation of multi-center clinical trials. The goal of the TIN is to execute trials better, faster, and more cost-efficiently, as well as serve as a national laboratory to study, understand, and innovate the process of conducting multi-center clinical trials. The purpose of the issuance of the Next Generation of the TIN Notice of Funding Opportunity (NOFO) is to advance the science of clinical trials by developing and implementing innovative solutions to address challenges at the clinical trial and trial network levels. Topics of interest include, but are not limited to, safety monitoring tools and resources, trial leader training and mentorship, digital health technologies, genomic capacity, and disease progression modeling.