The ability to effectively study and develop innovative treatments for acute critically ill or injured patients remains challenging. Many of these devastating conditions occur infrequently while time-sensitivity of treatments challenge the capacity to obtain prospective informed consent, impeding the ability to enroll large numbers of patients into clinical trials. Yet, the current therapies for many of these devastating conditions are often understudied or unsatisfactory. To this end, the Strategies to Innovate Emergency Care Clinical Trials network (SIREN) provides a national structure to pool resources to address these challenges and advance emergency care. In this proposal we seek to continue our contributions to the SIREN network. These contributions include high numbers of high quality patient enrollments to all funded clinical trials, innovation and dissemination of pragmatic, cost-effective, and ethical advances in the conduct of emergency care research, support of prehospital and Exception From Informed Consent (EFIC) study procedures, and training of the next generation of emergency care clinical trialists. The proposed Upper Midwest hub represents a growth of the prior University of Minnesota hub, with expanding reach and inclusion of sites across the Midwest with a focus on growing rural and teleresearch capacity. Our hub brings academic depth and breadth across wide domains of acute critical care, pre-hospital and emergency research. Hub leadership is experienced in the spectrum of acute care clinical research, pre-hospital research, the use of Exception from Informed Consent for acute critical care clinical trials, positioning us well to conduct all manner of trials supported by the network, while the multidisciplinary specialties needed to collaborate for successful implementation of SIREN are well aligned with collaborative arrangements beyond traditional academic departments.