The Michigan SIREN Collaborative, (MI-SIREN) is organized around a strong network of research universities and hospitals, including 2 of 17 previously NIH funded research networks (Wayne State University (WSU) and Henry Ford Health Systems, Neurological Emergencies Treatment Trials [NETT] Networks) and the University of Michigan hospitals (bringing patient enrollment capabilities, CTSA support and the large clinical trials network management expertise of the overall NETT coordinating center). Based out of the Detroit Receiving Hospital (DRH), a seasoned and highly successful clinical trial site, the WSU/DRH hub encompasses 8 primary spokes situated within 6 sizeable health care systems affiliated with four major research universities. MI- SIREN’s regionally aligned spoke network touches 5,000,000 lives (60% of Michigan’s population) accounting for 1.1 million ED visits in 2015. Therefore each MI-SIREN site is capable of enrolling a large number of patients with acute and emergent medical conditions. Due to our innovative practices like a three-tiered enrollment system, centralized training, shared employees with designated research duties and mobile intervention teams, our hub and spokes have consistently been leading enrollers in clinical trials including those requiring pre-hospital recruitment and exception from informed consent (EFIC). The latter is facilitated by our tight collaboration with EMS divisions in metropolitan Detroit, Ann Arbor, and Grand Rapids. In addition to a track record of outstanding productivity, we have the strategic ability to enrich the diversity of the SIREN network, providing unique access to the entire population of Detroit, MI, a city of approximately 680,000 that is 82% African American, and highly under resourced (49.8% below poverty level), a population which we have exceptional rates of patient retention. Beyond this, MI-SIREN will provide substantial expertise to the SIREN network itself with our team of collaborators, many of whom are recognized leaders in emergency care within specific content areas such as neurology, cardiology, pulmonology, neurosurgery, trauma surgery, cardiothoracic surgery, hematology, anesthesiology, and critical care. Because of this, MI-SIREN is also well positioned to serve as an active pipeline for innovative research ideas and important grant submissions that would utilize the SIREN network as enrolling sites. In summary, MI-SIREN is a consortium that will provide high-quality enrollment of large numbers of patients in important clinical trials of many emergency conditions and has the academic prowess to design, obtain funding for, and conduct important clinical trials that are key to the overall SIREN mission and concept. OMB No. 0925-0001/0002 (Rev. 03/16 Approved Through 10/31/2018) Page 1 Continuation Format Page

The research produced by the Michigan SIREN Collaborative will produce critical knowledge regarding the treatment and stabilization of life-threatening emergent conditions, particularly in under-resourced populations. Further, the proper treatment of these acute conditions will lead to significantly reduced long-term disabilities and improve the overall quality of life.