Strategies to Innovate EmeRgENcy Care Clinical Trials Network SIREN

SIREN Overview SIREN will enable conduct of high-quality, multi- site clinical trials to improve the outcomes for patients with neurologic, cardiac, respiratory, hematologic and trauma emergency events. SIREN consists of: Clinical Coordinating Center (CCC) Data Coordinating Center (DCC) 11 Clinical Centers with affiliated satellites (Hubs and Spokes)

H H H H H CCC DCC H H H H H

SIREN Overview Trans-federal collaboration Funding: NINDS, NHLBI, NCATS Consulting: OECR, CCCRP in USAMRMC/DoD Combines resources for emergency care research across federal agencies Draws on experience from NETT, ROC and CCCRP to combine the best features

SIREN Objectives Network capable of supporting at least 4 concurrent large (>1,000 patients), simple pragmatic trials In ED and pre-hospital emergency settings. Neurological (except stroke), cardiovascular, pulmonary, hematological, trauma. High Performance Rapid initiation, enrollment, data base lock and analysis Quality: expert leadership, mentorship, quality Cost Effective: Rapid network formation, financial support related to trial performance Points that could be made: Trial initiation rapid due to cIRB, master contracts. NN able start up trial in about 8 weeks. Mentorship – experts from CCC, DCC and Hubs able to mentor first time Pis Rapid network formation – drawing on NCATS Quality – programs at Hub, CCC level. Also SIREN Federal Committee will review every 1-2 years (NHLBI to lead with their methods) Financial support related to performance – through annual reviews of milestones and metrics with NINDS, through per patient payment system during trials which will include component of support for utilization of SIREN infrastructture

SIREN New Trial integrated logistics CCC: central IRB, master trial contracts, overall enrollment, recruitment plan. DCC: standardized CRFs, efficient and user friendly data collection methods, risk based monitoring, efficient data base lock. Hubs and Spokes: access to large diverse population, local enrollment and recruitment plan, strong relationship with EMS, and with specialists and subspecialists.

SIREN Staff at NIH & DoD/USAMRMC NIH Office of Emergency Care Research Dr. Jeremy Brown NCATS Dr. Todd Wilson Dept. of Defense Lt. Col. Jennifer Hatzfeld NINDS Dr. Clinton Wright Dr. Robin Conwit Dr. Scott Janis Ellen Rosenberg Shanta Rajaram NHLBI Dr. George Sopko Dr. Renee Wong  

Central IRB, Central contracting, The SIREN Network CCC DCC NCATS CTSA Central IRB, Central contracting, Monitoring NHLBI NINDS PARTNERS 11 Hubs With spokes OECR DoD I learned that ROC was ending and would not be re-funded, and I learned that NETT was ending. I took the time because you’ve got an office that’s here to focus on this kind of thing, and that allowed me to use my time to work on creating a new trans-federal research network. NCATS

SIREN Sites Census Region: West Midwest South Northeast U Washington UCSF U Colorado UCLA UC Davis U Utah U Minnesota Med Coll Wisconsin Washington Univ Wayne State U Cincinnati Emory MUSC DCC Hopkins U Pitt Philadelphia MGH Temple

Pathway for New Trial PI applies through NINDS usual PI brings proposal to SIREN executive committee for full discussion SIREN executive committee finds proposal suitable for SIREN network Area of study falls within both NHLBI and NINDS Area of study falls within NINDS within NHLBI PI applies through NINDS usual mechanism for clinical trial PI applies through NHLBI usual mechanism for clinical trial

http://grants.nih.gov/grants/guide/notice- files/NOT-OD-16-094.html Final NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research sIRB is the selected IRB of record that conducts the ethical review for participating sites of the multi-site study NOT-OD-16-094 and NOT-OD-16-109 http://grants.nih.gov/grants/guide/notice- files/NOT-OD-16-094.html Guidance on how costs associated with sIRBs may be charged as direct versus indirect costs can be found in Guide Notice NOT-OD-16-109

New FOAs for Investigator-Initiated Phase II and Above Multi-site Clinical Trials (PAR-16-300 and PAR-16-301) - Frequently Asked Questions January 18, 2017 https://www.nhlbi.nih.gov/research/funding/new-foas- investigator-initiated-phase-ii-and-above-multi-site-clinical- trials-par-16-300-and-par-16 The NIH requirement for a single IRB on studies it funds applies to all competing grant applications (new, renewal, revision, or resubmission) with receipt dates on or after May 25, 2017.   Ongoing, non-competing awards will not be expected to comply with this policy until the grantee submits a competing renewal application.  The NHLBI FOAs for multi-site clinical trials will be updated in the future to reflect the new requirement and its effective date.  In the meantime, applicants may consider the use of a single IRB in advance of this policy’s effective date.