Coordinator Webinar and Round Table Discussion July 25, 2018

Coordinator Call Announcements and Reminders Next Coordinator Webinar : Next Coordinator Call August 29th, 2018. Sleep Smart Study Team will host the next round table discussion. Today’s Roundtable Hosts: Scott Janis and Joe Broderick. To join Coordinator Webinars: https://nihstrokenet.adobeconnect.com/coordinator/ Please enter as a guest, then add your first and last name or email address. For Audio: Dial-In Number: (877) 621-0220 Passcode 434578. Upcoming StrokeNet Meetings: Plan Ahead: Montreal World Stroke Conference, October 16th, 2018. NCC will reimburse for one night stay at $250.

Project Updates TELE-REHAB Closed to Enrollment: Study Updates: Study Project Managers: Lucy Dodakian, MA, OTR/L Judith Spilker, RN, BSN Study Investigator: Steve Cramer, MD Data Manager: Kavita Patel

Project Updates i-DEF Closed to Enrollment: Study Updates: Study Project Manager: Jessica Griffin Study Investigator: Magdy Selim, MD

Project Updates DEFUSE 3 Closed to Enrollment: Study Updates: Study Project Manager: Stephanie Kemp, BS Janice Carrozzella, MSN, CNP, RT(R), CCRA Study Investigator: Greg Albers, MD Data Manager: Jessica Griffin

Project Updates CREST 2 Study Updates: Study Project Manager: Mary Longbottom, CCRP, CREST Director for Data Quality  Study Investigator: Tom Brott, MD

Project Updates ARCADIA Study Updates: Study Project Manager: Irene Ewing, RN, BSN Study Investigator: Hooman Kamel, MD; Mitch Elkind, MD Data Manager: Faria Khattak and Holly Pierce

Project Updates Sleep Smart Sleep Smart PI: Devin Brown MD Project Manager: Kayla Gosselin Joelle, Sickler

Project Updates MOST Most: Project Manager: Teresa Murrell-Bohn Iris Deeds

MOST Study Team Principal Investigators (Lead) Opeolu Adeoye, MD, MS, University of Cincinnati Andrew Barreto, MD, MS, University of Texas-Houston Jim Grotta, MD, Memorial Hermann Hospital-Texas Medical Center, Houston Joe Broderick, MD, University of Cincinnati Colin Derdeyn, MD, University of Iowa University of Cincinnati Clinical Coordinating Center S. Iris Deeds, CCRP – Lead Trial Coordinator (deedsss@ucmail.uc.edu) NIH StrokeNet National Coordinating Center Teresa Murrell-Bohn, RN, CCRC – NCC MOST Project Manager (murreltm@ucmail.uc.edu)

Project Updates Recognized NIH Trials That remain open to enrollments: Study Updates: SHINE Project Manager: Heather Haughey

NCC/NINDS Updates NCC Staff Members: Joe Broderick, PI Jamey Frasure, Co-Director Judith Spilker, Co-Director Sue Roll, CIRB Liaison Keeley Hendrix, CIRB Diane Sparks, Contracts Jeanne Sester, Training Coordinator Mary Ann Harty, Finances Rose Beckmann, Administration Joanna Vivalda, NINDS Scott Janis, NINDS

Data Management Center Updates WebDCU/MUSC Team: Yuko Palesch, PI Wenle Zhao, PI Catherine Dillon, Operations Mgr. Jessica Griffin, Project Mgr.

CIRB Updates CIRB Team Members: Sue Roll, CIRB Liaison Keeley Hendrix CIRB Coordinator Jo Ann Behrle CIRB HPA

Roundtable Discussion Today’s Roundtable Discussion: A look back over the past 5 years of StrokeNet and looking into the future.  Today’s Hosts: Scott Janis, PhD Program Director Division of Clinical Research National Institute of Neurological Disorders & Stroke Joseph P. Broderick, M.D. PI NCC StrokeNet Director – University of Cincinnati Neuroscience Institute

NINDS view from 30k feet July 25, 2018 Scott Janis NINDS What StrokeNet is Overview of structure and activities Efforts with recovery and rehab

Public Health Burden of Stroke Stroke is the Fifth Leading Cause of Death in the U.S. 6.8 million Americans have had a known stroke; almost 800,000 new strokes each year (~23% are recurrent strokes). The aging of the US population is on course to lead to a 21.9% increase in prevalence of stroke by 2030. Hypertension and atherosclerosis are the most common treatable risk factors for stroke, cognitive decline and dementia. “Silent strokes” can be seen in 6% - 28% of older people, and are associated with cognitive decline and dementia. White matter disease can be seen in 40-80% of older people, and are associated with hypertension and risk of cognitive decline and dementia. Nearly half of people ≥65 years old have cognitive deficits 6 months after an ischemic stroke

NIH Investment in Stroke Research NINDS - stroke and cerebrovascular biology Overall NIH invested $288M in Stroke research FY 2015

Acute Treatment Recovery Prevention Reperfusion Hemostasis Genetics Athero research Genetics Epidemiology Behavior change Cerebrovascular biology Recovery Neuroplasticity Biology of Repair post-Injury Neural Regeneration Acute Treatment Hemostasis Neuroprotection Reperfusion

Clinical Studies of Highly Promising Treatments Prevention Prevention of Vascular Cognitive Impairment (VCI) Imaging Biomarkers in Stroke Prevention: From Bench to Bedside Expediting High Priority Comparative Effectiveness Research (CER) Trials in Stroke Prevention Treatment Preclinical and Clinical Studies to Improve Early Reperfusion Therapy and Establish Limitations of Late Reperfusion Therapy Preclinical and Clinical Studies to Achieve Robust Brain Protection Expand and Integrate Existing Stroke Trial Networks to Accelerate Translation Recovery Translational Research Using Neural Interface Devices for Stroke and Other Neurologic Disorders Program for Translational Research Targeting Early Recovery after Stroke in Humans Theme across all 3 areas was need for infrastructure Cross-cutting Accelerate the Translation of Stroke Research in Preclinical Animal Models into Clinical Studies of Highly Promising Treatments

$50k/year/hub for training Infrastructure Total Cost- ~$10million/year Established in 2013 29 regional centers (24 funded) with 400 satellite stroke hospitals, a coordinating center, and a data coordinating center Small and large clinical trials and research studies to advance acute stroke treatment, stroke prevention, and recovery and rehabilitation. $50k/year/hub for training Infrastructure Total Cost- ~$10million/year Census Region: West Midwest South Northeast Stanford UCLA/USC UCSD U Utah U Minnesota U Iowa Northwestern U at Chicago U Michigan Case Western Reserve U U Cincinnati Emory U Miami U Texas Houston Medical University South Carolina Medstar Health/NIH and U Virginia U Pittsburgh U Pennsylvania Massachusetts General Hospital Columbia and Cornell UW Medicine U Wisconsin Yale U and Brown U NY City Collaborative RCC UCSF Ohio State Washington U Wake Forest U Vanderbilt U Alabama Renewal RCC NINDS created StrokeNet in 2013 to better support our clinical stroke program by maximizing our ability to prioritize, harmonize, and efficiently conduct clinical trials in stroke prevention, treatment, and recovery The network is a direct response to the recommendations of the Stroke Progress Review Group and NINDS Stroke Planning efforts in 2012 that identified a need and the opportunity to establish a stroke trial network infrastructure The network is designed to support early exploratory phase 2 to confirmatory phase 3 clinical trials Committed cost of Infrastructure each year including indirect’s is $ 10M. The StrokeNet replaced the previous costs of the SPOTRIAS program which cost the NINDs approximately the same $13M a year in total cost to support 7 extramural academic Stroke Centers. New RCC Legacy RCC Coordinating Center & RCC http://nihstrokenet.org/

The Stroke Network Vision: Increased trial efficiency Balanced, prioritized set of early phase and phase 3 trials in prevention, treatment and recovery Provides an efficient path for phase 2 moving to phase 3 Allows the logical ordering of trials that enter into network and create a pipeline of future trials for the network Stable infrastructure and research capacity Improved team research among different subspecialties Stable funding for research effort, fellowship training Improved data sharing Single data center with uniform governance for data access Fosters the use of CDEs Coordination and public-private partnerships with non-profits, industry, and international partners Manages trials that compete for the same patient groups Established upon the commitment to consider ALL eligible stroke patients for a trial Trains the next generation of Stroke clinical researchers

Teamwork is the Solution Stroke Coordinators New Investigators Translational Stroke Science Informatics NeuroSurgery Statisticians Stroke recovery Vascular Neurology Neurointerventional Neuropathology Emergency care Non-profit Stroke Associations Industry Epidemiology Health Technology Neuroimaging International partners FDA PCORI/AHRQ Pediatrics Patient Prevention Treatment Recovery

Goals of the Network To be the leading platform for stroke trials in the U.S. and globally To reduce the burden of stroke in the U.S and globally

Recently Approved Trials Current Trials Domain PI SLEEP-SMART Sleep for Stroke Management and Recovery Trial Prevention/Recovery Devin Brown (Contact PI) Ronald Chervin MOST Multi-Arm Optimization of Stroke Thrombolysis Stroke Trial Acute Ope Adeoye Andrew Barreto Jim Grotta Joe Broderick TRANSPORT 2 Transcranial direct current stimulation for Post-stroke motor Recovery - a phase II study Recovery Wayne Feng (Contact PI) Gottfried Schlaug SATURN Statins use in intracerebral hemorrhage patients Prevention Magdy Selim (Contact PI)

(ancillary to CREST2 trial) Prevention (Ancillary) Ancillary Studies Study Domain PI CREST H CAROTID REVASCULARIZATION AND MEDICAL MANAGEMENT FOR ASYMPTOMATIC CAROTID STENOSIS TRIAL – Hemodynamics (ancillary to CREST2 trial) Prevention (Ancillary) R. Marshall, MD

Year ahead Renewals – new awards in Aug Bring in new centers World Stroke Congress – StrokeNet/GAINS invited session Recovery Workshop in the Fall New trials in the pipeline Lot’s of work ahead!!!

What We Need from Study Coordinators Help to build teams within RCC and internally within RCC headquarters Recruitment – best practices, what is helping, what are the barriers – share with other coordinators and with PIs. Problem solve administrative delays at your sites. Do tasks in parallel, not serially (example trial documents for investigators while working through IRB). Build relationships within your institution of people who do the other jobs (e.g. contracts, cIRB). Make use of your PI

Joseph P Broderick, MD Principal Investigator National Coordinating Center

Performance Metrics WebDCU Dashboard Numbers Enrollment - Number of subjects enrolled Retention - Percent of participants not retained Regulatory Document Collection - Percent of outstanding documents Case Report Collection- percent of outstanding documents CIRB Submission - Time from receiving the CIRB packet to submission is less than 90 days CTA Execution - Time from receiving the CTA to execution is less than 45 days

Performance Metrics Data Reported on the Quarterly Activity Report (QAR) Number of QARs submitted on time Self-reported but confirmed by NCC, participation in network activities such as working groups, relevant StrokeNet calls, and in-person meetings Self-reported but confirmed by NCC, participation in StrokeNet educational activities including faculty/trainees/staff presentations, and outreach to SS/PS

Goals of Next Five Years 6-8 ongoing Phase II and Phase III trials. Would like a few smaller trials if possible since large definitive trials require a lot more resources. Should provide more work at RCCs/sites. Continued grow infrastructure to address these trials ( 3 trials with 100+ sites and 4 if include CREST). Budgets for newer trials will have more infrastructure costs. Continued success with clinical research and educational program for stroke fellows and educational presentations for fellows, coordinators, and faculty.

How StrokeNet will be Judged Overall Trials funded and completed How many trials submitted and funded? Did we meet planned targeted recruitment and time to recruit? Did the trial change or confirm practice? How impactful? Did we address all three areas – prevention, recovery and acute stroke? Did the financial investment for completed trials compare well to financial investment in period prior to StrokeNet? If you assume first two years is start-up, what is the return on investment? Comparison of costs of stroke trials by NIH as compared to industry – that is probable best measure of return on investment (example POINT vs. SOCRATES). Educational programs and graduated fellows

General Information and Reminders Agenda items for Montreal Meeting. Presenters for upcoming Meetings/Coordinators Calls. SPLASH due August 1 Confirmed Montreal Managers Breakout Session Meet and Greet the evening before the meeting (time and place TBD). RPPR reports due Review sites FWA for expiration dates and name changes. MTA and RA amendments coming soon.