strokenet: rationale, overview, objectives, priorities,...
TRANSCRIPT
NIH StrokeNet Overview
• NINDS created StrokeNet in late 2013 (fully funded in 4/2014) to prioritize, harmonize, and efficiently conduct NINDS funded clinical trials in stroke prevention, treatment, and recovery
• 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
• Designed to support early exploratory phase 2 to confirmatory phase 3 trials
• Provides the infrastructure to streamline trials through the use of a centralized IRB and master trial contracts and to provide centralized support for data management, integration, and data sharing
NIH StrokeNet
Census Region: West Midwest South Northeast
UW Medicine/ Harborview Med. Ctr.
NorCal Research RCC
Stanford Stroke Center
Los Angeles-So. California Regional NIH StrokeNET UCSD Stroke Center
U Utah RCC
U Minnesota RCC
U Iowa RCC
U Wisconsin
Chicago Stroke Trials Consortium
Michigan StrokeNet
NIH Cleveland Stroke Trials Collaborative
Ohio State WexnerRCC
U Cincinnati RCC
Vanderbilt U Medical Ctr
Georgia StrokeNet
Miami RCC Gulf Regional Area Stroke Programs
So. Caroline Collaborative Alliance for Stroke Trials
Stroke National Capital Area Network for Research
UPMC Stroke Institute
G. Philadelphia NIH StrokeNet
New England RCC
Stroke Trials Network of Columbia and Cornell
NY City Collaborative RCC
www.NIHStrokeNet.org
Leadership Structure of StrokeNet
www.NIHStrokeNet.org
EXECUTIVE Committee
STEERING Committee
OPERATIONS Committee
NINDS / Scientific Advisory
Leadership
Data
Management
Center
Medical University of
South Carolina
National Coordinating
Center and Central
Pharmacy
University of Cincinnati
Regional Coordinating
Centers ( N = 25 )
Satellite Sites / Clinical
Performace Sites
Protocol Awarded
Centers
NON - Network
CORES
Imaging
Training
ADVISORY
COMMITTEES WORKING
GROUPS
Acute Stroke
Prevention
Rehab / Recovery
DSMB
Central IRB
University of Cincinnati
~284 Hospitals
Ethics and Competing Trials
Minority Recruitment
Interventional Management
Joe Broderick, MD
Yuko Palesch, PhD
University of Cincinnati
College of Medicine (COM)
Department of Neurology and Rehabilitation
Medicine
NCC Operations Center within University of Cincinnati
StrokeNet National Coordinating Center (NCC)
Contact PI (Broderick) Co-PIs (Khatri, Brott, Cramer)
NCC Organizational Chart
Trial Design, Feasibility Assessment, Scientific and Clinical Expertise
Operational Infrastructure
Educational Core (Kleindorfer,
Marshall)
Working Groups
Imaging Core
Feasibility
Advisory Groups
Operational Infrastructure (UC) PI Broderick
NCC Organizational Chart
Contracts and Legal Liaison
(Sparks)
Clinical Research Administrative
Directors Spilker, Frasure
Central IRB (Linke, Brown)
Trial Project Managers
Pharmacy (Dill)
Financial Manager (Carey)
Administrative Specialist
(Beckman)
cIRB liaison (Roll)
Process of Trial Concept to Trial Start
• Trials can arise from Working Groups within StrokeNet or from outside StrokeNet
• Process involves interaction with Protocol PIs along the entire way but with the bulk of the focus of the working groups and Executive Committee on scientific input (not review) and trial feasibility within the network
StrokeNet Trial Development Process
Applicant submits and discusses initial concept with
NINDS
Applicant discusses concept with Working Group and
submits Concept Proposal NINDS ESC Approval
Feasibility review and
development of budget
Submission for Scientific
Peer Review
Council Review
Final Protocol development with Network
cIRB approval GO!!
Trial Process –DEFUSE III As Example
Step Date Step Date Approval NINDS ESC 5/7/2014 Working Group Summary 2/6/2015
Acute Working Group 5/7/2014 Executive Committee Summary 2/9/2015
Feasibility Assessment Completed from Sites
6/13/2014 Submission for NIH Review 3/5/2015
Working Group Summary 6/16/2014 NINDS Council Review 9/10/2015
Executive Committee Summary 6/18/2014
Submission for NIH Review 7/5/2014
Presentation of MR CLEAN 10/29/2014
NIH Review 11/2014
Second Feasibility Assessment Begun
1/16/2015
Feasibility Survey/Population Assessment –Prevention Trial
Feasibility Survey
• Feasibility recommendation to StrokeNet Exec Committee: 122 clinical sites willing to participate and provide approximately 5 subjects per years.
• 81 sites expressed substantial or extreme enthusiasm about participating in this novel and important study.
• 80 StrokeNet sites would be sufficient to meet trial goals to recruit 806 patients over 2 years.
Population Assessment
• Summary of Eligibility Analysis Within a Population: 10.7% of ischemic stroke patients were eligible for this trial within a population.
• Estimation does not include the proportion of patients with atrial cardiopathy, a less common and extremely important exclusion for this study.
• 24% of all ischemic stroke patients had any left atrial enlargement described (which may include the excluded “mild” LAE), of which 46 (2% of all stroke cases) were otherwise eligible for the study.
Trials Currently Underway in the Network
MISTIE INTRACEREBRAL HEMORRHAGE TRIAL Does faster clot removal in ICH give better patient outcomes?
Diffusion and Perfusion Weighted Imaging Evaluation for Understanding Stroke Evolution TRIAL
Trials Submitted for Peer Review = 7
Trial Domain Submitted
DEFUSE 3 (X2) Acute June 2014 & March 2015*
ICTUS 2-3 Acute October 2014
MOST (X2) Acute October 2014 & July 2015
PICASSO Prevention February 2015
ARCADIA Prevention June 2015
*Trial Awarded in mid-September
Trials in Development/Pending Submission = 12 Trial Domain Anticipated submission
IMPACT Acute October 2015
PreLIMBS Acute October 2015
CREST-H (Ancillary study) Prevention October 2015
ICTuS 3 Acute Resubmission in development
PICASSO Prevention Resubmission in development
DOSER Rehab and Recovery In development
C-PAP Prevention In development
SATURN Prevention In development
Tempo-EMS Acute February 2016
ARREST Prevention In development
LARIAT Prevention February 2016
I WITNESS Acute February 2016
2014-2015 Didactic Webinars Date Topic Speaker Institution Moderator Attendance
Aug28 Next Generation Drugs for Neuroprotection
in Acute Ischemic Stroke
B McLaughlin Vanderbilt Tirschwell 66
Sept 25 Thrombolysis in pediatric stroke R Ichord U Penn Tirschwell 79
Oct 30 Neuroimaging Characterization of Brain
Plasticity in Aging and Stroke
V Prabhakaran U Wisc Liebeskind 95
Nov 20 Cell-Based Therapies for Stroke S Savitz UT Houston Marshall 79
Jan 29 Gloves Off for Acute Stroke Management
“New Combatants”: Fellow case
presentations to 2 Stroke Experts
H Adams/G Albers
and Fellows
U Iowa/
Stanford
Kleindorfer 85
Feb 26 Telemedicine in Practice and Research L Schwamm MGH Marshall 131
Mar 26 Aphasia and Language Recovery R Lazar Columbia Marshall 55
April 30 Post Stroke Fatigue K Becker UW Kleindorfer 77
May 28 High Resolution Cerebrovascular Vessel Wall
Imaging
T Hatsukami UW Liebeskind 67
Professional Development Webinars 2015-16
Date Topic Speaker Time Institution Moderator
July 27
Monday
Writing your CV & Biosketch
(updated with new format)
Dawn Kleindorfer 4:00 Cincinnati
Aug 20
Thursday
Approval Process for Medical
Devices in Stroke
Wade Smith 2:00 UCSF Tirschwell
Sept 30
Wednesday
How to Present your Data Enrique Leira 3:00 Iowa Kleindorfer
Oct 20
Tuesday
Creating a Study Budget Joe Broderick
Judy Spilker
1:30 Cincinnati Kleindorfer
Nov 12
Thursday
Grant Writing Steve Greenberg 1:00 MGH Marshall
Medical University of South Carolina (MUSC)
College of Medicine (COM)
Department of Public Health Sciences (DPHS)
NDMC Location
Data Coordination Unit (DCU)
StrokeNet National Data Management Center (NDMC)
Contact PI (Palesch) Co-PI (Zhao)
Clinical Advisor (Jauch)
Operations Director (Dillon)
Neuroimaging Core* Biostatistics Core
Data Management Core Site Monitors
NDMC Organizational Chart
Neuroimaging Advisor (George)
* In conjunction with the NCC
Network Development SOPs Working Groups RCC Site Visits Interaction with Global Networks
Project Development Feasibility Surveys Trial Designs Budgeting Project Development Tracking
Information Management RCC, Clinical Sites, Investigators Regulatory Documents Neuroimaging Tracking
NDMC Infrastructure Work Scope
Pre-Implementation Protocol, CRF, and SAP development Study database setup in WebDCU™ Integration of randomization into WebDCU™
Implementation Data management and QA Site Monitoring Neuroimaging tracking Interim reports and analyses Interaction with DSMB as unblinded statistician Blinded statistical input (if needed)
Post-Implementation Database lock Analyses and publications Submission of Public Use Data Sets (PUDS)
NDMC Project Work Scope
WebDCU™ - a CTMS
We manage:
Study Subjects
Clinical Sites
Overall Project
CRF Data
and the StrokeNet
Central Neuroimaging Repository at LONI
Neuroimaging Collection
Imaging Registration in WebDCU™
Subject Enrollment in WebDCU™
Imaging Upload to LONI
Notification to Central Reader
QA Pass?
Imaging Download and Review by Central Reader
Central Review Data Entry into WebDCU™
NO YES
Challenges
• Balance the portfolio with clinical trials in stroke treatment, prevention and recovery. Competing enrollments between types of trials
• The field and culture of stroke recovery and rehabilitation is new to multicenter clinical trials. Lack of experienced leadership, inclusion of other non-neurology specialties, impact upon variable reimbursement for PT/OT/speech.
• Broader use of Collaborative Research and Development Agreements (CRADA) between NINDS and industry partners
Plans
• Implement trials quickly as they are approved for funding
• Expedite number of high-quality trial proposals – particularly in stroke recovery/rehabilitation.
• Enhance collaborations with international colleagues (global stroke network – trial collaborations), industry (STAIR conference adjacent in time and place to StrokeNet meeting in October), and pre-clinical scientists (possible renewal of focused “Princeton-like” conference – needs funding source).
• Grow and develop educational programs
Top 3 Gaps Acute Treatment
Based on the above, we have forwarded the following top 3 vote getters for priority gaps to the StrokeNet Executive Committee (8 gaps identified by group):
1. Prehospital neuroprotection for ischemic stroke
2. Endovascular mechanical thrombectomy for ischemic stroke in beyond 6h patients with imaging selection
3. Any hyperacute therapy for ICH (top single suggestion pro- coagulants in ICH
4. Six of the 8 gaps are represented by ongoing StrokeNet Trials, already submitted, or submitted by October, 2015.
Bolded = ongoing or submitted trial, or in development within StrokeNet
Top 3 Gaps Prevention 1. Optimizing medical management for secondary stroke prevention including research on innovative systems to maximize delivery of care and strategies to bolster self-management skills, self- efficacy, medication adherence, and lifestyle change. 2. Developing more effective early and long-term interventions for stroke subtype-specific secondary prevention among high risk patients with intracranial atherosclerosis, cardioembolic stroke, small vessel disease (ischemic strokes and intracerebral hemorrhage), and cryptogenic infarcts including personalized pharmacogenetic approaches for antithrombotic medication selection. 3. Improving primary prevention strategies including interventions for subclinical leukoarisosis progression/silent stroke, vascular cognitive impairment, asymptomatic aneurysms, and peri-operative stroke.
Top 3 - Recovery-rehabilitation Gaps
1. Understand and document the effects of activity-based interventions, with particular reference to issues of content, dose, and timing.
2. Establish biomarkers of restorative events
3. Increase the number of viable Recovery & Rehabilitation applications.
Ongoing Clinical Trials in RCCs in 2/2014 (n=245*)
33
21
24
167
Number of Trials
Acute
Prevention
Biomarker
Recovery and Rehabilitation
* 2/2014: Out of the 669 ongoing ‘Stroke Trials’ listed on clinicaltrials.gov
2 – Not approved by ESC 11 - Redirected as not suitable for NIH
StrokeNet
1 - approved for funding
Over 40 projects proposed thus far 28 full concept proposals submitted to NINDS
•Treatment: 10 •Prevention: 8 •Recovery: 10
.
8- Concepts submitted to ESC 6- Approved by ESC 6- Applications submitted for peer-
review
Activities of the Training Core
• Supervision of the RCC Training Programs • Ensure that adequate focus on stroke research
• Education plans with milestones for progress due prior to trainee arrival • All approved last year, with two requiring more information for the core’s review
• Mid-year progress reports • Reviewed, no significant issues noted
• Final Progress Report • Including information about their next position and success in research so far, contact
information
Metrics for Measuring Success of Training Core • Webinar Attendance and Attendee Surveys
• Research Presentations by Trainees
• Final Trainee Survey
• Trainees themselves! • Publications
• Future participation in research • Academic institutions
• Participation in clinical trials/clinical research
• 24/25 of 2014-15 trainees reported their next position was in academia and will be “significantly involved” in research
• Writing/receiving grants
Interactions with Other Networks • NETT – meeting regularly with leadership – collaborations on trials
• NeuroNEXT – supportive enrollment in Rhapsody trial.
• cIRB • Working with cIRB for VAMC for those StrokeNet satellite sites who are part of
StrokeNet – first of its kind • Collaborations with NeuroNEXT, CTSA, and other cIRBs
• AHA • GWTG database – working to incorporate these data as part of data for feasibility
survey of StrokeNet sites (Lee Schwamm, Joe Broderick, Dawn Kleindorfer)
• Global Stroke Alliance • Two meetings in person of national stroke networks leadership. Quarterly meetings
by phone • Planned second meeting with Japanese network in 2016 • Discussing with Australian Stroke Network about DEFUSE III collaboration
Advisory Committees
1) Ethics and Competing Trials Committee (Dr. Jennifer Majersik) – written guideline
2) The Minority Recruitment and Retention Advisory Committee under the direction of B. Boden Albala and Dawn Kleindorfer to assist in the development of strategies to address women and minority recruitment needs in SN grant proposals.
3) The Interventional Advisory Committee was expanded and activated under the direction of Colin Derdeyn and Sam Zaidat to assist in addressing the changes in clinical practice and potential trial design necessitated by the positive findings in the recent endovascular trials.
4) Pediatric Stroke Committee – Chair is Heather Fullerton, MD, and awaiting first potential trial