StrokeNet: Rationale, Overview, Objectives, Priorities, Status. Joe Broderick Yuko Palesch

Transcription

1 StrokeNet: Rationale, Overview, Objectives, Priorities, Status Joe Broderick Yuko Palesch

2 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

3 NIH StrokeNet UW Medicine/ Harborview Med. Ctr. U Minnesota RCC Chicago Stroke Trials Consortium NIH Cleveland Stroke Trials Collaborative NorCal Research RCC Stanford Stroke Center U Utah RCC U Iowa RCC U Wisconsin Michigan StrokeNet Ohio State WexnerRCC U Cincinnati RCC UPMC Stroke Institute New England RCC Stroke Trials Network of Columbia and Cornell NY City Collaborative RCC G. Philadelphia NIH StrokeNet Stroke National Capital Area Network for Research Los Angeles-So. California Regional NIH StrokeNET UCSD Stroke Center Vanderbilt U Medical Ctr Georgia StrokeNet So. Caroline Collaborative Alliance for Stroke Trials Gulf Regional Area Stroke Programs Miami RCC Census Region: West Midwest South Northeast

4 Leadership Structure of StrokeNet Central IRB University of Cincinnati NINDS / Scientific Advisory Leadership ~284 Hospitals Regional Coordinating Centers ( N = 25 ) Satellite Sites / Clinical Performace Sites Protocol Awarded Centers NON - Network National Coordinating Center and Central Pharmacy University of Cincinnati Joe Broderick, MD Data Management Center Medical University of South Carolina Yuko Palesch, PhD EXECUTIVE Committee STEERING Committee OPERATIONS Committee DSMB WORKING GROUPS Acute Stroke Prevention Rehab / Recovery CORES Imaging Training ADVISORY COMMITTEES Ethics and Competing Trials Minority Recruitment Interventional Management

5 StrokeNet Hospitals

6 StrokeNet Population Coverage by Group and Distance

7 National Coordinating Center

8 NCC Operations Center within University of Cincinnati University of Cincinnati College of Medicine (COM) Department of Neurology and Rehabilitation Medicine StrokeNet National Coordinating Center (NCC)

9 NCC Organizational Chart Contact PI (Broderick) Co-PIs (Khatri, Brott, Cramer) Trial Design, Feasibility Assessment, Scientific and Clinical Expertise Working Groups Imaging Core Feasibility Advisory Groups Operational Infrastructure Educational Core (Kleindorfer, Marshall)

10 NCC Organizational Chart Operational Infrastructure (UC) PI Broderick Clinical Research Administrative Directors Spilker, Frasure Central IRB (Linke, Brown) cirb liaison (Roll) Financial Manager (Carey) Contracts and Legal Liaison (Sparks) Trial Project Managers Administrative Specialist (Beckman) Pharmacy (Dill)

11 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

12 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!!

13 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

14 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.

15 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

16 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

17 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

18 NIH StrokeNet Training Core

19 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

20 Professional Development Webinars Date Topic Speaker Time Institution Moderator July 27 Monday Aug 20 Thursday Sept 30 Wednesday Oct 20 Tuesday Nov 12 Thursday Writing your CV & Biosketch (updated with new format) Dawn Kleindorfer 4:00 Cincinnati Approval Process for Medical Wade Smith 2:00 UCSF Tirschwell Devices in Stroke How to Present your Data Enrique Leira 3:00 Iowa Kleindorfer Creating a Study Budget Joe Broderick 1:30 Cincinnati Kleindorfer Judy Spilker Grant Writing Steve Greenberg 1:00 MGH Marshall

21 National Data Management Center (NDMC)

22 NDMC Location Medical University of South Carolina (MUSC) College of Medicine (COM) Department of Public Health Sciences (DPHS) Data Coordination Unit (DCU) StrokeNet National Data Management Center (NDMC)

23 NDMC Organizational Chart Contact PI (Palesch) Co-PI (Zhao) Neuroimaging Core* * In conjunction with the NCC Operations Director (Dillon) Biostatistics Core Data Management Core Neuroimaging Advisor (George) Site Monitors Clinical Advisor (Jauch)

24 NDMC Infrastructure Work Scope 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

25 NDMC Project 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)

26 WebDCU - a CTMS We manage: CRF Data Study Subjects Clinical Sites Overall Project and the StrokeNet

27 Compliance with Common Data Elements (CDE)

28 Central Neuroimaging Repository at LONI Subject Enrollment in WebDCU Notification to Central Reader Neuroimaging Collection NO YES Imaging Download and Review by Central Reader Imaging Registration in WebDCU Imaging Upload to LONI QA Pass? Central Review Data Entry into WebDCU

29 NDMC Biostatistical Core Randomization in WebDCU

30 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

31 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

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33 NIH StrokeNet Working Groups by Domain

34 NIH StrokeNet NCC Cores

35 Bolded = ongoing or submitted trial, or in development within StrokeNet 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 procoagulants in ICH 4. Six of the 8 gaps are represented by ongoing StrokeNet Trials, already submitted, or submitted by October, 2015.

36 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.

37 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.

38 Ongoing Clinical Trials in RCCs in 2/2014 (n=245*) Number of Trials Acute Prevention Biomarker Recovery and Rehabilitation * 2/2014: Out of the 669 ongoing Stroke Trials listed on clinicaltrials.gov

39 Single RCC Studies versus Multi-Center Studies (n=245)

40 Over 40 projects proposed thus far 28 full concept proposals submitted to NINDS Treatment: 10 Prevention: 8 Recovery: Concepts submitted to ESC 6- Approved by ESC 6- Applications submitted for peerreview 2 Not approved by ESC 11 - Redirected as not suitable for NIH StrokeNet 1 - approved for funding.

41 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

42 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 trainees reported their next position was in academia and will be significantly involved in research Writing/receiving grants

43 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

44 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