Applying to the NeuroNEXT Network

1. Applying to the NeuroNEXT Network Webinar for Academic Investigators January 6th, 2011 Christopher Coffey, PhD, Merit Cudkowicz, MD, MSc, and Elizabeth McNeil, MD, MSc

2. Webinar Instructions • Please note the dashboard on the right side of the screen • All attendees are in listen – only mode • During the Q&A session, please use the raise hand function to ask a question • Once called on, your line will be un-muted • If the audio function fails for whatever reason you may type your question into the chat box

3. Agenda • NeuroNEXT Concept and Structure • Applying to NeuroNEXT • What CCC and DCC Contribute to the Protocol Workflow • Q & A

4. NeuroNEXT Concept and Structure Merit Cudkowicz, MD, MScPrincipal Investigator, NeuroNEXT Clinical Coordination Center (CCC)

5. NeuroNEXT Goals Test highly promising therapies in phase II clinical trials, increasing the impact of NINDS funded clinical research Accelerate drug development through an established clinical trials infrastructure Decrease the time/cost between trial design and trial completion Coordinate public/private sector efforts by leveraging NINDS’ existing relationships with academic investigators and patient advocacy groups and engage industry participation

6. NeuroNEXT: Network Designed to Efficiently Conduct Phase II Clinical Trials • Central IRB • Master Contract • 25 experienced, well trained sites throughout the United States • Experienced Clinical and Data Coordinating Centers to help investigators bring new therapies forward

7. NeuroNEXT Network Infrastructure • NIH/ NINDS • Elizabeth McNeil, MD, MSc • Claudia Moy, PhD • Clinical Coordinating Center • Massachusetts General Hospital • Merit Cudkowicz, MD, MSc • Data Coordinating Center • University of Iowa • Christopher Coffey, PhD

8. Clinical Study Sites (Adult/Pediatrics) Albert Einstein College of Medicine-Yeshiva Columbia-Cornell Emory Massachusetts General Hospital Northwestern University Ohio State University Oregon Health and Science University Swedish Health Services (Seattle) SUNY (Buffalo, Downstate, Upstate, and Stony Brook) University of Alabama, Birmingham University of California, Davis UCLA University of Cincinnati University of Colorado, Denver University of Kansas University of Miami University of Pittsburgh University of Rochester University of Utah University of Virginia University of Texas, Dallas Vanderbilt Washington University in St. Louis

9. NeuroNEXT Coordinating Centers and Clinical Sites

10. Applying to the Network Elizabeth McNeil, MD, MScNational Institute of Neurological Disorders and Stroke

11. Why Apply To use NeuroNEXT • Allows access to NeuroNEXT infrastructure • Efficient start up • Pre-existing master trial agreements for all 25 site • Central IRB review administered through NeuroNEXT CCC • Assistance with protocol development

12. Now Accepting Applications! • Three possible mechanisms: • Academic investigators: • NeuroNEXT Clinical Trials (U01) (PAR-11-343). • Upcoming Due Dates: April 2, August 2, and December 3, 2012 • Industry: • NeuroNEXT Clinical Trials (U01) (PAR-11-343); OR • Expedited access to NeuroNEXT expertise and infrastructure through the NeuroNEXT Infrastructure Resource Access (X01) (PAR-11-344) • Small businesses: • NeuroNEXT Clinical Trials (U01) (PAR-11-343); OR • Small Business Program: NeuroNEXT Small Business Innovation in Clinical Trials (U44) (PAR-11-345)

13. What To Do First… • Contact Elizabeth McNeil, MD at NINDS • Complete Concept Form, submit to NINDS • NINDS initial review to determine if proposal meets goals and missions of NeuroNEXT • If yes, proposal sent to NeuroNEXT Executive Committee (NEC) for Network feasibility review • If no, NINDS informs Protocol PI and discusses other funding options • Send in Concept Form early (at least 3 months before plan to apply for grant); earlier better

14. NeuroNEXT Decisions • NEC Network feasibility • Protocol PI works with CCC-DCC Protocol Working Group to develop Protocol Synopsis and draft budget • Synopsis and draft budget review by External Science Committee • Full protocol and grant development • Regulatory submission at least 31 days prior to grant submission (as needed) • Grant submission

15. Grant Applications Must Include… • Compelling scientific evidence for evaluating the proposed investigational agent in the disease under study • Proposed methodology for testing whether the investigational agent has the expected biological effect in study patients • Documentation of an active IND/IDE for the investigational agent or IND exemption, if applicable

16. Grant Applications Do Not Need… • Investigator Brochures • CMC information • Safety toxicology information • Clinical pharmacology information other than justification of the proposed dosing regimen

17. Additional Facts… • PI institution becomes site for their trial if not network site • Budget for PI and their site • PI becoming part of NEC and publication/data sharing committee for duration of their study • External statistician possible as consultant • Needs justification

18. What CCC and DCC Contribute to the Protocol Workflow Christopher Coffey, PhDPrincipal Investigator, NeuroNEXT Data Coordination Center (DCC)

19. CCC Work with Protocol PI / Sponsor on protocol and budget development Determine NeuroNEXT site interest / feasibility to conduct study Work with Protocol PI / Sponsor on regulatory submission (IND), as needed Identify third party vendors, as needed DCC Work with Protocol PI/Sponsor on study design Statistics Design Team available to provide statistical input to potential network project applicants Early discussions will also involve Team Leaders from Data Management, IT/Development, and IBI in order to discuss any protocol-specific needs or tasks that might require specialized methods Protocol Workflow: Conceptual Phase

20. CCC Initiate Study Team meetings Develop study timelines Facilitate third party vendor contract process Develop ICF and other study documents cIRB submission and review of protocol and study related documents Collaborate with DCC to finalize CRFs DCC Develop a Scope of Work Document Develop a Data Management Plan Develop a Monitoring Plan Develop a Quality Management Plan Finalize CRF’s for each protocol Create written user specifications for website, data entry, and other database features Protocol Workflow: Planning Phase

21. CCC Plan and conduct Study Orientation meeting Collect, review and maintain regulatory documentation Track and ensure site staff have met all requirements prior to “activation” Track metrics for study start up Assist Protocol PI / Sponsor to post trial on clinicaltrials.gov DCC Provide initial training to PI and coordinators at each participating site Develop an Internet User’s Guide and Data Entry Certification Manual Develop a regulatory database that will allow CCC to upload all site regulatory files – which will aid in the monitoring process Protocol Workflow: Protocol Implementation Phase

22. CCC Provide overall support for Network sites Assist with protocol related questions Submit amendments to cIRB Manage key study events; SAEs, deviations, dosage adjustments, etc. Work with DCC Study Monitors to manage protocol and GCP compliance issues Track metrics for site performance DCC Maintain web-based data entry system Track and clarify data queries Track timeliness of data entry Conduct site monitoring visits Produce protocol-specific reports for review during life of project Assist with any additional required training Protocol Workflow: Protocol Maintenance Phase

23. CCC Work closely with NeuroNEXT sites, Protocol PI / Sponsors, DCC, and NINDS to ensure efficiency of close-out activities including query resolution DCC Conduct site close-out visits Resolve any final data queries Work closely with protocol investigators, CCC, and NINDS to ensure close-out activities take place quickly so that a final “locked” dataset can be made available for the primary analysis Protocol Workflow: Protocol Close-Out Phase

24. CCC DCC After final data lock, Statistics Implementation Team will perform final data analysis Team will work on programs while trial is underway Goal is to have a seamless transition from data lock to data analysis – in order to provide near immediate results once data lock has occurred Protocol Workflow: Analysis Phase

25. CCC Assist Protocol PI / Sponsors, DCC, and NINDS with preparation of abstracts, manuscripts and or clinical trial reports Assist Protocol PI /Sponsors with posting results on clinicaltrials.gov within 12 months of database lock DCC Present key findings at appropriate scientific meetings Publish results in peer-reviewed journals Data sets will be shared with other interested parties Protocol Workflow: Dissemination Phase

26. NeuroNEXT Contacts • NINDS • Elizabeth McNeil, MD, MSc mcneilde@ninds.nih.gov • Clinical Coordinating Center • Merit Cudkowicz, MD, MSc mcudkowicz@partners.org • Data Coordinating Center • Chris Coffey, PhD christopher-coffey@uiowa.edu

27. We Will Now Take Questions • Use the raise hand function to ask a question • Once called on your line will be un-muted • If the audio function fails for whatever reason you may type your question into the chat box • www.ninds.nih.gov/NeuroNEXT • To obtain a copy of this slide deck please contact: jobrien22@partners.org