1. ?? Collaborations for hypothermia research ?? Target disorder Different technologies Treatment protocols Basic/translational/clinical

2. The NIH Roadmap: Four themes emerged Revolutionary Methods of Research New Pathways to Discovery Multi-disciplinary Research Teams of the Future Re-engineering the Clinical Research Enterprise

3. Collaborations Why do it? Why do it? Sum of the parts…. What NIH does: Disease specific (SPORs, SCORs, etc.) Investigator-initiated: P50, P01 Clinical trials “networks” Large clinical trials

4. Bioengineering Research Partnerships PAR-03-032 expires August 23, 2003 Trans-NIH Technology plus biological system Hypothermia: Lance Becker, NHLBI

5. National Institute of General Medical Sciences www.nigms.gov Integrative and collaborative approaches to research Must involve investigators at different institutions and must introduce new collaborative and interactive activities $300,000 GLUE grants Much larger Not available in 2003; ???? 2004

6. Specialized Program of Translational Research in Acute Stroke PAS-01-092P50 mechanism Establish a network of centers: 3 centers now Collaboration between EMS, ED, Neurology, Radiology Phase I trial of endovascular hypothermia w/wo tPA (Patrick Lyden at UCSD)

7. NINDS Initiative in Translational Research NINDS Cooperative Program in Translational Research (PAR-02-139)(PAR-02-139) NINDS Institutional Center Core Grants to Support Neuroscience Research (PAR-02-059) (PAR-02-059)

8. NINDS Cooperative Program Translational Research Conferences (U13) Single-Component Translational Research Projects (U01) Multi-Component Translational Research Projects (U54)  5 years; negotiate budget$; milestones; involve NINDS program directors

9. Clinical trials are collaborations Field Administration of Stroke Treatment - Magnesium (FAST-MAG) Trial: A Randomized, Double-Blind, Placebo Controlled Trial of Neuroprotective Magnesium Sulfate Therapy for Acute Stroke Administered Within 2 Hours of Onset by Paramedics in the Field UCLA Stroke Center; USC Department of Emergency Medicine; Los Angeles County Fire Department Paramedic System; Los Angeles City Fire Department Paramedic System R01, 1 PI

10. Priorities for Clinical Collaboration Follow a good pre-clinical lead Timing/duration of target mechanism Timing/duration of intervention Mechanism exists in human disease Outcome measures show an effect Patients available

11. Trials in Consortia Phase I/II and NINDS Pilot trials Fixed sample size Staged designs Selection trials NOT underpowered Phase III Phase III: Outcomes clinically meaningful Types of trials

12. Brain injury Mechanisms complex and interrelated Timing may be unique Injuries heterogenous Individual differences among patients Multiple therapies or staged therapy

13. Conferences to assess a field Expert recommendations often include formation of groups to tackle specific problems or development of guidelines. NHLBI workshops PULSE (post-resuscitation & initial utility in life saving efforts) Neurocognitive outcome after CABG Working group on trauma research NINDS Clinical trials in brain injury

14. Consensus needed? Methods of hypothermia Intervention parameters Disorders to be treated: Patient characteristics ? Preventing hyperthermia Additional therapies Comparability among trials

15. Collaborations Advantages Results quicker Compare results Educate investigators Raise standard of care or state-of-the-art Do the BIG experiment Disadvantages Expense Logistics Personnel intensive Locked-in syndrome Who’s in charge? Flexibility limited

16. con·sen·sus : opinion/position reached by a group as a whole or by majority will. General agreement or accord con·sor·ti·um : association or combination…for the purpose of engaging in a joint venture. A cooperative arrangement among groups or institutions col·lab·o·rate: to work together, especially in a joint intellectual effort