1. ADAPT Australia CIHR - IRCS India CENTER-TBI InTBI R Towards Global Collaborations Andrew Maas David Menon May 28, 2015 Arlington, USA ONE MIND TRACK-TBI China

2. WHAT IS INTBIR? InTBIR : International Initiative for TBI Research Collaboration : European commission – NIH/NINDS – CIHR INTBIR IS MORE THAN THE SUM OF ITS PARTS  The logic of common data platforms (CDEs)  The opportunities provided by Rx variations (CER)  The public benefit of open access to curated data  A global research team with unlimited resources  The strength of numbers  Making impossible questions answerable  New research paradigms (incremental phenotype)  Data driven approaches (INCF)  The power of networks  Accelerating knowledge transfer to patient care  A paradigm shift in research collaborations

3. INTBIR PROJECTS  Approaches and Decisions for Acute Pediatric TBI (ADAPT) Trial  CREACTIVE study on TBI  CIHR studies

4. Neuroinformatics and biostatistics platform e-CRF Quesgen Mike Jarrett INCF Sean Hill

5. CENTER-TBI COLLABORATION  44 scientific institutes  76 sites for data collection  22 countries Ego = 1 Knowledge ‘More the knowledge lesser the ego, lesser the knowledge more the ego …’ - Albert Einstein

6. MAKING COLLABORATIONS WORK TEAM = TEAM  Make everyone feel responsible  Facilitate (sub)studies Con  Increased burden of data collection

7. DATA SHARING: TENSIONS Data sharing ↔ current system of academic credits Funding agencies  Strong pressure to grant early access to other investigators  Motivation : accelerate TBI research; optimal use of public funding Investigators “protectionistic” attitude  Motivation : safeguard own work and credits Data sharing = collaboration

8. PARADIGM SHIFTS The past :  Clinical trials: isolate out 1 single factor for treatment  Protectionistic approaches The present :  Broader generalizable approaches  Sharing and collaboration PARADIGM SHIFTS ARE ONLY SUSTAINABLE IF…  Culture changes  System of academic credits changes

9. EXAMPLES OF HOW PROTECTIONISM INHIBITS PROGRESS The IMPACT project International Mission for Prognosis and Analysis of Clinical Trials in TBI  NIH funded 2003-2013  > 60 publications  Prognosis : Robust prognostic models  Trial design and analysis : Increase power by 50%  Common Data Elements : Standardization

10. ‘this letter serves as IMPACT’s demand that Antwerp and/or Erasmus immediately cease and desist from any and all use of the IMPACT Word Mark and the ImPACT mark or any other designations confusingly similar thereto in connection with neurocognitive evaluation products or related goods or services…’ ATTACK ON IMPACT

11. EXAMPLE OF PROTECTIONISM INHIBITS PROGRESS ‘OWNERSHIP OF OUTCOME INSTRUMENTS’ Two of the proposed outcome instruments licensed by Pearson inc. BSI and WAIS-IV subtests. Problem:  Require translation and linguistic validation into multiple languages. Company demands  Pay license fee  Provide all translations to company  Transfer all intellectual property rights on translations to company NO GO

12. CHALLENGES IN A MULTINATIONAL PROJECT 12 Selection based upon Common Data Elements recommendations from Wilde et al. Arch. Phys. Med. Rehabil. 91.11 (2010): 1650-1660, expert discussion, comparability with TRACK-TBI Outcomes for CENTER-TBI. Translations of outcome instruments

13. CHALLENGES IN A MULTINATIONAL PROJECT STANDARDIZATION OF MR IMAGES 3 vendors : GE, Philips, Siemens Per vendor multiple scanner types Per vendor/scanner combination multiple software versions Software versions are not backwards compatible (even within sub-version e.g. protocol from 4.5.6 can’t be used on 4.5.5.) Outdated software (licenses are very expensive) Software licenses -> license for DTI, fMRI, BOLD sometimes not present (expensive) Coils -> 8, 12, 20, 32, 64 channels 31 sites, 31 different set-ups!

14. CHALLENGES IN A MULTINATIONAL PROJECT STANDARDIZATION OF MR IMAGES Example: Siemens Scanner types: 3 Software versions: 6 Coil types: 4 Number of channels: 5 different 3x6x4x5 = 360 possibilities (actually this is not true, because a scanner has a limited number of configurations) 12 scanners, only 2 with the same configuration

15. CHALLENGES IN A MULTINATIONAL PROJECT STANDARDIZATION OF MR IMAGES 3T only coils “black box” implementations of MRI sequences available staff (MR physicist, MR Tech, neuroradiologist) software versions time & willingness to test COMMUNICATION

16. RECRUITMENT STATUS CENTER-TBI

17. Essential components of CENTER-TBI 17 Provider profiling : finger print of center characteristics, in terms of organization, structure, protocol, process. Standardized data collection. Complete outcome assessments. CENTER-TBI : AN INTEGRAL PICTURE

18. Neuroinformatics and biostatistics platform e-CRF Quesgen Mike Jarrett INCF Sean Hill

19. THE POTENTIAL OF IMPROVED CHARACTERIZATION National Research Council (US) Committee on A Framework for Developing a New Taxonomy of Disease. Toward Precision Medicine. Washington (DC): National Academies Press (US); 2011.

20. Provider profiling Characterising systems and delivery of care in centres

21. Unadjusted for case mix Adjusted for case mix IMPACT database (n=9578)2.43.3 IMPACT – US (n=3325)2.02.4 IMPACT – EU (n=5706)2.43.8 A NEW VISION : MAKE USE OF THE EXISTING HETEROGENEITY Do not limit heterogeneity Comparative Effectiveness Multilevel: structure – process – individual To include the “why” question

22. CENTER-TBI Registry n=15-25 000 CENTER-TBI Core Study (n=5400) CENTER-TBI Europe 78 sites Recruitment : 18 months Aim : 5400 patients Current enrollment  Core Data : 300  Registry : 700 Center-TBI China 40 sites Ready to start coordinators :  Professor Jiang  Dr Gao

24. Increased output and enhanced efficiency by  International collaboration  Data sharing  Global franchising NIH InTBIR EU CIHR China India Australia New- Zealand

26. THE CHANGING LANDSCAPE OF TBI RESEARCH Broad and generalisable approaches Comparative effectiveness research Collaboration and data sharing Global efforts

27. WHAT WILL GLOBAL COLLABORATION FURTHER GIVE Unique network of collaboration Huge knowledge resource Make our world smaller – safer – and a better place