ADAPT

Australia

CIHR - IRCS

India

CENTER-TBI

InTBIR

Towards Global Collaborations

Andrew MaasDavid Menon

May 28, 2015Arlington, USA

ONE MIND

TRACK-TBI

China

WHAT IS INTBIR?InTBIR : International Initiative for TBI ResearchCollaboration : 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

INTBIR PROJECTS

Approaches and Decisions for Acute Pediatric TBI (ADAPT) Trial

CREACTIVE study on TBI

CIHR studies

Neuroinform

atics and biostatistics platform

e-CRF

QuesgenMike

Jarrett

INCFSean Hill

CENTER-TBI COLLABORATION

44 scientific institutes

76 sites for data collection

22 countries

Ego = 1

Knowledge

‘More the knowledgelesser the ego, lesser the knowledgemore the ego …’

- Albert Einstein

MAKING COLLABORATIONS WORK

TEAM = TEAM

Make everyone feel responsible Facilitate (sub)studies

Con

Increased burden of data collection

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

PARADIGM SHIFTSThe 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

EXAMPLES OF HOW PROTECTIONISM INHIBITS PROGRESS

The IMPACT projectInternational 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

‘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

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

CHALLENGES IN A MULTINATIONAL PROJECT

12Selection 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

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!

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

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

RECRUITMENT STATUS CENTER-TBI

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

Neuroinform

atics and biostatistics platform

e-CRF

QuesgenMike

Jarrett

INCFSean Hill

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.

Provider profilingCharacterising systems and delivery of care in centres

Unadjusted for case mix Adjusted for case mix

IMPACT database (n=9578) 2.4 3.3

IMPACT – US (n=3325) 2.0 2.4

IMPACT – EU (n=5706) 2.4 3.8

A NEW VISION : MAKE USE OF THE EXISTING HETEROGENEITY

• Do not limit heterogeneity

• Comparative Effectiveness

• Multilevel: structure – process – individual

To include the “why” question

CENTER-TBI Registry n=15-25 000

CENTER-TBI Core Study (n=5400)

CENTER-TBI Europe78 sites

Recruitment : 18 monthsAim : 5400 patients

Current enrollment Core Data : 300 Registry : 700

Center-TBI China40 sites

Ready to start

coordinators : Professor Jiang

Dr Gao

Increased output and enhanced efficiency by

International collaboration

Data sharing

Global franchising

NIH

InTBIR

EU

CIHR

China India

Australia New-Zealand

THE CHANGING LANDSCAPE OF TBI RESEARCH

• Broad and generalisable approaches• Comparative effectiveness research • Collaboration and data sharing• Global efforts

WHAT WILL GLOBAL COLLABORATION FURTHER GIVE

• Unique network of collaboration

• Huge knowledge resource

• Make our world smaller – safer – and a better place