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InTBIR meeting: San Francisco June 2014 Development of joint projects

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InTBIR meeting: San Francisco June 2014 Development of joint projects. Areas of Collaboration. Protocol harmonisation: TRACK-TBI/CENTER-TBI; ADAPT/CENTER-TBI; Canadian pediatric CDE project aligned with TRACK-TBI ; & collaborative work between Canadian teams

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InTBIR meeting: San Francisco June 2014

Development of joint projects

areas of collaboration
Areas of Collaboration

Protocol harmonisation:


Canadian pediatric CDE project aligned with TRACK-TBI; & collaborative work between Canadian teams

Coordinated data collection :


Processing and analysis alignment:

Sample processing, outcomes, imaging, genetics

Novel collaborations:

CANTAB-NIH Toolbox cross-comparison, GAIN, EpiBios, ICON


Diaz-Arrastia (USUHS), Hammond (Indiana), McAllister (Indiana), Manley (UCSF), Menon (Cambridge), Richardson (Cambridge) Neale (Broad), Palotie (FIMM/Broad), Rosand (Broad/MGH), Tenovuo (Turku), van Gils (VTT) Wagner (UPMC)

  • Clinical implications of genetic variability uncertain
  • However, only ~30% of outcome variation explained
  • Need larger sample sizes which determine incremental benefit of knowing genetic variability
  • No single large dataset; many moderately sized datasets
  • Methods experts (Palotie, Richardson, Rosand, Neale)
  • Collaborative study may be more than sum of its parts
  • Federated data collection overcomes many barriers
gain solutions
GAIN solutions
  • Initial plans aimed at:
    • Existing datasets and sample banks (~4000 patients)
    • Included TRACK-TBI pilot and TBIcare
    • Candidate gene approach
  • Subsequent discussions
    • Federated analysis (FIMM/Broad Institute) – no sample transfer
    • Move to GWAS + exome enrichment (Ben Neale; Broad Institute)
    • Use available population controls
    • Sample transfer in process, but funds are limiting
  • A basis for shared analysis plans in TRACK-TBI/CENTER-TBI
  • Consent for wider comparisons - other diseases (e.g. PGC)
  • Potential application to Wellcome Trust (initial discussions+)
epilepsy bioinformatics study epibios
Epilepsy Bioinformatics study (EpiBios)
  • PIs: Vespa, Engel, Jensen, Pitkanen, Litt, Toga
  • Epilepsy Bioinformatics Study (EpiBioS):
    • Center without walls Working Group
    • 100 contributors: leading figures in animal and human epilepsy
    • Bioinformatics approach to identify reliable epilepsy biomarkers
  • Goals of the project are to:
    • Determine biomarkers of epileptogenesis
    • Identify patients at highest risk for epilepsy after a brain insult,
    • Study mechanisms of epileptogenesis
    • Stage the epileptogenic process.
  • Funding:
    • P20 grant support at present (1P20NS080181-01)
    • UO1 application Fall 2014
rationale for collaboration
Rationale for Collaboration
  • TBI major acute brain insult leading to epilepsy
    • Attributable risk from TBI ~15% of all epilepsy
  • TBI - excellent clinical model for epileptogenesis
    • Temporally defined insult, tracking of patients feasible
    • Informatics approach feasible
  • Existing resources in place
    • Database structure (LONI-USC)
    • Preliminary feasibility and risk factor data (UCLA; NNTS Poster A1-15)
    • Current EEG collaborations several centres, Moberg, iEEGcentre (UPenn)
  • Economic benefits of collaborative research and increased scale
    • Enhanced data collection in InTBIR study sites (n)
    • TRACK-TBI (5), CENTER-TBI (3), ADAPT(3) leads positive
    • Additional funding allows enhanced use of data already being collected to address an important question
proposed strategy for epibios
Proposed strategy for EpiBioS
  • Incidence and determinants of PTE in large clinical cohort: TRACK-TBI, CENTER-TBI, ADAPT (n=5000/2 years)
  • High temporal resolution cEEG data from severe TBI (n=900/2 yrs)
  • Animal study to develop valid biomarkers for PTE
  • Translational study: PTE > other acquired epilepsy
  • New UO1 & supplementary funding to parent studies for:
    • Primary epilepsy-related data collection
    • Biomarker analysis, EEG analysis, imaging analysis
    • The informatics process
    • Network functions and workshops
  • The NINDS special program in Epileptogensis as UO1 mechanism
specifics of the collaboration
Specifics of the collaboration
  • Data sharing of all primary data for informatics analysis to determine risk factors/ consequences of PTE
  • Harmonization of MRI protocols to meet PTE hypotheses
  • Add cEEG and blood biomarkers for PTE in the subgroup of severe TBI (ICU cohort) high temporal resolution study
  • Add telephone follow up for epilepsy at 1 and 2 years after TBI
  • Add blood biomarker assays at serial times points to detect PTE biomarkers (2 wks, 3 mo, 6 mo, 12 mo)
  • Add confirmatory assessment on subset of patients screening positive by telephone for PTE (EEG, clinic visit) at 1 or 2 years




international collaboration on neuroinflammation in tbi
Investigation of neuroinflammation in TBI

Temporal pattern and outcome impact

Experimental-human comparisons; biology – innate/adaptive; M1/M2

Four groups + industrial partner (GSK)

Cambridge (Menon, Hutchinson, Coles)

Calgary (Barlow, Gallagher,

Milan (Zanier)

Glasgow (Stewart, McMillan)

Four clinical cohorts

Paediatric mTBI (Calgary)

Adult Mod/severe TBI (Cambridge)

Repeated mTBI (Rugby- Glasgow)

Neuropathology archive (Glasgow)

Two experimental models

Mild TBI (Calgary)

Mod/Severe TBI & microglial biology (Milan)

International Collaboration On Neuroinflammation in TBI
  • Outline application
  • Science rated well
  • Not shortlisted
  • “limited evidence of collaboration between partners”
  • Combined pilot data collection - resubmit
lessons learned
Lessons learned
  • InTBIR is more than the sum of its parts
  • Major collaborative opportunities
  • Many potential strategies – depends on goal
  • Advantage in clinical studies self-evident, but success in funding remains unproven
  • Translational approaches may hold substantial potential, but need nurturing/maturing