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CENTER-TBI has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n°602150 InTBIR meeting: San.

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Presentation on theme: "CENTER-TBI has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n°602150 InTBIR meeting: San."— Presentation transcript:

1 CENTER-TBI has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n°602150 InTBIR meeting: San Francisco June 2014 Development of joint projects

2 AREAS OF COLLABORATION 2 Protocol harmonisation: TRACK-TBI/CENTER-TBI; ADAPT/CENTER-TBI; Canadian pediatric CDE project aligned with TRACK-TBI; & collaborative work between Canadian teams Coordinated data collection : TRACK-TBI/CENTER-TBI; CENTER-TBI/CREACTIVE Processing and analysis alignment: Sample processing, outcomes, imaging, genetics Novel collaborations: CANTAB-NIH Toolbox cross-comparison, GAIN, EpiBios, ICON

3 3 5 additional CANTAB platforms for use in US sites for cross-validation

4 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 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)

5 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+)

6 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

7 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, iEEG centre (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

8 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

9 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

10 CD3/43 MBP Merge

11 11 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 ICON-TBI ERANET-NEURON grant Outline application Science rated well Not shortlisted o “limited evidence of collaboration between partners” o Combined pilot data collection - resubmit

12 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


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