The TRACK TBI study: Common Data Elements and Comparative Effectiveness

in the Era of “Big Data”

AC Duhaime, M.D.

Director, Pediatric Neurosurgery, Massachusetts General Hospital

Professor, Neurosurgery, Harvard Medical School

Important Requirement for New Clinical Studies: Acronyms

• TRACK TBI – Transforming Research and Clinical Knowledge in Traumatic Brain Injury

• ADAPT - Approaches and Decisions for Acute Pediatric TBI

Disclosure: Salary support from NINDS for this study

What this talk will cover

• What’s behind the trend toward studies of this design in head trauma?

• Is it likely that anything will come of this type of study?

• Will these studies affect my life?• Are there PM&R network and research

opportunities in this study paradigm?

Conceptual semantics

• Head injury; head trauma• Traumatic brain injury (TBI)• The concussion “spectrum”

TBI umbrella

Parenchymal brain injury

Skull injuryExtra-axial hemorrhage Transient, “non-visible” or

“non-structural” dysfunction

Terminology and Classification of Head Injuries

• By type (radiology)– “Where and what” – “epidural hematoma”– Pathophysiologic descriptors – e.g. “brain

swelling”

• By severity– Glasgow Coma Scale (GCS)

• “Mild/minor, moderate, severe” – Moving away from this

• By mechanism– Forces involved – impact, inertial, blast

Neuroprotectants tested in human TBI trials

• Steroids – negative or worse• “Lazaroids” (21 aminosteroids) – negative• Ca+ channel blockers – negative x 3• Glutamate antagonists (selfotel, aptiganel,

eliprodil, licostinel gavestinel) – negative• Hypothermia – negative or worse (adults and

children [stopped for futility] )

• Progesterone – stopped for futility (ProTECT)

Limitations in past clinical HI trials

• Most had inclusion based on initial GCS– Usually “GCS <=8” – Mixed together many types of injuries and

patients

• Outcomes general, dichotomized

ALL trials failed

Limitations in past clinical HI trials

• Most had inclusion based on “severity”– Usually “GCS <=8” – Mixed together many types of injuries and

patients

• Outcomes general, dichotomized

ALL trials failed

Limitations in past clinical HI trials

• Most had inclusion based on “severity”– Usually “GCS <=8” – Mixed together many types of injuries and

patients

• Outcomes general, dichotomized

ALL trials failed

Halo effect – control AND treatment groups showed improved outcomes

due to standardization of care

“Guidelines” and “linear algorithms”

Many adapted from clinical trials protocols

NIH 2008 – match treatment to pathophysiology

Geoff Manley MD

Trends in head injury management:from “severity-based” to “pathoanatomic-

based” treatments

Categorization

MGH initial triage/management protocol

**Unoperated epidural, significant contusion, others at discretion of treating physician

So how DO you figure out what works best, for which patients,

at which time?

• And how do you test NEW treatments?

Three simultaneous trends have driven current TBI research model evolution

• NINDS Common Data Elements• Comparative Effectiveness Research

• Advances in informatics

Multidimensional data for better patient/injury characterization

• Clinical data• Imaging data• Treatment info

– Acute

–Rehab• Biomarker data• Comprehensive outcome data

Common Data Elements (CDE’s)

• ALS• Muscular dystrophy• Epilepsy• Friedrich’s ataxia• Headache• Huntington’s disease• Multiple sclerosis

• Myesthenia gravis• Neuromuscular diseases• Parkinson’s disease• Spinal muscular atrophy• Stroke• Traumatic brain injury

“The purpose of the CDE Project is to standardize the collection of investigational data in order to facilitate comparison of results across studies and more effectively aggregate information into significant metadata results. The goal of the National Institute of Neurological Disorders and Stroke (NINDS) CDE Project specifically is to develop data standards for clinical research within the neurological community. Central to this project is the creation of common definitions and data sets so that information (data) is consistently captured and recorded across studies.”

Design better outcome measures• Dichotomized Glasgow Outcome Scale

too crude– Insensitive to small effects

• Need “ecologic validity” – Should reflect how function is affected in the

real world

Lots of data for cognitive, psychological outcomes, less for specific motor function

“Observational” study• You can treat patients however you want• Have to collect data, biospecimens,

imaging, and outcomes per strict protocol• Data sharing agreement• Premise: by pooling data, may be able to

interrogate data to answer many questions

CDE process

• Version 1.0 – Work groups– Manuscripts (2010)

• Version 2.0 – Wider input; “core, basic,

supplementary”– Website

• commondataelements.ninds.nih.gov

How do you describe and quantify rehab interventions?

So, you’ve got a “list” of “CDE’s” – now what?

Informatics

TranSMART

}answers

CDE beta testing

• TRACK TBI pilot (2010-11)– 4 sites, 650 patients, 11 months

• Clinical data, blood specimens, MRI’s• Detailed outcomes• Federal Interagency TBI Research (FITBIR) data

repository

– First test of comparative effectiveness strategy

TRACK TBI Pilot sample findings

• In pts with normal CT, 30% had MRI abnormalities which predicted worse outcome at 3 months

• Glial proteomic marker correlated with CT findings• PTSD vs. cognitive dysfunction separable by

appropriate outcomes tools• Pts with milder injuries had similar outcomes at 6 mo

whether observed in ED or admitted to ICU or floor

No rehab questions yet!

Where we are now: TRACK TBI

• 11 centers; multi-site UO1 – Two also pediatric

• 3000 patients over 4 years (~1500 to date)– Clinical data, biomarkers (n=89), genomics, MRI’s

• FITBIR and central repositories

– F/u 3, 6, 12 mo

• Inclusion: – Present with TBI and enrolled within 24 hours– Have imaging

Some specific CER aims• Effect of platelet drugs and transfusions

on outcome • Predictors of low risk of deterioration

allowing lower level of observation– Economic analysis

• Many others proposed and possible– Role of early MRI in TBI in kids

–Who needs what rehab?

Conclusions

• Large-scale, data-base oriented TBI studies are the current trend– Infrastructure now developed– Promising but time will tell

• Common Data Elements in research – Will become standard– Many opportunities for rehab-based specialties

Thank you