The International Initiative for Traumatic Brain Injury
Research (InTBIR)

InTBIR is a global effort to coordinate and harmonise clinical research activities across the full spectrum of TBI injuries with the long-term goal of improving outcomes and lessening the global burden of TBI by 2020.

This will be achieved by pursuing three specific objectives:

• Further establishing and promoting the use of harmonised, international standards for TBI clinical data collection; InTBIR supports the use of the TBI Common Data Elements as standards for data collection;
• Creating a TBI patient registry by building common databases and linking them through an accessible, user-friendly interface for both entry and data search;
• Developing and applying sophisticated analytical tools to enable Comparative Effectiveness Research (CER) for TBI and identify best practices in early diagnosis and treatment.

An international collaborative effort towards data collection and sharing will facilitate:

• Development and validation of surrogate markers of injury and recovery;
• Development and validation of a patho-anatomical and biomarker-based patient classification system to enable targeted therapies;
• Application of CER to determine the benefits of current and new treatments;
• Prediction of outcome and of its modulation by patient, injury, and the quality of general and specific management across the continuum of care.

TBI is the most important cause of disability in individuals under the age of 45. The annual incidence of TBI is estimated at up to 500/100,000 in North America and Europe and is increasing, due mainly to increased numbers of motor vehicles accidents in low- and middle-income countries. The World Health Organization (WHO) predicts that deaths from road traffic incidents (primarily due to TBI) will double between 2000 and 2020 and TBI will rise to the third leading cause of global mortality and disability by 2020 (WHO, 2009). It occurs more commonly in low socioeconomic populations and is increasing in the elderly, particularly in women, in developed countries. Acute and long-term risk factors associated with youth and sports-concussions are another major concern, and there is increasing evidence that multiple mild TBIs may pre-dispose to early onset dementia, later substance-use disorders and mental illness.

TBI not only has devastating effects on patients and their relatives but results in high socio-economic costs to society. Wittchen et al. estimated that TBI costs amount to Euro 33 billion per year in Europe alone (Wittchen HU et al. (2011). Eur. Neuropsychopharmacol. 21, 655–679).

Given this high socio-economic burden, TBI has become one of the priorities in the national research agendas of many countries.

In Europe, the European Commission (EC) has invested €50 million on research on traumatic brain injury through its 7th Framework Programme for Research (FP7, 2007-2013). Funded research includes both individual and collaborative grants spanning from understanding basic mechanisms of injury to automated patient data collection in the intensive care unit to brain machine interfaces to facilitate reintegration of TBI patients into society.

In the USA, the National Institutes of Health (NIH) supports approximately $80M/year of investigator-initiated research on TBI. In addition, the U.S. Department of Defence has contributed $10M toward the development of an informatics system for TBI research, which will be housed at the NIH. The Federal Interagency TBI Research (FITBIR) Informatics System will provide a common platform and operational support for exchanging data, protocols, and research-related information. Moreover, the architecture of FITBIR supports federation with other data resources.

In Canada the funding of TBI research over the past decade has totalled approximately $42M CAD through the Open Competition funding opportunities supported by the Canadian Institutes of Health Research (CIHR; $26M) and approximately $16M CAD through funding provided by the Ontario Neurotrauma Foundation (ONF). In April 2012 CIHR’s Institute of Neurosciences, Mental Health and Addiction in partnership with ONF hosted the first national invitational workshop on TBI, which was then followed by the announcement of targeted funding opportunities for TBI in Canada (over $9M CAD).

TBI is an important global burden that has until now defied conventional approaches to diagnosis and therapy development because of its heterogeneity and complexity. Randomised clinical trials have had limited success in developing effective TBI treatments that are broadly applicable. It is therefore necessary to explore alternative approaches to therapy development for TBI. CER holds promise that valid answers can be generated if sufficiently large datasets and rigorous statistical methods are used. The correct application of CER however requires a very large, detailed patient registry that is representative of injury and patient variability, the endorsement of common data standards, sophisticated analyses to demonstrate causal relationships between patient-specific factors, treatments, and outcomes, the involvement of a variety of clinical centres across different countries and, last but not least, a sizable economic effort. All this can be better achieved through an international collaborative research effort.

To this end, the EC and the NIH organised workshops in Las Vegas, Washington and Brussels to explore the scientific rationale, added value and feasibility of an international collaboration in the field of TBI.

As a results of the discussions, InTBIR was set up at the Brussels workshop on 19-20 October 2011.

Funding agencies committing to InTBIR included the Institute of Neurosciences, Mental Health and Addiction of the Canadian Institutes of Health Research (CIHR-INMHA), The European Commission Directorate General for Research and Innovation (EC), the National Institute of Neurological Disorders and Stroke (NINDS) and the Center for Information Technology (CIT) of the US National Institutes of Health (NIH), and the US Department of Defence (DoD).

Other agencies and organisations expressed interest in InTBIR activities but were not ready for a formal commitment.

InTBIR is open to all funding agencies wishing to support InTBIR goals as data standardisation and sharing can only benefit from a wide participation.

Funding agencies participating to InTBIR will coordinate research investments while working within their existing frameworks. Projects supported by participating agencies are expected to attend InTBIR meetings, network and collaborate.

Several InTBIR calls and initiatives are expected during the course of 2012:

EC:

• A call for proposals for a Euro 30 million project on TBI clinical data collection is currently included in the FP7 2013 Health work programme.
• The draft topic text is available online (see page 21 of the 2013 Health orientation paper). The final, legally binding text is expected to be published around 9 July 2012 with deadline for proposal submission foreseen for 2nd October 2012.
• Funding is open to applicants based in the EU or associated countries . Applicants from third countries (i.e. non-EU and non-associated countries (1)) are eligible for funding only if their contribution is deemed essential to the project.

Canada:

• In April 2012, the CIHR’s Institute of Neurosciences, Mental Health and Addiction in partnership with the Ontario Neurotrauma Foundation hosted the first national Invitational Workshop on New Opportunities in Traumatic Brain Injury Research.
• The workshop was followed by the announcement of targeted funding opportunities for TBI in Canada (over $9M CAD). Funding is open to researchers/clinicians affiliated with Canadian institutions. More information as well as the call text will be made available here.

USA:

• Version 2.0 of the TBI common data elements (the data standards endorsed by InTBIR) is now available.
• The FITBIR Informatics System is scheduled to launch on July 15, 2012. The Federal Interagency Traumatic Brain Injury Research (FITBIR) informatics system has been developed to share data across the entire TBI research field and to facilitate collaboration between laboratories, as well as interconnectivity with other informatics platforms.
• The NeuroQual (Qual Life Res. 2012 Apr;21(3):475-86), an NINDS sponsored patient reported outcome tool for neurological outcomes, is being validated for TBI.

InTBIR will rely on the cooperation among funders (providing oversight), an international scientific advisory committee (providing scientific advice), working groups and supported research projects. An InTBIR meeting will be organised annually so that all InTBIR stakeholders (funders, advisors and project participants) will have an opportunity to meet and share results.

Participating agencies are currently preparing a document setting InTBIR goals, governance, strategies and rules for participation. It will be made available online on the InTBIR website in 2012.

• Health Research at the European Commission
• The FP7 Health 2013 orientation paper
• FITBIR
• The TBI Common Data Elements
• CIHR-INMHA
• NINDS
• CIT
• US Department of Defence