Traumatic Brain Injury collaboration
Global collaboration to combat Traumatic Brain Injury
Traumatic Brain Injury, usually abbreviated TBI, is a leading cause of death and disability around the world, with an expected 50-60 million new cases annually. The majority of incidents occur in low and middle income countries, with traffic accidents being one of the most frequent causes, but TBI is common everywhere - you have an almost 1 in 2 chance to suffer a TBI in your lifetime. Disabilities related to TBI are challenging to treat and to rehabilitate, and therefore place a huge economic burden on society; an estimated 400 billion USD per year.
Though support for neurotrauma research has increased over the last few years, it is nowhere near the funding for other neurological diseases such as Alzheimer’s. New solutions are needed across the range of TBI areas, in prevention as well as in clinical care and research. For this we need better diagnosis methods, improved classification and prognostic models, and more evidence-based guidelines for treatment. This would make it easier for researchers and medical staff to specify and monitor each patient’s specific stage and type of disease. But such improvements depend on addressing the current issues of inadequate data, varied data quality, integrating different types of data, and lack of agreed guidelines for standard reporting.
These global challenges of TBI require equally global collaboration and a change in research culture to endorse data sharing more widely. The need for sustainable multi-disciplinary and international approaches led to the establishment of International Initiative for Traumatic Brain Injury Research (InTBIR), a collaboration between the European Commission, the US NIH-NINDS, the US Department of Defense, the non-profit One Mind, and the Canadian Institute of Health Research. InTBIR studies, planned for 2013-2020, will include over 40000 patients and will result in improved care both on the population and individual level. Curated biorepositories and databases from the studies will provide a legacy for future research, and all projects will comply with standards based on the Common Data Elements, which allows data collection, analysis and sharing across the research community.
INCF's work in TBI involves development of a data/informatics platform, internationalization of the Common Data Elements, and facilitation of novel analytical methods. Most of this work is performed within the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury project, funded by the European Commission and led by Prof. Andrew Maas, University of Antwerp, and Prof. David Menon, University of Cambridge.
Started in 2013, CENTER-TBI aims to better characterize TBI and identify the most effective clinical interventions, link patient profiles with effectiveness of treatments (toward “precision medicine”), and improve outcomes via comparative-effectiveness studies. The project has collected an unprecedented scale of data from 65 participating centers across 20 European countries, with data about 5400 patients being collected in the core study and 22760 in the Registry. Patients were stratified into three layers of severity: people doing well enough to be released from the emergency room, those admitted to a ward and those admitted to intensive care. For each patient, there were several thousand individual clinical, treatment and outcome variables, many with multiple recordings over time. Due to standardized data collection protocols and CDEs, data from beyond Europe has been integrated with the Center-TBI European data: data from 214 patients in India and 200 patients in Australia is included. Thanks to the standard protocols, the data hosted in Europe is able to be compared with data from the large-scale US study Track-TBI.
Bringing all these different kinds of data together and making them manageable for regular researchers required development of new scalable data management systems and search tools. This work has been led by INCF, and resulted in the development of the INCF Neuroinformatics Data Collection Platform (NDCP), a data management service for studies about the diseases and injuries related to the brain.
“Our job has been making simplicity out of complexity; it's taken some years, but anyone who can use a computer should, with a little training, now be able to use the database” says Visakh Muraleedharan, software programmer at INCF.
The NDCP can be used for managing a wide range of data types, such as clinical data, high resolution ICU data, imaging data, cognition test reports and biomarker/genomics data. The data is integrated from different data sources and data management systems, curated, annotated and associated with individual patients using a Global Unique Personal Identification number. The platform also has robust interfaces to download subsets of data in various formats, provided by a data access tool called Neurobot which is developed by INCF, and can integrate with different existing data analysis platforms.
The main infrastructure for CENTER-TBI data collection is located at PDC Centre for High Performance Computing in Stockholm. One of the servers is dedicated for hosting the(e-CRF) web-based application for collection of data from various centres. The second server is used to stage data related to clinical, neuroimaging, ICU, lab sampling and cognition tests, and to host data from India and China. Based on the role and access privileges given, participating sites can access various reports from the e-CRF itself.
INCF has developed a tool, Neurobot, to access the data. Using this and the clinical knowledge management platform TranSMART, researchers can access and analysz the project’s data. Large data files, like CT/MRI scans and ICU data, are accessible through a cloud service using an URL downloaded from the database. There are also APIs for connecting to and accessing the database with external applications. Access rights for the users are controlled through the LDAP server controlled by the project coordinating site at University of Antwerp.
The harmonized data collection pioneered within CENTER-TBI allows for meta-analyses across studies; for the first time, data collection in TBI is globally harmonized and coordinated. But it will not be the last - future InTBIR studies will use the same framework to build and extend on the CENTER-TBI results. This leads to great potential for global breakthroughs in the treatment of this disease, and improved lives for the millions of people affected.
The Lancet Neurology’s Commission on TBI (Nov 6, 2017)
Commentary in Lancet Neurology: The CENTER-TBI core study: The making-of (Nov 6, 2017)
Forbes commentary on the Lancet Neurology Commission (Nov 9, 2017)