CENTER-TBI: Collaborative European NeuroTrauma Effectiveness Research in TBI

Traumatic Brain Injury Clinical Trial

— CENTER-TBI  

Official title:

Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02210221
• Other study ID #: 602150
• Status: Completed
• Start date: December 19, 2014
• Est. completion date: March 31, 2021

Study information

• Verified date: April 2022
• Source: University Hospital, Antwerp
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The research aims of the CENTER-TBI study are to: 1. better characterize Traumatic Brain Injury (TBI) as a disease and describe it in a European context, and 2. identify the most effective clinical interventions for managing TBI. Specific aims 1. To collect high quality clinical and epidemiological data with repositories for neuro-imaging, DNA, and serum from patients with TBI. 2. To refine and improve outcome assessment and develop health utility indices for TBI. 3. To develop multidimensional approaches to characterisation and prediction of TBI. 4. To define patient profiles which predict efficacy of specific interventions ("Precision Medicine"). 5. To develop performance indicators for quality assurance and quality improvement in TBI care. 6. To validate the common data elements (CDEs) for broader use in international settings, and to develop a user-friendly web based data entry instrument and case report form builder. 7. To develop an open database compatible with Federal Interagency Traumatic Brain Injury Research (FITBIR). 8. To intensify networking activities and international collaborations in TBI. 9. To disseminate study results and management recommendations for TBI to health care professionals, policy makers and consumers, aiming to improve health care for TBI at individual and population levels. 10. To develop a "knowledge commons" for TBI, integrating CENTER-TBI outputs into systematic reviews.

Description:

• Introduction: CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) (www.center-tbi.eu) is a project embedded within the International Initiative on TBI Research (InTBIR) (http://intbir.nih.gov/), as a collaboration between the European Commission (EC), the US National Institute of Neurological Disorders and Stroke (NIH-NINDS) and the Canadian Institute of Health Research (CIHR). - Research aims: The basic concept of this project is to exploit the existing heterogeneity in biology, care and outcome of TBI patients to discover underlying pathophysiology, to refine characterisation, and to identify effective clinical interventions. The key driver of our research plan is to collect data from a large number of European centres and sufficiently large cohort to enable 'Comparative effectiveness research' (CER) analyses of differences in clinical care and management pathways in TBI. Improved disease characterization will aid Precision Medicine, a concept recently enunciated by the US National Academy of Science. Such improved characterization and stratification will allow for more targeted therapies. Further, CER provides a promising framework to identify best practices and improve outcome after TBI. CER is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. The purpose of CER is to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at both the individual and population levels. - Cohort: A large core cohort of patients across the severity spectrum in TBI will be recruited at approximately 77 sites in Europe and Israel (the CENTER-TBI Core Study): 5400 patients differentiated into 3 equal strata of approximately 1800: - ER stratum: patients seen and discharged from the ER; - Admission stratum: patients admitted to the hospital but not to the ICU; - ICU stratum: patients admitted directly to the ICU. Balance in numbers between the strata will be aimed for, but sites will be allowed to arrange recruitment strategies to best suit their local requirements. The core cohort will be underpinned by comparison with a larger registry (the CENTER-TBI registry) based on pragmatic data collection of all patients with TBI seen in participating centres (to establish the internal generalizability of our study), and by comparison with national trauma registries (to establish the external generalizability of our findings). In the core cohort, detailed data will be collected on clinical parameters, neuroimaging studies, biomarker analyses, DNA analyses, and longitudinal outcome assessments. In selected centres, extended studies will additionally focus on advanced magnetic resonance (MR) imaging, detailed coagulation profiling and high resolution ICU monitoring. - Sample size assessment: The sample size estimate (n=5400) was based on: - Practical logistic considerations - Power calculations for the different strata, targeting comparative effectiveness analyses, assuming a between-centre and between-country heterogeneity as identified in previous research (expressed by variance parameter from a random effects model, Tau^2 of 0.431) - Postulated odds ratios for intervention effects of approximately 5% improvement in outcome. Overall, these calculations provided a statistical power to detect odds ratios of ~1.2 associated with differences in process or intervention variables across the core dataset with a power of 80%; and require somewhat larger odds ratios in each of the three individual strata. In the registry we expect to be able to detect differences (predominantly in organizational or system variables) with an odds ratio of 1.2 with a power of 82%. - Quality control and assurance: Continuous monitoring of enrolment and completeness of data will be performed by ICON as contract research organization (CRO). Source data verification (SDV) will be performed in 10% of subjects by the CRO. The quality of data collection will be further enhanced by implementing automated data entry checks for impossible/implausible values and implementing data checks for consistency between variables. A task force of study personnel will evaluate the completeness, consistency and validity of submitted data and function as support desk for participating sites. - Data management: Prior to upload to the study database, all acquired data will be stored locally. All patients will be allocated a random Global Unique Personal Identification number (GUPI) which will be linked locally to hospital identifiers. All uploaded data will be de-identified and images will be defaced prior to upload. While blood samples and clinical data will be linked, both sets of data will be kept confidential and anonymised beyond the initial stage of correlation for analysis. All imaging and electronic data will be kept on individually password protected servers. All clinical data will be entered into electronic Case Report Forms (eCRFs) and managed by the 'QuesGen data management platform' (http://www.quesgen.com/) which will be developed in collaboration with Karolinska Institutet International Neuroinformatics Coordinating Faculty (KI-INCF). As data is entered into each form, the system will run data validation checks that include conditionally required data, validation across fields, and validation requirements based on subject type. If any validation check fails, the user is alerted immediately that the data does not meet Quality Assurance (QA) criteria and the issue can be addressed and corrected at that point. All de-identified electronic study data in the CENTER-TBI database will be stored securely in the European data space under supervision of KI-INCF for the duration of subject enrolment and follow-up and for a period afterwards for data analysis and preparation of publications. We estimate that the analysis and publication period will last for several years after the conclusion of subject enrolment. Together with QuesGen Systems, KI-INCF will ensure that data standards are established for the data model e.g. conformity of field formats, field codes and names to ensure consistency across all datasets. Any approved changes will be fully documented with dataset updates to maintain data quality and accuracy. KI-INCF will be responsible for importing cleaned datasets to other analytic platforms as determined by the coordinators. Where applicable, information relevant to the patient's care will be made available to the physician responsible. Data, including blood samples collected as part of this study will be shared in an anonymised form with collaborators from other European states (this is part of a European Commission Framework7 funded program), and with selected collaborators in other countries who form part of an emerging International Traumatic Brain Injury Research initiative. - Computing platform and Neuroinformatics Resource: The KI-INCF will coordinate the establishment of an informatics platform for acquisition, storage and analysis of CDE-based clinical data. The goal is to develop a next generation open standards-based platform to support advanced large-scale analytics and model building. Such a platform also provides a model for future clinical studies on brain diseases and disorders. This development will receive additional support from One Mind for Research. - Statistical analysis plan: Statistical analyses for the Comparative Effectiveness Research (CER) questions will primarily apply random effects modelling, in which center is included at the higher level, and patients are considered clustered within centers. In some analyses, higher levels of clustering will also be considered, e.g. country, or European region; or lower levels, e.g. physicians within hospitals. Confounding factors as measured at the individual patient and/or center level, will be considered extensively, and will be targeted to the specific research question. Statistical analyses for better characterization of TBI will be exploratory, aiming to better understand the complexity of the disease and to discover new associations. In addition to standard statistical descriptive and inferential techniques, we will also employ novel machine learning techniques as appropriate. Prognostic analyses will consider a range of variables, including genetic, demographic and clinical data, physiological signals, imaging results, and biomarkers as predictors of early endpoints and physiologic derangement (e.g. raised ICP), and late outcome, including mortality, functional outcome, quality of life and neuropsychological performance. Previously and newly developed prediction models will be validated by comparison of observed to predicted outcome risks, with predictive performance summarized by measures for model fit, discrimination, and calibration. - Missing data: Every effort will be made to limit the number of missing data in the CENTER-TBI study. Missing values are, however, inherent to any clinical study. Missing values may confound the descriptive, prognostic and CER analyses. Thus, appropriate techniques for dealing with missing values are required. First, we will evaluate the various reasons for missingness per centre. Next, we will explore the use of alternative statistical approaches, including inverse probability weighting and multiple imputation. We will consider missing values in baseline characteristics as well as in short and long term outcomes. Based on simulation studies and practical considerations we will develop standard operating procedures towards the analyses with missing values, respecting the differences in multiple research questions. - Informed Consent: Informed consent procedures will follow local and national requirements in all cases. We anticipate that many potential patients will not be able to consent themselves to participate in this project. The nature of TBI means that some patients may lack capacity to decide to participate in this study especially at the earliest time point. It is important to try and include these patients to ensure that representative samples of patients are included to avoid bias in the study findings. Every step will be taken to ensure that a test of capacity is undertaken before a decision on a person's capacity to consent or not to consent to participation in research is taken. If the subject is not capable of self-consent, all efforts will be made to locate a legally acceptable representative to act on behalf of the subject. When a legally acceptable representative (e.g. consultee/proxy) is identified, their opinion will be sought about the potential participant's wishes and feelings in relation to the project, and whether he or she would have wanted to take part in the study. Subjects are free to withdraw, or be withdrawn by their consultee/proxy if appropriate, at any point in the study, and they need not state a reason. - Impact: The CENTER-TBI project will contribute towards the overall goals of InTBIR, by identifying more effective and efficient treatment provision, thus improving outcome and reducing costs. The science in the project will provide novel information on disease processes, treatment, outcome, and prognosis in TBI, identifying new therapeutic targets and therapies; while the CENTER-TBI repositories will ensure opportunities for legacy research. Thus, the project has the potential to improve current health care and its delivery at both population and individual levels, deliver early scientific advances that could improve the care of patients with TBI, and provide a rich investment for future biomedical research.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4559
• Est. completion date: March 31, 2021
• Est. primary completion date: September 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Clinical diagnosis of TBI
• Clinical indication for CT scan
• Presentation within 24 hours of injury
• Informed consent obtained according to local and national requirements

Exclusion Criteria:

• Severe pre-existing neurological disorder that would confound outcome assessments

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury

Locations

Country	Name	City	State
Austria	Innsbruck Medical University	Innsbruck
Austria	Medical University Vienna	Vienna
Belgium	Antwerp University Hospital	Edegem
Belgium	University Hospitals Leuven	Leuven
Belgium	CHR Citadelle	Liege
Belgium	CHU Liege	Liege
Denmark	Region Hovedstaden Rigshospitalet	Copenhagen
Denmark	Odense University Hospital	Odense
Finland	Helsinki University Central Hospital	Helsinki
Finland	Turku University Hospital	Turku
France	University Hospital of Grenoble	Grenoble
France	Lille University Hospital	Lille
France	University Hospital Nancy	Nancy
France	APHP	Paris
France	CHU Poitiers	Poitiers
Germany	University Hospital Aachen	Aachen
Germany	Charité Campus Virchow	Berlin
Germany	University Hospital Heidelberg	Heidelberg
Germany	Klinikum Ludwigsburg	Ludwigsburg
Hungary	University of Pecs	Pecs
Hungary	University of Szeged	Szeged
Israel	Rambam Medical Center	Haifa
Israel	Hadassah-hebrew University Medical Center	Jerusalem
Italy	Bufalini Hospital	Cesena
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Poloclinico	Milan
Italy	Niguarda Hospital	Milan
Italy	S Raffaele University Hospital	Milan
Italy	ASST di Monza	Monza
Italy	Maggiore Della Carità Hospital	Novara
Italy	Azienda Ospedaliera Università di Padova	Padova
Italy	AOU Città della Salute e della Scienza di Torino	Torino
Latvia	Rezekne Hospital	Rezekne
Latvia	Pauls Stradins Clinical University Hospital	Riga
Latvia	Riga Eastern Clinical University Hospital	Riga
Lithuania	University of Health Sciences	Kaunas
Lithuania	Center of neurovascular surgery, Clinic of neurology and neurosurgery, Vilnius University	Vilnius
Lithuania	Kaunas University of technology and Vilnius University	Vilnius
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Radboud University Medical Center	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Netherlands	Medical Center Haaglanden	The Hague
Netherlands	The HAGA Hospital	The Hague
Netherlands	TweeSteden Ziekenhuis	Tilburg
Norway	Oslo University Hospital	Oslo
Norway	University Hospital Northern Norway	Tromso
Norway	St Olavs Hospital/Norwegian University of science and technology	Trondheim
Romania	Emergency County Hospital Timisoara	Timisoara
Serbia	Clinical centre of Vojvodina	Novi Sad
Spain	Vall d'Hebron University Hospital	Barcelona
Spain	Cruces University Hospital	Bilbao
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Clínico Universitario de Valencia	Valencia
Sweden	Karolinska University Hospital	Stockholm
Sweden	Umea University Hospital	Umea
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Southmead Hospital	Bristol
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Lothian Health Board	Edinburgh
United Kingdom	The Walton centre NHS Foundation Trust	Liverpool
United Kingdom	Kings college London	London
United Kingdom	Salford Royal Hospital	Salford
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield
United Kingdom	University Hospitals Southampton NHS Trust	Southampton

Sponsors (10)

Lead Sponsor	Collaborator
University Hospital, Antwerp	Erasmus Medical Center, GABO:mi, icoMetrix NV, Leuven, Belgium, ICON plc, Karolinska Institutet, San Gerardo Hospital, University of California, San Francisco, University of Cambridge, University of Sheffield

Countries where clinical trial is conducted

Austria,  Belgium,  Denmark,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Latvia,  Lithuania,  Netherlands,  Norway,  Romania,  Serbia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glasgow Outcome Scale - Extended (GOSE) at 6 Months	The Extended Glasgow Outcome Scale is a global scale for functional outcome that rates patient status into 8 categories, going from dead to good recovery.; Death; Vegetative sate; Lower severe disability; Upper severe disability; Lower moderate disability; Upper moderate disability - some disability but can potentially return to some form of employment; Lower good recovery - minor physical or mental defect; Upper good recovery - full recovery; The 6-month GOSE score is available in 3804 patients (84%).	6 months
Primary	SF-12v2 Health Survey (Short-Form Health Survey With 12 Questions) at 6 Months	The SF-12v2 Health Survey uses 12 questions to measure functional health and well-being from the patient's point of view. The SF-12v2 at 6 months is available in 2300 patients.	6 months
Primary	6 Month Quality of Life in Brain Injury (Qolibri-OS) <52 (Impaired)	The Quality of Life in Brain Injury (Qolibri-OS) is a 6 item overall scale that provides a profile of health-related quality of life in domains typicality affected by brain injury, such as physical function, cognition, emotional status, ability to perform daily activities, personal life and social relationship, and satisfaction with current situation and future prospects.; The QOLIBRI scores are reported on a 0-100 scale , where 0=worst possible quality of life and 100=best possible quality of life.	6 months
Secondary	6 Month Post-traumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5) <33 (Impaired)	The PCL-5 is a self-report rating scale intended to assess 20 DSM-5 symptoms of Posttraumatic Stress Disorder. The standard recall period for the PCL-5 is one month. For CENTER-TBI a recall period of one week was used at the 2-3 week assessment, and the standard one month recall period was used at other time points. The sum of scores can range from 0 to 80, where high scores indicate more pronounced PTSD symptoms.	6 months
Secondary	6 Month Rivermead Post Concussion Questionnaire <16 (Impaired)	The Rivermead PCS Questionnaire (RPQ) was originally developed as a measure of severity of symptoms following MTBI. It consists of 16 post-concussion symptoms including headaches, dizziness, nausea/vomiting, noise sensitivity, sleep disturbance, fatigue, irritability, feeling depressed/tearful, feeling frustrated/ impatient, forgetfulness, poor concentration, taking longer to think, blurred vision, light sensitivity, double vision and restlessness. In the original version of the RPQ, participants are asked to rate the degree (on a scale of 0 to 4) to which a particular symptom has been absent or a mild, moderate or severe problem over the previous 7 days compared with premorbid levels. Total scores range from 0 to 64 with higher scores indicating more severe symptoms. Scores equal to or greater than 16 were considered indicative of persisting post-concussion symptoms.	6 months
Secondary	6 Month Galveston Orientation and Amnesia Test (GOAT) < 75 (Impaired)	The GOAT is a standardised assessment used to determine whether a participant is in post-traumatic amnesia (PTA). PTA is an early phase of TBI recovery during which the person with injury shows markedly impaired memory, confusion, fluctuation in performance, disorientation, and other neurobehavioral signs and symptoms. GOAT questions assess orientation, memory for the first event that the participant can recall after the injury, and memory for the last event that the participant can recall from before the injury.; The GOAT's total score must be achieved by subtracting from 100 the total amount of error scores (Total score = 100 - total amount of error scores). Scores lower than 75 point to the fact that the victim is still experiencing amnesia.	6 months
Secondary	6 Month Rey Auditory Verbal Learning Test (RAVLT) - Impaired	The Rey Auditory Verbal Learning Test (RAVLT) is a test of verbal memory that assesses the ability to acquire 15 words. Recall is assessed after each presentation of the list, after the recall of an interference list, and again following a 20-minute delay. The total score for recall of the principal list ranges from 0 to 75, with higher scores indicating better performance.; Impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers.	6 months
Secondary	6 Month Timed up and go Test - Impaired	In the timed up and go (TUG) test, subjects are asked to rise from a standard armchair, walk to a marker 3 m away, turn, walk back, and sit down again, for quantifying functional mobility. The presence of slowness, hesitancy, abnormal trunk or arm movements, staggering or stumbling is used to grade the patient from 1 (normal) to 5 (severely abnormal). Impaired mobility was defined as taking 14 seconds or longer to perform the TUG test.	6 months
Secondary	6 Month JK Coma Recovery Scale - Revised <23 (Impaired)	The Coma Recovery Scale- Revised (CRS-R) is a standardized behavioral assessment instrument designed to measure neurobehavioral function in patients with disorders of consciousness (DOC). The CRS-R is comprised of six subscales addressing auditory, visual, motor, oromotor/verbal, communication and arousal functions. Subscale items are hierarchically-arranged, corresponding to brain stem, subcortical and cortically-mediated functions. Scores range between 0 (deep coma) and 23 (able to follow commands and to use objects purposefully). A total score less than 23 indicates impairment.	6 months
Secondary	6 Month Trail Making Test (TMT) Part A - Impaired	The Trail Making Test (TMT) is a measure of attention, speed, and mental flexibility. Part A requires the individual to draw lines to connect 25 encircled numbers distributed on a page. Part B is similar except the person must alternate between numbers and letters and is more difficult and takes longer to complete. Both sections are timed and the score represents the amount of time required to complete the task, with shorter times indicating better performance. The maximum time allowed is 100 seconds.; Impairment cutoff: > 55.9 (based on the comparison group as a whole and expressed as raw score).; For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).	6 months
Secondary	6 Month Trail Making Test (TMT) Part B - Impaired	The TMT is a measure of attention, speed, and mental flexibility. Part A requires the individual to draw lines to connect 25 encircled numbers distributed on a page. Part B is similar except the person must alternate between numbers and letters, is more difficult, takes longer to complete. Both sections are timed, the score represents the amount of time required to complete the task, with shorter times indicating better performance.; Impairment cutoff: > 143.7 (based on the comparison group as a whole and expressed as raw score).; For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).	6 months
Secondary	6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) PAL (Paired Associate Learning Task) - Impaired	CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For CANTAB PAL, the individual must remember 1 to 8 patterns displayed in different positions on the screen. The score is the number of incorrect responses adjusted if necessary for trials that have not been completed. Scores ranged from 0-194 with lower score indicating better performance.; Impairment cutoff: > 72.3 (based on the comparison group as a whole and expressed as raw score).; For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).	6 months
Secondary	6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) RTI (Reaction Time Task) - Impaired	The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For CANTAB RTI, the individual must respond as quickly as possible to a circle presented at one of 5 positions. The outcome measure is the median time for correct responses (ms).; Impairment cutoff: > 470.9 (based on the comparison group as a whole and expressed as raw score).; For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).	6 months
Secondary	6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) SWM (Spatial Working Memory Task) - Impaired	The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For the CANTAB SWM, the participant searches for tokens in boxes on the screen. The between errors measure is the number of times the participant queries a box that has already been searched. Errors ranged from 0 to 151, with lower numbers indicating better performance.; Impairment cutoff: > 52.0 (based on the comparison group as a whole and expressed as raw score).; For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).	6 months
Secondary	6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) RVP (Rapid Visual Information Processing Task) - Impaired	The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For the CANTAB RVP, sequences of numbers must be detected as they appear on the screen. The measure of accuracy is A' (A prime) which is derived from hits and correct rejections. The maximum score is 1 and, a higher A' indicates better performance.; Impairment cutoff: < 0.82 (based on the comparison group as a whole and expressed as raw score).; For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).	6 months
Secondary	6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) SOC (Stockings of Cambridge Task) - Impaired	The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For the CANTAB SOC, the individual moves circles to match a target in this task based on the Tower of Hanoi game. The score is the number of problems solved in the minimum number of moves, with a maximum of 12. Higher scores indicate better performance.; Impairment cutoff: < 5.7(based on the comparison group as a whole and expressed as raw score).; For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).	6 months
Secondary	6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) AST (Attention Switching Task ) - Impaired	The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For the CANTAB AST, participants respond either to the position of an arrow or the direction it is pointing, after being cued to the task on each trial. Total correct responses range from 0 to 160, where higher numbers indicate better performance.; Impairment cutoff: <135.5 (based on the comparison group as a whole and expressed as raw score).; For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).	6 months
Secondary	Early (2-3 Weeks) MRI Imaging - Traumatic Intracranial Abnormalities	A selected number of sites performed MRI follow up in a subset of patients that consented for imaging data collection. The CENTER-TBI MR protocols included a high-resolution 3D T1-weighted, a T2-weighted, a FLAIR, a DTI, a T2* sequence (gradient echo and/or SWI), and (optionally) a resting-state fMRI. Across all stratum the MRI sites performed a follow up MRI at 2-3 weeks after injury.; Traumatic Intracranial Abnormalities were assessed according to the TBI-Common Data Elements (CDEs). It indicates whether any of the 12 following imaging abnormalities are present (Mass lesion, Extra-axial Hematoma, Epidural Hematoma, Subdural Hematoma Acute, Subdural Hematoma Subacute Chronic, Subdural Collection Mixed Density, Contusion, TAI, traumatic Subarachnoid Hemorrhage, Intraventricular Hemorrhage, Midline Shift or Cisternal Compression.	Between 2-3 weeks after enrolment

External Links

•   CENTER - TBI website