Community Research and Development Information Service - CORDIS

Periodic Report Summary 3 - CREACTIVE (Collaborative REsearch on ACute Traumatic brain Injury in intensiVe care medicine in Europe)

Project Context and Objectives:
Traumatic brain injury (TBI) is defined as an alteration in brain function, or other evidence of brain pathology, caused by an external force. It is a leading cause of death and disability and the main cause of death among the under-45s. TBI can be classified as mild, moderate, and severe, based on assessment of the level of coma, loss or alteration of consciousness, duration of post-traumatic amnesia, and neuroimaging results. While mild TBI patients are variably managed in the different health services, most moderate and almost all severe TBI patients who manage to reach a hospital are admitted to an intensive care unit (ICU). Although these patients represent only 20% of the total, they carry the main burden of the disease. Some permanent disability is estimated to occur in 10% of mild, 66% of moderate, and 100% of severe TBIs. Estimated in-hospital mortality is <5% in mild TBI, while it increases to approximately 20% in moderate, and approximately 45% in severe cases at six months. Hence, the ICU is in an ideal position to adequately evaluate and monitor the bulk of the burden of the disease, identify and assess the most effective clinical interventions, and recognize excellence in TBI management. Moreover, even mild TBI patients can be admitted to ICUs in cases of accompanying conditions (multiple trauma, organ failure, important comorbidity, etc.).
The “PROSAFE” ICU network, established with EU funding (PHEA 2007331) to collect high quality data on all critically ill patients admitted to the ICU, is now focusing its attention specifically on TBI patients through the CREACTIVE project.

The main objectives of the project are to
- discuss and reach a consensus on the TBI data to be collected by all intensive care units participating in CREACTIVE, based on the common data elements (CDEs) endorsed by the international InTBIR initiative;
- build an eCRF designed to facilitate data sharing with the other consortia in the InTBIR Initiative;
- localise the system in the languages of the CREACTIVE consortium members;
- collect superior quality data on moderate-severe TBI patients admitted to the ICU in order to better describe the epidemiology of moderate to severe TBI in 6 European countries (Cyprus, Greece, Hungary, Italy, Poland, Slovenia) and Israel,;
- gather a large number of biological samples and imaging data in a representative epidemiological cohort;
- build a prognostic model based on clinical and biological data to predict short- and long-term outcomes;
- validate the existing prognostic scores;
- identify the most effective clinical interventions for optimally treating TBI patients;
- recognize the determinants of optimal vs. suboptimal performance;
- ensure rapid, appropriate, tailored dissemination of project output to all pertinent stakeholders in order to raise awareness and share knowledge.

Project Results:
The main achievements between October 2016 (M37) and March 2018 (M54) can be summarized as follows:

Data collection
During the 3rd reporting period, the Country Coordinators continued ICU recruitment in the respective countries. Paediatric ICUs form a subset of total recruitments and are led by the Israeli team from Ben Gurion University. Country coordinators also supervise data collection through the online monitoring system and make periodic site visits. Collection of eCRF data started on 15th March, 2014. At 31 December 2017, valid data had been collected on 6230 TBI patients.

Training
The CREACTIVE Coordinator, Country Coordinators, project managers and CREACTKids team provided training and updating in data collection and monitoring locally and at national and subgroups meetings.

Statistics and reporting
Three kinds of statistical report are generated annually: general (all project data); national (country-related status), but only for countries with at least 5 ICUs; personalised (status at each participating ICU). The reports are published in two stages: with and without follow up data. The complete data report on 2014 and 2015 data was published in December 2016 and in September 2017 for complete 2016 data. Reports are produced to describe the clinical epidemiology of TBI.
Further analyses will be focused on providing each ICU with tools to compare own quality of performance in treating TBI patients with average adjusted rates; evaluating the extent to which TBI patient outcomes depend on the resources available at the admitting facility; identifying centres of excellence in treating TBI patients to permit good exchange of practices and quality improvement; determining the most effective treatments according to patient characteristics and type of injury.

During the 3rd period, the statistics team built a 3-level polytomous prognostic model to help predict 6-month outcome based on general clinical and TBI-specific ICU admission characteristics and resources available at the admitting facility. The model serves to compare expected with observed outcomes of TBI patients in each ICU and as the base for analysis of comparative effectiveness and the impact of available resources.

Biological and imaging repositories
At the end of the 3rd period, 24 centres were participating in the circulating biomarkers substudy. Plasma and serum samples have been collected for a total of 1458 patients since 1 February, 2015

Collection of imaging data started in March 2015. In the 3rd period, a total of 1921 quality-controlled series were collected from 637 patients, after excluding series with strong artefacts. Manual segmentation of intraparenchymal haemorrhagic lesions and oedema was performed on an initial dataset of 255 series from 66 patients, and used to train a deep learning-based, dense segmentation method (U-Net) for automatic lesion and oedema segmentation and sizing. Work is ongoing to improve performance of the automated segmentation method

Clinical data on 394 out of 567 patients with an annotated lesion was extracted to the main dataset, for a total of 1204 series. The dataset has been used to study the use of raw imaging data in addition to clinical data as an input to a neural network model to predict outcome. The model is trained to recognize image-based patterns that characterize the lesion and their relation with outcome. Performance of the final model will be compared to the clinical data model developed by NEGRI, to evaluate the potential for augmenting prognostic models with imaging data

Dissemination activities
Internal and external dissemination activities have included networking meetings in Washington DC and Bethesda, and numerous teleconferences with other InTBIR consortia.

Oral and poster presentations have been made at major meetings and the second CREACTIVE symposium will be held on 13th June, 2018.

A collaboration has started with the Human Brain Project – Medical Informatics Platform to develop a platform for data sharing within European consortia of InTBIR and through the BIO-AX-TBI project to exploit CREACTIVE data

Potential Impact:
The aim of the project is to impact various stakeholders:

Scientific community

The CREACTIVE Consortium aims to contribute to the updating of the current classification of TBI which is still based on the Glasgow Coma Scale, developed almost 40 years ago when the clinical approach to TBI patients differed considerably from today.
The project will gather data on all moderate to severe patients (without any selection) and from all kinds of healthcare facilities (not restricted to highly specialized units). Such full coverage of the whole picture is an essential condition to propose an unbiased basis for the development of a new classification system of TBI. The various kinds of data will also enable the CREACTIVE consortium to analyse different types of outcome (short- and long-term mortality and disability). The integration of different multivariable models, which will be generated on the same population, will represent a unique opportunity to convincingly address the multidimensional framework of TBI.

In terms of the effectiveness of interventions, the collection of large numbers of data in its various European sites will enable the CREACTIVE Consortium to exploit its consolidated know-how in modelling complex situations and ultimately provide the wider TBI network and the scientific community in general with the best estimates of the effectiveness of treatment bundles.

The different kinds of data and samples (from the clinical characteristics of the patients to clinical imaging and biomarkers, from the available healthcare resources to the process of care adopted) relating to a large number of patients with TBI collected by the CREACTIVE project will be made available to the scientific community according to the data sharing policy endorsed by InTBIR, to perform studies.

The data sharing platform being developed in collaboration with the Human Brain Project will make CREACTIVE data exploitable by the scientific community for its own secondary analyses.

Patients and their families

Participation itself in clinical research projects has been associated with an increase in the quality of care provided. Patients will directly benefit from the planned long-term follow-up visit, where neurological and psychological sequelae of TBI, as post traumatic stress disorder, will be systematically addressed. It will provide patients with the opportunity to have their situation reviewed by health personnel, with possible admission to specific rehabilitation or social reintegration programmes that would not otherwise be put in place.

The major impact will be on future TBI patients and their families through the identification of the most appropriate interventions and determinants of best practices and the best TBI care pathway in the intensive care setting.

Healthcare providers

The production of personal, national and international annual reports on performance enable ICU providers to analyse their own results and compare their performance with that of other facilities. These reports are designed to identify areas of both strength and weakness.

By following up patients for longer than usual, providers can assess the evolution of the disability over time, patient recovery and patient and family coping strategies. This produces a wider picture of patient care, giving more meaning, direction and added value to the acute care pathway and enhancing engagement in the workplace. Ideally, medium-long-term follow-up will eventually become routine practice, impacting on the quality of life of both health professionals and patients.

Health and welfare policy makers and the pharmaceutical and biomedical industry.

The CREACTIVE project will provide evidence-based results on best practices, epidemiology, clinical interventions and outcomes in TBI patients whose implications will be discussed with health and welfare policy makers and with the pharmaceutical and biomedical industry


List of Websites:
http://www.creactive.marionegri.it/

Related information

Documents and Publications

Reported by

ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
Italy

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Life Sciences
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