Community Research and Development Information Service - CORDIS


CREACTIVE Report Summary

Project ID: 602714
Funded under: FP7-HEALTH
Country: Italy

Periodic Report Summary 2 - 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 21% in moderate, and 46% 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;
- 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 April 2015 (M13) and September 2015 (M36) can be summarized as follows:

Case report form
After extensive discussion, the ad hoc the CREACTIVE Follow-Up Advisory Board also reached a consensus on the items to include in the structured and semi-structured protocols to implement for the 12-month adult and the 6-month paediatric ambulatory follow-up visit which will be performed in a subset of ICUs. Translation of these final items into the consortium languages (Greek, Hungarian, Italian, Polish and Slovenian) started in the second period and was completed for the eCRF items determined in the first period. This allows providers to work in their own native tongue and removes any language barriers. IT assistance activities continued and were managed by the CREACTIVE IT ticketing system.

Since patient follow up is not part of routine practice in most participating ICUs, training courses, based on a train the trainer principle, were held for ICU providers, mainly intensive care nurses. The courses concerned both telephone follow-up carried out for all TBI patients and ambulatory follow-up, to be performed in a subset of patients.
Training in data collection was also given to ICU providers by Country Coordinators and project managers. In Italy, a group of monitors has been trained to oversee data collection and to monitor data quality and compliance in a group of ICUs.

Data collection
During the second reporting period, the Country Coordinators continued to recruit ICUs in their respective countries. The paediatric ICUs form a subset of total recruited ICUs and are led by the Israeli team from Ben Gurion University. Country coordinators also supervise data collection using the online monitoring system and making periodic site visits to the participating ICUs. Collection of eCRF data started on 15th March, 2014. Between 15 March 2014 and 30 September, 2016, valid data in the CREACTIVE system on 4781 TBI patients.

Statistical analysis and data reports are produced with a view to describing the clinical epidemiology of TBI in the participating countries; identifying the most effective treatments according to patient characteristics and type of injury; providing each ICU with tools designed 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 in the admitting facility; identifying centres of excellence in treating TBI patients, permitting good exchange of practices and quality improvement.
Three kinds of statistical report are generated annually: general (all project data); national (situation in each participating country); personalised (situation in each participating ICU). The reports are published in two stages: excluding follow up data and including follow up data. The 2014 data reports were published in June 2015 and February 2016, respectively. The reports on 2015 data were published in August 2016 and the complete data report will be issued in December 2016.

Biobanking and collection of patient imaging data
A specific biological repository has been established at the biobank at the Coordinator’s headquarters. Collection of biological data started on 1 February, 2015 and of imaging data in March 2015. The best candidate phenotypic biomarkers have now been defined in collaboration with the CREACTIVE Scientific Advisory Board for Biological Substudies.
During the reporting period OROBIX started the development of a methodology for automated segmentation of haemorrhagic lesions and oedema, employing state-of-the-art deep learning algorithms for biomedical image segmentation. The ultimate aim of this activity is to achieve high accuracy in the characterization of volume and shape of the haemorrhage and oedema, in order to characterize their evolution during the follow-up. In a subsequent analysis, the associations between the circulating biomarkers and imaging data by computed tomography will be investigated.

Dissemination activities
A specific CREACTIVE website has been created to give visibility to the project. Various internal and external dissemination activities have been carried out, including networking meetings in Brussels and Washington DC, and numerous teleconferences with other consortia taking part in the InTBIR Initiative.
Oral and poster presentations have been given at major meetings and the first CREACTIVE symposium was held on 21 October, 2016.
A collaboration has started with the Human Brain Project to develop a platform for data sharing within InTBIR.

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 was considerably different 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 deal with 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) related 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.

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, 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.

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