Opportunities and Challenges in High-Quality Contemporary Data Collection in Traumatic Brain Injury: The CENTER-TBI Experience.

Strong evidence in support of guidelines for traumatic brain injury (TBI) is lacking. Large-scale observational studies may offer a complementary source of evidence to clinical trials to improve the care and outcome for patients with TBI. They are, however, challenging to execute. In this review, we aim to characterize opportunities and challenges of large-scale collaborative research in neurotrauma. We use the setup and conduct of Collaborative European Neurotrauma Effectiveness Research in TBI (CENTER-TBI) as an illustrative example. We highlight the importance of building a team and of developing a network for younger researchers, thus investing toward the future. We involved investigators early in the design phase and recognized their efforts in a group contributor list on all publications. We found, however, that translation to academic credits often failed, and we suggest that the current system of academic credits be critically appraised. We found substantial variability in consent procedures for participant enrollment within and between countries. Overall, obtaining approvals typically required 4-6 months, with outliers up to 18 months. Research costs varied considerably across Europe and should be defined by center. We substantially underestimated costs of data curation, and we suggest that 15-20% of the budget be reserved for this purpose. Streamlining analyses and accommodating external research proposals demanded a structured approach. We implemented a systematic inventory of study plans and found this effective in maintaining oversight and in promoting collaboration between research groups. Ensuring good use of the data was a prominent feature in the review of external proposals. Multiple interactions occurred with industrial partners, mainly related to biomarkers and neuroimaging, and resulted in various formal collaborations, substantially extending the scope of CENTER-TBI. Overall, CENTER-TBI has been productive, with over 250 international peer-reviewed publications. We have ensured mechanisms to maintain the infrastructure and continued analyses. We see potential for individual patient data meta-analyses in connection to other large-scale projects. Our collaboration with Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) has taught us that although standardized data collection and coding according to common data elements can facilitate such meta-analyses, further data harmonization is required for meaningful results. Both CENTER-TBI and TRACK-TBI have demonstrated the complexity of the conduct of large-scale collaborative studies that produce high-quality science and new insights.

Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study.

BACKGROUND: The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI. METHODS: CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582). FINDINGS: Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13-15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30-66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOSE <8) was found in 207 (30%) patients in the ER stratum, 665 (53%) in the admission stratum, and 1547 (84%) in the ICU stratum. Among patients with moderate-to-severe TBI in the ICU stratum, 623 (55%) patients had unfavourable outcome at 6 months (GOSE <5), similar to the proportion predicted by the IMPACT prognostic model (observed to expected ratio 1·06 [95% CI 0·97-1·14]), but mortality was lower than expected (0·70 [0·62-0·76]). INTERPRETATION: Patients with TBI who presented to European centres in the core study were older than were those in previous observational studies and often had comorbidities. Overall, most patients presented with mild TBI. The incomplete recovery of many patients should motivate precision medicine research and the identification of best practices to improve these outcomes. FUNDING: European Union 7th Framework Programme, the Hannelore Kohl Stiftung, OneMind, and Integra LifeSciences Corporation.

Prospective issues for error detection.

From the literature on error detection, the authors select several concepts relating error detection mechanisms and prospective memory features. They emphasize the central role of intention in the classification of the errors into slips/lapses/mistakes, in the error handling process and in the usual distinction between action-based and outcome-based detection. Intention is again a core concept in their investigation of prospective memory theory, where they point out the contribution of intention retrievals, intention persistence and output monitoring in the individual's possibilities for detecting their errors. The involvement of the frontal lobes in prospective memory and in error detection is also analysed. From the chronology of a prospective memory task, the authors finally suggest a model for error detection also accounting for neural mechanisms highlighted by studies on error-related brain activity.