Prognostic Research in Traumatic Brain Injury: Markers, Modeling, and Methodological Principles

Isabel R.A.Retel Helmrich*, Hester F. Lingsma, Alexis F. Turgeon, Jose Miguel Yamal, Ewout W. Steyerberg

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Scopus)
96 Downloads (Pure)


Prognostic assessment in traumatic brain injury (TBI) is embedded deeply in clinical care. Considering the limitations of current prognostic indicators, there is increasing interest in understanding the role of new biomarkers, and in finding other prognostic indicators of long-term outcomes following TBI. New prognostic indicators may result in the development of more accurate prediction models that could be useful for both risk stratification and clinical decision making. We aimed to review methodological issues and provide tentative guidelines for prognostic research in TBI. Prognostic factor research focuses on the role of a specific patient or disease-related characteristic in relation to outcome. Typically, univariable relations of the prognostic factor are studied, followed by analyses adjusting for other variables related to the outcome. Following existing guidelines, we emphasize the importance of transparent reporting of patient and specimen characteristics, study design, clinical end-points, and statistical analysis. Prognostic model research considers combinations of predictors, with challenges for model specification, estimation, evaluation, validation, and presentation. We highlight modern approaches and opportunities related to missing values, exploration of non-linear effects, and assessing between-study heterogeneity. Prognostic research in TBI can be improved if key methodological principles are adhered to and when research is performed in collaboration among multiple centers to ensure generalizability.

Original languageEnglish
Pages (from-to)2502-2513
Number of pages12
JournalJournal of Neurotrauma
Issue number18
Early online date23 Aug 2021
Publication statusPublished - 15 Sept 2021

Bibliographical note

Funding Information:
I.R.A.R.H., H.F.L., and E.W.S. were supported by the European Union 7th Framework program (CENTER-TBI, EC grant 602150). A.F.T. is the chairholder of the Canada Research Chair in Critical Care Neurology and Trauma and is supported by the Canadian Institutes of Health Research (CIHR) (TBI-Prognosis study, CIHR grant #275553 and CIHR Foundation Scheme Grant # 354039; HEMOglobin Transfusion Threshold in Traumatic Brain Injury OptimizatioN [HEMOTION] Trial, CHIR grant #367141).

Publisher Copyright:
© Isabel R.A. Retel Helmrich et al., 2021; Published by Mary Ann Liebert, Inc. 2021.


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