---
title: "Performance of the CBI-M Framework in CENTER-TBI and TRACK-TBI Cohorts"
id: "plos-medicine-0-the-cbi-m-framework-for-characterization-of-traumatic-brain-injury-evaluation"
canonical_url: "https://medichelpline.com/clinical-feed/plos-medicine-0-the-cbi-m-framework-for-characterization-of-traumatic-brain-injury-evaluation"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "PLOS Medicine"
source_url: "https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004945"
published_at: "2026-10-20T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Performance of the CBI-M Framework in CENTER-TBI and TRACK-TBI Cohorts
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-medicine-0-the-cbi-m-framework-for-characterization-of-traumatic-brain-injury-evaluation
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** PLOS Medicine
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004945)
- **Published At:** 2026-10-20T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The CBI-M Framework combines four pillars: **Clinical**, **Biomarker**, **Imaging**, and **Modifier** to characterize acute traumatic brain injury (TBI). - Investigators applied the framework to two prospective cohorts: **CENTER-TBI** (N = 4,509) and **TRACK-TBI** (N = 2,552); data came from high-income settings. - Primary clinical endpoints included CT-defined traumatic intracranial injury, hospital and ICU admission, intracranial pressure monitoring, major cranial surgery, 6-month mortality, 6-month Glasgow Outcome Scale-Extended (GOSE), and health-related quality of life (HRQoL). - Discrimination for diagnostic and care-path endpoints was strong: full CBI-M models achieved AUCs ranging approximately from the low 0.80s to high 0.90s across cohorts; explained variability (Nagelkerke’s pseudo-R2) was high for these endpoints. - Pillar contributions varied by endpoint: the **Biomarker** pillar associated most with CT abnormalities; the **Imaging** pillar contributed most to predicting major cranial surgery; clinical features and modifiers influenced long-term outcomes. - For 6-month mortality and unfavorable GOSE, full CBI-M models showed high AUCs (roughly 0.89–0.95) and substantial pseudo-R2 values, with performance comparable to or exceeding IMPACT-Lab and CRASH-CT within their target populations. - Prognostic performance for HRQoL was modest compared with mortality and GOSE. - Study limitations reported by the authors: analyses restricted to high-income datasets, absence of three modifier components in the available data, potential reverse causality in some analyses, and retrospective analytic design within prospectively collected cohorts. - Authors recommend further prospective validation, optimization, and potential refinement and weighting of pillar elements before clinical implementation.
## Clinical Analysis & Structured Key Points
[ Skip to main content ](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004945#main-content) Advertisement * [plos.org](https://plos.org/) * [Create account](https://community.plos.org/registration/new) * [Sign in](https://journals.plos.org/user/secure/login?page=%2Fplosmedicine%2Farticle%3Fid%3D10.1371%2Fjournal.pmed.1004945) * * About * Browse * Publish * [](https://journals.plos.org/plosmedicine/ "PLOS Medicine") * Search [advanced search](https://journals.plos.org/plosmedicine/search) * 0 [Save](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1004945#savedHeader) [Total Mendeley and Citeulike bookmarks.](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1004945#savedHeader) * 0 [Citation](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1004945#citedHeader) [Paper's citation count computed by Dimensions.](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1004945#citedHeader) * 60 [View](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1004945#viewedHeader) [PLOS views and downloads.](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1004945#viewedHeader) * 0 [Share](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1004945#discussedHeader) [Sum of Facebook, Twitter, Reddit and Wikipedia activity.](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1004945#discussedHeader) Open Access Peer-reviewed Research Article # The CBI-M framework for characterization of traumatic brain injury: Evaluation of performance using data from the CENTER-TBI and TRACK-TBI prospective cohort studies * Dana Pisică , Roles Formal analysis, Methodology, Software, Visualization, Writing – original draft, Writing – review & editing ¶‡ DP, AM, and JKY share first authorship on this work. HFL, GTM, and AIRM share last authorship on this work. Affiliations Department of Public Health, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands, Department of Neurosurgery, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands ⨯ * Ana Mikolić , Roles Methodology, Writing – original draft, Writing – review & editing ¶‡ DP, AM, and JKY share first authorship on this work. HFL, GTM, and AIRM share last authorship on this work. Affiliation Department of Public Health, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-3476-096X ](https://orcid.org/0000-0002-3476-096X "ORCID Registry") ⨯ * John K. Yue , Roles Conceptualization, Writing – original draft, Writing – review & editing ¶‡ DP, AM, and JKY share first authorship on this work. HFL, GTM, and AIRM share last authorship on this work. Affiliations Department of Neurological Surgery, University of California, San Francisco, California, United States of America, Brain and Spinal Injury Center, Zuckerberg San Francisco General Hospital, San Francisco, California, United States of America [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0001-9694-7722 ](https://orcid.org/0000-0001-9694-7722 "ORCID Registry") ⨯ * Michael A. McCrea, Roles Conceptualization, Writing – review & editing Affiliation Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0001-9791-9475 ](https://orcid.org/0000-0001-9791-9475 "ORCID Registry") ⨯ * Kristen Dams-O’Connor, Roles Conceptualization, Writing – review & editing Affiliations Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America, Departments of Neuroscience and Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America ⨯ * Véronique De Keyser, Roles Project administration, Writing – review & editing Affiliation Department of Neurosurgery, Antwerp University Hospital, Edegem, Belgium [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0009-0005-0777-8370 ](https://orcid.org/0009-0005-0777-8370 "ORCID Registry") ⨯ * Sonia Jain, Roles Formal analysis, Software, Writing – review & editing Affiliation Biostatistics Research Center, Herbert Wertheim School of Public Health and Longevity Science, University of California, San Diego, California, United States of America [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0001-8408-1247 ](https://orcid.org/0000-0001-8408-1247 "ORCID Registry") ⨯ * Amy J. Markowitz, Roles Project administration, Writing – review & editing Affiliations Department of Neurological Surgery, University of California, San Francisco, California, United States of America, Brain and Spinal Injury Center, Zuckerberg San Francisco General Hospital, San Francisco, California, United States of America [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0001-9314-2814 ](https://orcid.org/0000-0001-9314-2814 "ORCID Registry") ⨯ * David K. Menon, Roles Conceptualization, Writing – review & editing Affiliation Department of Medicine, University of Cambridge, Cambridge, United Kingdom [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-3228-9692 ](https://orcid.org/0000-0002-3228-9692 "ORCID Registry") ⨯ * Virginia Newcombe, Roles Conceptualization, Writing – review & editing Affiliation Department of Medicine, University of Cambridge, Cambridge, United Kingdom ⨯ * Ewout W. Steyerberg, Roles Methodology, Writing – review & editing Affiliation Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-7787-0122 ](https://orcid.org/0000-0002-7787-0122 "ORCID Registry") ⨯ * Xiaoying Sun, Roles Formal analysis, Software, Writing – review & editing Affiliation Biostatistics Research Center, Herbert Wertheim School of Public Health and Longevity Science, University of California, San Diego, California, United States of America ⨯ * Hester F. Lingsma , Roles Methodology, Supervision, Writing – review & editing ¶‡ DP, AM, and JKY share first authorship on this work. HFL, GTM, and AIRM share last authorship on this work. Affiliation Department of Public Health, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0003-2063-9533 ](https://orcid.org/0000-0003-2063-9533 "ORCID Registry") ⨯ * Geoffrey T. Manley , Roles Conceptualization, Supervision, Writing – original draft, Writing – review & editing * E-mail: manleyg@ucsf.edu ¶‡ DP, AM, and JKY share first authorship on this work. HFL, GTM, and AIRM share last authorship on this work. Affiliations Department of Neurological Surgery, University of California, San Francisco, California, United States of America, Brain and Spinal Injury Center, Zuckerberg San Francisco General Hospital, San Francisco, California, United States of America [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-0926-3128 ](https://orcid.org/0000-0002-0926-3128 "ORCID Registry") ⨯ * Andrew I. R. Maas , Roles Conceptualization, Supervision, Writing – original draft, Writing – review & editing ¶‡ DP, AM, and JKY share first authorship on this work. HFL, GTM, and AIRM share last authorship on this work. Affiliations Department of Neurosurgery, Antwerp University Hospital, Edegem, Belgium, Department of Translational Neuroscience, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, Belgium [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0003-1612-1264 ](https://orcid.org/0000-0003-1612-1264 "ORCID Registry") ⨯ * [ ... ], * on behalf of the CENTER-TBI and TRACK-TBI Investigators ¶Membership of [CENTER-TBI and TRACK-TBI Investigators] is provided in Supporting information file S1 Text. ⨯ * [ view all ] * [ view less ] # The CBI-M framework for characterization of traumatic brain injury: Evaluation of performance using data from the CENTER-TBI and TRACK-TBI prospective cohort studies * Dana Pisică, * Ana Mikolić, * John K. Yue, * Michael A. McCrea, * Kristen Dams-O’Connor, * Véronique De Keyser, * Sonia Jain, * Amy J. Markowitz, … * David K. Menon, * Virginia Newcombe ![PLOS](https://journals.plos.org/resource/img/logo-plos-full-color.svg) x * Published: October 20, 2026 * * [Article](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004945) * [Authors](https://journals.plos.org/plosmedicine/article/authors?id=10.1371/journal.pmed.1004945) * [Metrics](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1004945) * [Comments](https://journals.plos.org/plosmedicine/article/comments?id=10.1371/journal.pmed.1004945) * [Media Coverage](http://plos.altmetric.com/details/doi/10.1371/journal.pmed.1004945) * [Abstract](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004945#abstract0) * [Author summary](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004945#abstract1) * [Introduction](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004945#sec007) * [Methods](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004945#sec008) * [Results](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004945#sec015) * [Discussion](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004945#sec021) * [Supporting information](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004945#sec022) * [Acknowledgments](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004945#ack) * [References](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004945#references) * [Reader Comments](https://journals.plos.org/plosmedicine/article/comments?id=10.1371/journal.pmed.1004945) * [Figures](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004945) ![Accessible Data Icon](https://journals.plos.org/resource/img/accessible_data.svg)Accessible Data [ See the data ![Link Icon](https://journals.plos.org/resource/img/data_link_icon.svg) ](https://doi.org/10.5281/zenodo.22725200) This article includes the Accessible Data icon, an experimental feature to encourage data sharing and reuse. [Find out how research articles qualify for this feature.](https://theplosblog.plos.org/2023/07/accessible-data/) ## Abstract ### Background The CBI-M Framework, incorporating Clinical, Biomarker, Imaging, and Modifier pillars, was recently proposed to provide a comprehensive characterization of patients with acute traumatic brain injury (TBI). Such detailed characterization reflects the clinical and biological heterogeneity of TBI, and is considered essential to inform appropriate clinical management. Still unclear is the extent to which CBI-M captures clinically relevant heterogeneity in relation to diagnosis, clinical care pathways, and longer-term outcome. Prior to broad implementation into clinical practice and research, its diagnostic and prognostic performance needs to be ascertained. In this study, we aim to explore how CBI-M and its constituent pillars relate to diagnosis, clinical care pathways, and outcome in two large contemporary TBI cohorts. ### Methods and findings We analyzed data of patients with acute TBI enrolled in the European-based CENTER-TBI (_N_ = 4,509) and US-based TRACK-TBI (_N_ = 2,552) prospective observational studies. We assessed associations of the CBI-M Framework, its pillars, and pillar components with key clinical endpoints: diagnosis (traumatic intracranial injury on computed tomography); care pathways (hospital admission, intensive care admission, intracranial pressure monitoring, and major cranial surgery); and outcomes at 6 months post-injury (mortality, Glasgow Outcome Scale-Extended (GOSE), and health-related quality of life (HRQoL)). Discriminatory performance was calculated using the AUC and explained variability expressed with Nagelkerke’s pseudo-R2. Prognostic performance was compared to the established IMPACT-Lab and CRASH-CT prediction models in their respective target populations. For diagnostic and care path endpoints full CBI-M models achieved excellent discrimination (AUC CENTER-TBI: from 0.83 to 0.95; TRACK-TBI: from 0.88 to 0.98), and high proportions of explained variability (pseudo-R2 CENTER-TBI: from 0.41 to 0.72; TRACK-TBI: from 0.55 to 0.80). Contributions of individual pillars varied by endpoint, with the Biomarker pillar contributing most for CT-defined abnormalities and the Imaging pillar to major cranial surgery. For mortality and unfavorable outcome (GOSE ≤ 4) similarly strong performance was observed: CENTER-TBI: AUC 0.89 (95% Confidence intervals (CI) [0.88,0.90]) and 0.92 (95% CI [0.91,0.94]) respectively; pseudo-R2 0.53 (95% CI [0.50,0.57]) and 0.55 (95% CI [0.51,0.59]) respectively; TRACK-TBI: AUC 0.91 (95% CI [0.89,0.93]) and 0.95 (95% CI [0.93,0.97]) respectively; pseudo-R2 0.57 (95% CI [0.52,0.62] and 0.57 (95% CI [0.50, 0.64] respectively), whereas performance for HRQoL was modest. Compared to the IMPACT-Lab and CRASH-CT models in their respective target populations, pseudo-R2 values suggest that the full CBI-M model was more strongly associated with 6-month mortality and unfavorable outcomes. Methodological limitations include the restriction to analysis of data from high-income settings, limiting generalizability, the absence of three elements of the modifier pillar in the datasets accessed, and risk of possible reverse causality in some analyses. ### Conclusions CBI-M provides a robust multimodal characterization of acute TBI that aligns closely with clinical decision-making and outcomes. Further prospective validation and optimization are justified and needed to inform implementation of the CBI-M Framework in clinical practice and research. ## Author summary ### Why was this study done? * Traumatic brain injury (TBI) is a complex and heterogeneous condition. * The complexity of the disease is poorly captured by the traditional approach to classification, which is based only on clinical severity and groups patients into three categories of mild, moderate, or severe. * A new framework (CBI-M) has been proposed to better describe TBI using clinical features, blood biomarkers, imaging findings, and modifiers. * It is not yet known whether this framework meaningfully reflects how patients are diagnosed, treated, and recover in real-world clinical settings. ### What did the researchers do and find? * We analyzed data from over 7,000 patients with TBI enrolled in two large international studies (CENTER-TBI and TRACK-TBI). * We found that the CBI-M framework closely aligned with clinical decision-making, including diagnosis, hospital care pathways, and outcomes at 6 months. * Different components of the framework contributed in different ways: clinical, biomarker, and imaging features were most relevant for early care decisions, while patient-related factors were more important for longer-term recovery and quality of life. ### What do these findings mean? * These results provide empirical support for the potential clinical relevance of the CBI-M framework, and support further development towards clinical and research use. * Whilst its applicability across all ranges of clinical severity is a strength, some elements of a pillar may be more relevant in less severely injured patients and others in more severely injured patients. * Steps towards clinical implementation should include prospective validation, combined with refining and weighting of pillar elements. * Limitations of the study include its retrospective nature, the restriction to data from high-income countries and lack of data on three basic components of the modifier pillar. ## Figures ![Fig 2](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1004945.g002) ![Fig 3](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1004945.g003) ![Fig 4](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1004945.g004) ![Table 1](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1004945.t001) ![Fig 1](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1004945.g001) ![Table 2](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1004945.t002) ![Fig 2](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1004945.g002) ![Fig 3](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1004945.g003) ![Fig 4](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1004945.g004) ![Table 1](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1004945.t001) ![Fig 1](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1004945.g001) ![Table 2](https://journals.plos.org/plosmedicine/article/figure/image?size=inline&id=10.1371/journal.pmed.1004945.t002) **Citation:** Pisică D, Mikolić A, Yue JK, McCrea MA, Dams-O’Connor K, De Keyser V, et al. (2026) The CBI-M framework for characterization of traumatic brain injury: Evaluation of performance using data from the CENTER-TBI and TRACK-TBI prospective cohort studies. PLoS Med 23(10): e1004945. https://doi.org/10.1371/journal.pmed.1004945 **Academic Editor:** Karim Brohi, Barts and the London School of Medicine & Dentistry Queen Mary University of London, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND **Received:** January 30, 2026; **Accepted:** September 17, 2026; **Published:** October 20, 2026 **Copyright:** © 2026 Pisică et al. This is an open access article distributed under the terms of the [Creative Commons Attribution License](http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. **Data Availability:** The data underlying the results presented in the study are not publicly available. The individual-level CENTER-TBI and TRACK-TBI data contain sensitive participant information and are subject to ethical and contractual restrictions designed to protect participant privacy and confidentiality and to ensure that data are used in accordance with the conditions of participant consent and applicable Data Use Agreements. For de-identified CENTER-TBI data, data access applications can be made to the CENTER-TBI Management Committee ( ) [accessed 07/13/2026]. Access will be granted after approval of a Study Plan proposal and signing a data Use Agreement. De-identified TRACK-TBI data are available by request from the Open Data Commons for Traumatic Brain Injury ( ) [accessed 07/13/2026]. Access will be granted after approval of a Study Plan proposal and signing a Data Use Agreement. The code used in the analysis is available
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