Background Traumatic brain injury (TBI) is a leading cause of death and disability. A reliable prediction of outcome on admission is of great clinical relevance. We aimed to develop prognostic models with readily available traditional and novel predictors. Methods and Findings Prospectively collected individual patient data were analyzed from 11 studies. We considered predictors available at admission in logistic regression models to predict mortality and unfavorable outcome according to the Glasgow Outcome Scale at 6 mo after injury. Prognostic models were developed in 8,509 patients with severe or moderate TBI, with cross-validation by omission of each of the 11 studies in turn. External validation was on 6,681 patients from the recent Medical Research Council Corticosteroid Randomisation after Significant Head Injury (MRC CRASH) trial. We found that the strongest predictors of outcome were age, motor score, pupillary reactivity, and CT characteristics, including the presence of traumatic subarachnoid hemorrhage. A prognostic model that combined age, motor score, and pupillary reactivity had an area under the receiver operating characteristic curve (AUC) between 0.66 and 0.84 at cross-validation. This performance could be improved (AUC increased by approximately 0.05) by considering CT characteristics, secondary insults (hypotension and hypoxia), and laboratory parameters (glucose and hemoglobin). External validation confirmed that the discriminative ability of the model was adequate (AUC 0.80). Outcomes were systematically worse than predicted, but less so in 1,588 patients who were from high-income countries in the CRASH trial. Conclusions Prognostic models using baseline characteristics provide adequate discrimination between patients with good and poor 6 mo outcomes after TBI, especially if CT and laboratory findings are considered in addition to traditional predictors. The model predictions may support clinical practice and research, including the design and analysis of randomized controlled trials.
References
[1]
Teasdale G, Jennett B (1974) Assessment of coma and impaired consciousness. A practical scale. Lancet 2: 81–84.
[2]
Jennett B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet 1: 480–484.
[3]
Jennett B, Teasdale G, Braakman R, Minderhoud J, Knill-Jones R (1976) Predicting outcome in individual patients after severe head injury. Lancet 1: 1031–1034.
[4]
Machado SG, Murray GD, Teasdale GM (1999) Evaluation of designs for clinical trials of neuroprotective agents in head injury. European Brain Injury Consortium. J Neurotrauma 16: 1131–1138.
[5]
Hernandez AV, Steyerberg EW, Taylor GS, Marmarou A, Habbema JD, et al. (2005) Subgroup analysis and covariate adjustment in randomized clinical trials of traumatic brain injury: a systematic review. Neurosurgery 57: 1244–1253.
[6]
Hernandez AV, Steyerberg EW, Butcher I, Mushkudiani N, Taylor GS, et al. (2006) Adjustment for strong predictors of outcome in traumatic brain injury trials: 25% reduction in sample size requirements in the IMPACT study. J Neurotrauma 23: 1295–1303.
[7]
Perel P, Edwards P, Wentz R, Roberts I (2006) Systematic review of prognostic models in traumatic brain injury. BMC Med Inform Decis Mak 6: 38.
[8]
Mushkudiani NA, Hukkelhoven CW, Hernandez AV, Murray GD, Choi SC, et al. (2008) A systematic review finds methodological improvements necessary for prognostic models in determining traumatic brain injury outcomes. J Clin Epidemiol 61: 331–343.
[9]
Justice AC, Covinsky KE, Berlin JA (1999) Assessing the generalizability of prognostic information. Ann Intern Med 130: 515–524.
[10]
Reilly BM, Evans AT (2006) Translating clinical research into clinical practice: impact of using prediction rules to make decisions. Ann Intern Med 144: 201–209.
[11]
Maas AI, Marmarou A, Murray GD, Teasdale SG, Steyerberg EW (2007) Prognosis and clinical trial design in traumatic brain injury: the IMPACT study. J Neurotrauma 24: 232–238.
[12]
Murray GD, Butcher I, McHugh GS, Lu J, Mushkudiani NA, et al. (2007) Multivariable prognostic analysis in traumatic brain injury: results from the IMPACT study. J Neurotrauma 24: 329–337.
[13]
Edwards P, Arango M, Balica L, Cottingham R, El-Sayed H, et al. (2005) Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months. Lancet 365: 1957–1959.
[14]
MRC CRASH Trial Collaborators,Perel P, Arango M, Clayton T, Edwards P, et al. (2008) Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients. BMJ 336: 425–429.
[15]
Marmarou A, Lu J, Butcher I, McHugh GS, Mushkudiani NA, et al. (2007) IMPACT database of traumatic brain injury: design and description. J Neurotrauma 24: 239–250.
[16]
Marshall LF, Marshall SB, Klauber MR, Van Berkum Clark M, Eisenberg H, et al. (1992) The diagnosis of head injury requires a classification based on computed axial tomography. J Neurotrauma 9(Suppl 1): S287–292.
[17]
McHugh GS, Butcher I, Steyerberg EW, Lu J, Mushkudiani N, et al. (2007) Statistical approaches to the univariate prognostic analysis of the IMPACT database on traumatic brain injury. J Neurotrauma 24: 251–258.
[18]
Rubin DB, Schenker N (1991) Multiple imputation in health-care databases: an overview and some applications. Stat Med 10: 585–598.
[19]
Schafer JL, Graham JW (2002) Missing data: our view of the state of the art. Psychol Methods 7: 147–177.
[20]
Enders CK (2006) A primer on the use of modern missing-data methods in psychosomatic medicine research. Psychosom Med 68: 427–436.
[21]
Van Buuren S, Oudshoorn CGM (2006) mice: Multivariate Imputation by Chained Equations. R package version 1.16. Available: http://web.inter.nl.net/users/S.vanBuure?n/mi/hmtl/mice.htm. Accessed 12 December 2006.
[22]
R Development Core Team (2006) R: A language and environment for statistical computing. Vienna (Austria): R Foundation for Statistical Computing. Available: http://www.R-project.org/. Accessed 30 June 2008.
[23]
McCullagh P (1980) Regression models for ordinal data. J R Stat Soc Ser B 42: 109–142.
[24]
Harrell FE (2001) Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis. New York: Springer. 568 pp.
[25]
Harrell FE (2006) Design: Design Package. R package version 2.0. http://biostat.mc.vanderbilt.edu/s/Desig?n. Accessed 30 June 2008.
[26]
Vergouwe Y, Steyerberg EW, Eijkemans MJ, Habbema JD (2005) Substantial effective sample sizes were required for external validation studies of predictive logistic regression models. J Clin Epidemiol 58: 475–483.
[27]
Moons KG, Harrell FE, Steyerberg EW (2002) Should scoring rules be based on odds ratios or regression coefficients. J Clin Epidemiol 55: 1054–1055.
[28]
Maas AI, Hukkelhoven CW, Marshall LF, Steyerberg EW (2005) Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and combinations of computed tomographic predictors. Neurosurgery 57: 1173–1182.
[29]
Van Beek JG, Mushkudiani NA, Steyerberg EW, Butcher I, McHugh GS, et al. (2007) Prognostic value of admission laboratory parameters in traumatic brain injury: results from the IMPACT study. J Neurotrauma 24: 315–328.
[30]
van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, et al. (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345: 1359–1367.
[31]
Signorini DF, Andrews PJ, Jones PA, Wardlaw JM, Miller JD (1999) Predicting survival using simple clinical variables: a case study in traumatic brain injury. J Neurol Neurosurg Psychiatry 66: 20–25.
[32]
Schreiber MA, Aoki N, Scott BG, Beck JR (2002) Determinants of mortality in patients with severe blunt head injury. Arch Surg 137: 285–290.
[33]
Lemeshow S, Le Gall JR (1994) Modeling the severity of illness of ICU patients. A systems update. JAMA 272: 1049–1055.
[34]
Cho DY, Wang YC (1997) Comparison of the APACHE III, APACHE II and Glasgow coma scale in acute head injury for prediction of mortality and functional outcome. Intensive Care Med 23: 77–84.
[35]
Hyam JA, Welch CA, Harrison DA, Menon DK (2006) Case mix, outcomes and comparison of risk prediction models for admissions to adult, general and specialist critical care units for head injury: a secondary analysis of the ICNARC Case Mix Programme Database. Crit Care 10(Suppl 2): S2.
[36]
Choi SC (1998) Sample size in clinical trials with dichotomous endpoints: use of covariables. J Biopharm Stat 8: 367–375.
[37]
Murray GD, Barer D, Choi S, Fernandes H, Gregson B, et al. (2005) Design and analysis of phase III trials with ordered outcome scales: the concept of the sliding dichotomy. J Neurotrauma 22: 511–517.
[38]
Lemeshow S, Klar J, Teres D (1995) Outcome prediction for individual intensive care patients: useful, misused, or abused. Intensive Care Med 21: 770–776.
[39]
Murray LS, Teasdale GM, Murray GD, Jennett B, Miller JD, et al. (1993) Does prediction of outcome alter patient management. Lancet 341: 1487–1491.
[40]
Hukkelhoven CW, Steyerberg EW, Farace E, Habbema JD, Marshall LF, et al. (2002) Regional differences in patient characteristics, case management, and outcomes in traumatic brain injury: experience from the tirilazad trials. J Neurosurg 97: 549–557.
[41]
Steyerberg EW, Borsboom GJ, van Houwelingen HC, Eijkemans MJ, Habbema JD (2004) Validation and updating of predictive logistic regression models: a study on sample size and shrinkage. Stat Med 23: 2567–2586.
[42]
Steyerberg EW (2005) Local applicability of clinical and model-based probability estimates. Med Decis Making 25: 678–680.
[43]
Moons KG, Donders RA, Stijnen T, Harrell FE Jr. (2006) Using the outcome for imputation of missing predictor values was preferred. J Clin Epidemiol 59: 1092–1101.