• Christopher W Seymour, Colin R Cooke, Zheyu Wang, Kathleen F Kerr, Donald M Yealy, Derek C Angus, Thomas D Rea, Jeremy M Kahn, and Margaret S Pepe.
• Departments of Critical Care and Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care, Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: seymourcw@upmc.edu.
• J Crit Care. 2013 Oct 1; 28 (5): 541-8.

PurposeOptimal triage of patients at risk for critical illness requires accurate risk prediction, yet few data on the performance criteria required of a potential biomarker to be clinically useful exists.Materials And MethodsWe studied an adult cohort of nonarrest, nontrauma emergency medical services encounters transported to a hospital from 2002 to 2006. We simulated hypothetical biomarkers increasingly associated with critical illness during hospitalization and determined the biomarker strength and sample size necessary to improve risk classification beyond a best clinical model.ResultsOf 57,647 encounters, 3121 (5.4%) were hospitalized with critical illness and 54,526 (94.6%) without critical illness. The addition of a moderate-strength biomarker (odds ratio, 3.0, for critical illness) to a clinical model improved discrimination (c statistic, 0.85 vs 0.8; P<.01) and reclassification (net reclassification improvement, 0.15; 95% confidence interval, 0.13-0.18) and increased the proportion of cases in the highest-risk category by +8.6% (95% confidence interval, 7.5%-10.8%). Introducing correlation between the biomarker and physiological variables in the clinical risk score did not modify the results. Statistically significant changes in net reclassification required a sample size of at least 1000 subjects.ConclusionsClinical models for triage of critical illness could be significantly improved by incorporating biomarkers, yet substantial sample sizes and biomarker strength may be required.Copyright © 2013 Elsevier Inc. All rights reserved.

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