Table 1. Characteristics of Cohorts and Clinical Trials.

	Sepsis Endotyping in Emergency Care (SENECA)a		Genetic and Inflammatory Markers of Sepsis (GenIMS)9	A Controlled Comparison of Eritoran in Severe Sepsis (ACCESS)6	Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS)8	Protocol-Based Care for Early Septic Shock (ProCESS)7
	Derivation Cohort	Validation Cohort
No. of patients	20 189	43 086	583	1706b	1690	1341
No. of sites	12	12	28	197	164	31
Enrollment period	2010-2012	2013-2014	2001-2003	2006-2010	1998-2000	2008-2013
Location of enrollment	ED	ED	ED	ED, medical ward, ICU	ED, medical ward, ICU	ED
Primary intervention	None	None	None	Eritoran (toll-like receptor 4 antagonist) vs placebo	Drotrecogin alfa (activated protein C) vs placebo	EGDT as standard care vs usual care
Primary outcome	28-d mortalityc	28-d mortalityc	28-d mortality	28-d mortality	28-d mortality	60-d mortality
Inclusion criteria	Sepsis-3 criteria (defined as both a body fluid culture and administration of antibiotics plus ≥2 SOFA points within first 6 h after ED arrival)	Sepsis-3 criteria (defined as both a body fluid culture and administration of antibiotics plus ≥2 SOFA points within first 6 h after ED arrival)	Community-acquired pneumonia with severe sepsis (defined by Sepsis-2 criteria and ≥3 SOFA points)	Severe sepsis and septic shock (defined as meeting ≥3 SIRS criteria, dysfunction in ≥1 organ, and APACHE II score of 21-37)	Severe sepsis and septic shock (defined as meeting ≥3 SIRS criteria and dysfunction in ≥1 organ)	Severe sepsis or septic shock (defined as meeting ≥2 SIRS criteria and either serum lactate level ≥4 mmol/L or refractory hypotension)

Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; ED, emergency department; EGDT, early goal-directed therapy; ICU, intensive care unit; SIRS, systemic inflammatory response syndrome; SOFA, Sequential Organ Failure Assessment.

^aThere were 16 552 unique patients among 20 189 total patients in the derivation cohort and 31 160 unique patients among 43 086 total patients in the validation cohort.

^bIndicates total with available data.

^cMeasured among unique patients in each cohort.