This Article  • References  • Full text PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Social Bookmarking   What's this?

A Prospective Study Design Based on Survival Analysis

William A. Knaus, MD; Frank E. Harrell, PhD; Charles J. Fisher, Jr, MD; Douglas P. Wagner, PhD; Steven M. Opal, MD; Jerald C. Sadoff, MD; Elizabeth A. Draper, MS; Cynthia A. Walawander, MA; Kathleen Conboy, MS; Thaddeus H. Grasela, PharmD

JAMA. 1993;270(10):1233-1241.

Abstract
Objective.
—To develop a survival model and severity assessment method to estimate the 28-day mortality risk for patients with sepsis syndrome entering phase 2 and 3 drug evaluations.

Design.
—Retrospective analysis of intensive care unit admissions with sepsis syndrome by means of log-normal regression to identify risk factors for 28-day mortality. Prospective application of the model to patients with gram-negative infection meeting sepsis syndrome criteria from separate data collection (validation group).

Patients.
—A total of 58 737 intensive care unit admissions at 107 hospitals in the United States and Western Europe screened to yield 1195 patients meeting entry criteria for the sepsis syndrome study for the original model; 295 hospitalized patients with gram-negative infection meeting criteria for sepsis syndrome for validation.

Main Outcome Measures.
—Survival time and mortality at 28 days after fulfillment of the sepsis syndrome criteria.

Results.
—Acute physiologic abnormalities were the most important prognostic factors influencing outcome (82% of total ²). Specific disease resulting in intensive care unit admission and the time the patient was in the hospital and intensive care unit before qualification were also independent risks, as were age and a clinical history of cirrhosis. The model's overall classification accuracy was a Somers' Dyx of .52 (rank correlation between predicted risk and 28-day mortality) (receiver operating characteristic area, 0.76), with equal accuracy (Dyx=.59; receiver operating characteristic area, 0.80) in the independent group of patients.

Conclusions.
—We created an accurate independent estimate for 28-day mortality risk for patients with sepsis syndrome (severe sepsis). This estimate could improve the evaluation of new drugs by investigating whether the drug's benefit varies by patient risk and then determining the amount of benefit for individual patients.

(JAMA. 1993;270:1233-1241)

Author Affiliations
From the ICU Research Unit, George Washington University Medical Center, Washington, DC (Drs Knaus and Wagner); Division of Biometry, Duke University Medical Center, Durham, NC (Dr Harrell); Critical Care Research Unit, The Cleveland (Ohio) Clinic Foundation (Dr Fisher); Brown University, Providence, RI (Dr Opal); Walter Reed Army Institute of Research, Washington, DC (Dr Sadoff); APACHE Medical Systems Inc, Washington, DC (Ms Draper); and Center for Pharmacoepidemiology Research, State University of New York at Buffalo (Mss Walawander and Conboy and Dr Grasela).

Footnotes
Drs Knaus and Wagner are founders and shareholders in APACHE Medical Systems Inc. Ms Draper is an employee of APACHE Medical Systems Inc. Dr Harrell is a consultant to APACHE Medical Systems Inc. Drs Fisher, Opal, and Sadoff are on the Physician's Advisory Committee for Synergen Inc, Boulder, Colo.

Reprint requests to ICU Research Unit, George Washington University Medical Center, 2300 K St NW, Washington, DC 20037 (Dr Knaus).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

The Effects of Generalized Joint Laxity on Risk of Anterior Cruciate Ligament Injury in Young Female Athletes
Myer et al.
Am J Sports Med 2008;36:1073-1080.
ABSTRACT | FULL TEXT  

Quantifying Risk and Benchmarking Performance in the Adult Intensive Care Unit
Higgins
J Intensive Care Med 2007;22:141-156.
ABSTRACT  

Determinants of Mortality in Patients with Severe Sepsis
Johnston
Med Decis Making 2005;25:374-386.
ABSTRACT  

Septic Shock of Early or Late Onset: Does It Matter?
Roman-Marchant et al.
Chest 2004;126:173-178.
ABSTRACT | FULL TEXT  

Current Epidemiology of Septic Shock: The CUB-Rea Network
Annane et al.
Am. J. Respir. Crit. Care Med. 2003;168:165-172.
ABSTRACT | FULL TEXT  

Influence of Systemic Inflammatory Response Syndrome and Sepsis on Outcome of Critically Ill Infected Patients
Alberti et al.
Am. J. Respir. Crit. Care Med. 2003;168:77-84.
ABSTRACT | FULL TEXT  

Is Pneumonia Still the Old Man's Friend?--Reply
Angus
Arch Intern Med 2003;163:1492-1492.
FULL TEXT  

A 3-Level Prognostic Classification in Septic Shock Based on Cortisol Levels and Cortisol Response to Corticotropin
Annane et al.
JAMA 2000;283:1038-1045.
ABSTRACT | FULL TEXT  

Impact of Immunomodulating Therapy on Morbidity in Patients with Severe Sepsis
PITTET et al.
Am. J. Respir. Crit. Care Med. 1999;160:852-857.
ABSTRACT | FULL TEXT  

Postoperative Nomogram for Disease Recurrence After Radical Prostatectomy for Prostate Cancer
Kattan et al.
JCO 1999;17:1499-1499.
ABSTRACT | FULL TEXT  

Relationship of Systemic Inflammatory Response Syndrome to Organ Dysfunction, Length of Stay, and Mortality in Critical Surgical Illness: Effect of Intensive Care Unit Resuscitation
Talmor et al.
Arch Surg 1999;134:81-87.
ABSTRACT | FULL TEXT  

Multivariate Analysis of 9 Disease-Associated Variables for Outcome Prediction in Patients With Sepsis
Calvano et al.
Arch Surg 1998;133:1347-1350.
ABSTRACT | FULL TEXT  

Epidemiology of Sepsis Syndrome in 8 Academic Medical Centers
Sands et al.
JAMA 1997;278:234-240.
ABSTRACT  

p55 Tumor Necrosis Factor Receptor Fusion Protein in the Treatment of Patients With Severe Sepsis and Septic Shock: A Randomized Controlled Multicenter Trial
Abraham et al.
JAMA 1997;277:1531-1538.
ABSTRACT  

Does HIV status influence the outcome of patients admitted to a surgical intensive care unit? A prospective double blind study
Bhagwanjee et al.
BMJ 1997;314:1077-1077.
ABSTRACT | FULL TEXT  

Magnitude and Duration of the Effect of Sepsis on Survival
Quartin et al.
JAMA 1997;277:1058-1063.
ABSTRACT  

Treatment of Severe Systemic Inflammatory Response Syndrome and Sepsis With a Novel Bradykinin Antagonist, Deltibant (CP-0127) Results of a Randomized, Double-blind, Placebo-Controlled Trial
Fein et al.
JAMA 1997;277:482-487.
ABSTRACT  

Incidence, Risk Factors, and Outcome of Severe Sepsis and Septic Shock in Adults: A Multicenter Prospective Study in Intensive Care Units
Brun-Buisson et al.
JAMA 1995;274:968-974.
ABSTRACT  

Blocking interleukin-1 in sepsis
Dinarello
Innate Immunity 1995;2:157-162.
ABSTRACT  

Risk assessment in recent clinical trials in sepsis/SIRS: lessons learned and future directions
Knaus et al.
Innate Immunity 1995;2:169-175.
ABSTRACT  

Customized Probability Models for Early Severe Sepsis in Adult Intensive Care Patients
Gall et al.
JAMA 1995;273:644-650.
ABSTRACT  

Defining Sepsis
Knaus et al.
JAMA 1994;272:1901-1901.
ABSTRACT  

Defining Sepsis-Reply
Abraham and Raffin
JAMA 1994;272:1901-1901.
ABSTRACT  

The French National Registry of HA-1A (Centoxin) in Septic Shock: A Cohort Study of 600 Patients
The National Committee for the Evaluation of Cento
Arch Intern Med 1994;154:2484-2491.
ABSTRACT  

Modeling the Severity of Illness of ICU Patients: A Systems Update
Lemeshow and Jean-Roger Le
JAMA 1994;272:1049-1055.
ABSTRACT  

Recombinant Human Interleukin 1 Receptor Antagonist in the Treatment of Patients With Sepsis Syndrome: Results From a Randomized, Double-blind, Placebo-Controlled Trial
Fisher et al.
JAMA 1994;271:1836-1843.
ABSTRACT  

Sepsis Therapy Trials: Continued Disappointment or Reason for Hope?
Abraham and Raffin
JAMA 1994;271:1876-1878.
ABSTRACT