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Risk assessment in recent clinical trials in sepsis/SIRS: lessons learned and future directions

The ICU Research Unit, Department of Anesthesiology, The George Washington University, Washington DC, The Division of Biometry and The Heart Center, Duke University Medical Center, Durham, North Carolina, APACHE Medical Systems, Inc., McLean, Virginia, USA

D.P. Wagner

The ICU Research Unit, Department of Anesthesiology, The George Washington University, Washington DC, The Division of Biometry and The Heart Center, Duke University Medical Center, Durham, North Carolina, APACHE Medical Systems, Inc., McLean, Virginia, USA

X. Sun

The ICU Research Unit, Department of Anesthesiology, The George Washington University, Washington DC, The Division of Biometry and The Heart Center, Duke University Medical Center, Durham, North Carolina, APACHE Medical Systems, Inc., McLean, Virginia, USA

F.E. Harrell, JR

The ICU Research Unit, Department of Anesthesiology, The George Washington University, Washington DC, The Division of Biometry and The Heart Center, Duke University Medical Center, Durham, North Carolina, APACHE Medical Systems, Inc., McLean, Virginia, USA

J.S. Hedstrom

The ICU Research Unit, Department of Anesthesiology, The George Washington University, Washington DC, The Division of Biometry and The Heart Center, Duke University Medical Center, Durham, North Carolina, APACHE Medical Systems, Inc., McLean, Virginia, USA

This presentation reviews recent evidence that the design and analysis of clinical trials in sepsis could be improved by using individualized sepsis specific risk assessments. These individual patient risk profiles are derived from independent databases. They describe patients on a continuum of risk. They have correlated very closely to mortality outcomes in recent clinical trials. These individual risk assessments can improve the interpretation of trial data by controlling for potentially confounding patient risk factors, thereby permitting the signal or impact from novel therapy to be more precisely determined.

When these individual risk assessments are combined with data on the degree of the host's specific inflammatory response they may eventually lead to the development of specific patient profiles to describe where immunotherapy is appropriate and other situations where it may either not be indicated or pose a risk. This relationship needs further investigation, however, before it can be confirmed.

Changes in the acute physiology score can also hold substantial promise as an alternative endpoint for clinical trials. Therapies which significantly and consistently reduce the APS during the initial days of sepsis in small, early exploratory Phase I and II trials may be excellent candidates for investigation in larger Phase III studies.

Journal of Endotoxin Research, Vol. 2, No. 3, 169-175 (1995)
DOI: 10.1177/096805199500200305


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