BACKGROUND

A complex network of biological mediators underlies the clinical syndrome of sepsis. The nonspecific physiologic criteria of sepsis syndrome or the systemic inflammatory response syndrome do not adequately identify patients who might benefit from either conventional anti-infective therapies or from novel therapies that target specific mediators of sepsis. Validated biomarkers of sepsis may improve diagnosis and therapeutic decision making for these high-risk patients.

OBJECTIVES

To develop a methodologic framework for the identification and validation of biomarkers of sepsis.

METHODS

A small group meeting of experts in clinical epidemiology, biomarker development, and sepsis clinical trials; selective narrative review of the biomarker literature.

RESULTS

The utility of a biomarker is a function of the degree to which it adds value to the available clinical information in the domains of screening, diagnosis, risk stratification, and monitoring of the response to therapy. We identified needs for greater standardization of biomarker methodologies, greater methodologic rigor in biomarker studies, wider integration of biomarkers into clinical studies (in particular, early phase studies), and increased collaboration among investigators, pharmaceutical industry, biomarker industry, and regulatory agencies.

CONCLUSIONS

Biomarkers promise to transform sepsis from a physiologic syndrome to a group of distinct biochemical disorders. This transformation could aid therapeutic decision making, and hence improve the prognosis for patients with sepsis, but will require an unprecedented degree of systematic investigation and collaboration.