Objectives

• Review state of current biomarkers and surrogate endpoints in sepsis clinical research
  • What is the experience to date in clinical trials with specific biomarkers and secondary endpoints?
  • What is the association of biomarkers and surrogate endpoints with mortality or organ failure?
  • How do physiologic endpoints (e.g., reversal of shock, development of organ failure) interact with biomarkers and mortality?
  • Have these physiologic endpoints been affected by the experimental therapies?
• Discuss role of biomarkers and surrogate endpoints in enhancing development of trials of novel therapies for septic shock and review their role in preclinical and clinical studies in measuring therapeutic and adverse effects of agents
  • Can substitution of biomarkers for clinical endpoints be used to evaluate the safety and efficacy of a novel therapy?
  • What is necessary to validate biomarkers in preclinical and clinical studies?
  • Can information be obtained from existing databases of completed trials to validate biomarkers?
  • Will trial design be improved with novel endpoints?
  • Can biomarkers be applied as a surrogate endpoints in Phase III trials of therapies for sepsis?
• Discuss how novel technologies may contribute to the development of biomarkers and facilitate the identification of target populations
  • What strategies are necessary to incorporate novel technologies (e.g., functional and structural imaging, patterns of gene expression via cDNA microarray technology, gene polymorphisms, cell signaling markers, circulating biomarkers, functional assays such as proinflammatory activity of body fluids, banked tissues from clinical trials) in the development of novel biomarkers?
  • How should the new technologies be validated in preclinical and clinical applications?
  • What resources are available to fund biomarker research, including new technology application, development of tissue and blood banks from clinical trials, and consortium development?

Agenda

Panel Discussion I

Overview of Biomarkers and Secondary Endpoints in Sepsis
Anthony F. Suffredini, M.D.

IL-6 and Tumor Necrosis Factor Levels as Markers of Response in Sepsis Trials
Edward Abraham, M.D., University of Colorado Health Sciences Center

Cytokine Balance in Acute Respiratory Distress Syndrome: Implications for Detecting Acute Lung Injury
Thomas R. Martin, M.D.

Nonmortal Clinical Endpoints for Trials in Critically Ill Patients
Gordon Bernard, M.D., Vanderbilt University Medical Center

Panel Discussion II

Prospects for Functional Immune Assessment in Severe Infections and Septic Shock
Stephen F. Lowry, M.D., Robert Wood Johnson Medical School

Validating Biomarkers and Ascertaining Their Relationship to Clinical Endpoints
Polly E. Parsons, M.D., University of Colorado Health Sciences Center

Severity of Infectious Challenge Alters the Effects of Anti-Inflammatory Agents in Sepsis
Peter Q. Eichacker, M.D., National Institutes of Health Clinical Center

cDNA Microarray Applications in Critical Care Medicine
Robert L. Danner, M.D., National Institutes of Health Clinical Center

Summary of Recommendations

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