Table 2 Reasons for lack of survival improvements in sepsis clinical trials

• Declining mortality rates over time

• Over-estimated treatment effects

• Suboptimal pre-clinical models

• Knowledge of pathophysiology is still evolving, making pathophysiologic targets difficult to identify

• Incorrect treatment targets

• Heterogeneity of the syndrome

• Heterogeneity of the patient population

• Improbability that a single treatment can impact key pathophysiologic processes that influence all-cause mortality