Study designs of evaluations included in the review
Phase III or equivalent randomised controlled trials (RCTs) that were placebo-controlled and double-blind were eligible for inclusion. Eligible studies had adequate power (>80%) to detect statistically significant differences at the 0.05 level (two- sided alpha). Studies with multiple active therapy arms were required to adjust for multiple comparisons. Prospective definition of appropriate correction for repeated comparisons at planned interim analyses was also required.
Specific interventions included in the review
Studies of any intervention compared with placebo for the treatment of severe sepsis were eligible for inclusion. The included studies used the following interventions: platelet activating factor hydrolase, tissue factor pathway inhibitor, hydrocortisone plus fludrocortisone, antithrombin III, ibuprofen, IL-1ra, antiendotoxin antibodies (E5 or HA-1A), p55 TNF receptor fusion protein, anti-TNF antibodies (MAK195F, BAYx1351 or afelimomab), activated protein C, platelet activating factor receptor antagonist, anti-Enterobacteriaceae common antigen antibody, and the granulocyte colony stimulating factor filgrastim.
Participants included in the review
Studies of adult patients diagnosed with sepsis, severe sepsis or septic shock were eligible for inclusion. The included studies were of patients with known or suspected infection, evidence of a systemic response to infection, and one or more organ dysfunctions resulting from the systemic response. The participants in the selected studies were grouped according to illness severity. The following criteria were used to define these subgroups: Simplified Acute Physiology Score, APACHE II, presence or absence of shock, presence or absence of hypotension, presence or absence of acute respiratory distress syndrome, IL-6 concentration, cardiovascular Sepsis-related Organ Failure Assessment score, and the presence of single or multiple organ failures.
Outcomes assessed in the review
The primary outcome assessed was 28- to 30-day all-cause mortality, with a prospectively-defined end point of a statistically significant reduction in 28-day all-cause mortality. All included studies assessed 28-day mortality, except one which assessed 29-day mortality. The results of safety assessments were also included in the review.
How were decisions on the relevance of primary studies made?
The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.