Relative risk (RR) and 95% confidence intervals (95% CI) for 28-day mortality in each study. RR is plotted on the natural logarithm scale. n/N = number of deaths at 28 days divided by the total number of patients randomly assigned to drotrecogin alfa (activated) or placebo. For the phase II trial, only patients who were randomized to the same dose and duration of drotrecogin alfa (activated) used in the Recombinant Human Activated Protein C Worldwide Evaluation of Severe Sepsis (PROWESS) and Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) trials are included [37].

Effect of drotrecogin alfa (activated) on 28-day mortality. Results are classified by low-risk and high-risk subgroups from the Recombinant Human Activated Protein C Worldwide Evaluation of Severe Sepsis (PROWESS) and Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) trials, defined by either Acute Physiology and Chronic Health Evaluation (APACHE II) score (less than 25, and 25 or more) or organ failure (single and multiple). Weight refers to the contribution of each study to the overall pooled estimate of treatment effect for each low-risk and high-risk subgroup. The weight of each study is calculated as the inverse of the variance of the natural logarithm of its relative risk. Each summary relative risk (RR) is plotted on the natural logarithm scale. The size of the symbol denoting each point estimate approximates the weighting of each study to each pooled effect measure. Each pooled effect measure is calculated with the use of a random-effects model. n/N = number of deaths at 28 days divided by the total number of patients in each particular subgroup randomly assigned to drotrecogin alfa (activated) or placebo. The numbers of patients and deaths at 28 days in each subgroup were estimated from data provided in references [2], [4] and [11] for the PROWESS trial, and in references [5] and [12] for the ADDRESS trial.