Design and conduct of clinical trials: development of a clinical study based on animal data

There are numerous animal research studies documenting the effectiveness of corticosteroid and antibiotic therapy in E. coli-induced shock. Findings from other reports show equally effective treatment of shock induced by endotoxin, using corticosteroid without antibiotics. Early treatment using pharmacologic doses of corticosteroid is very effective in several species of animals in preventing or ameliorating the pathophysiologic changes induced by E. coli or endotoxin, and enhancing the probability of permanent survival (more than 7 days). This form of treatment given acutely (first 12 hours) produces no observable detrimental effects in animal models. It was considered of extreme importance to determine if this particular therapy had successful human application. Results from previous clinical studies evaluating the effectiveness of corticosteroid in severe sepsis/septic shock were in marked conflict. We accepted the challenge to design a clinical study to determine if there were human subgroup populations with severe sepsis who responded similarly to the animal treated with corticosteroid.