A comparison of intent-to-treat and per-protocol results in antibiotic non-inferiority trials.

While the intent-to-treat (ITT) analysis is widely accepted for superiority trials, there remains debate about its role in non-inferiority trials. It is often said that the ITT tends to be anti-conservative in the demonstration of non-inferiority. This concern has led to some reliance on per-protocol (PP) analyses that exclude patients on the basis of post-baseline events, despite the inherent bias of such analyses. We compare ITT and PP results from antibiotic trials presented to the public at the FDA's Anti-infective Drug Advisory Committee from 1999 to 2003. While the number of available trials is too small to produce clear conclusions, these data did not support the assumption that the ITT would lead to smaller treatment difference than the PP, in the setting of antibiotic trials. Possible explanations are discussed. 2004 by John Wiley & Sons, Ltd.