Analysis Sets and Inference in Clinical Trials

The debate about what constitutes a valid analysis of clinical trial data is longstanding. While the intention-to-treat (ITT) principle seems to be widely accepted in the context of controlled clinical trials aiming to show superiority of an experimental treatment over a control, the best choice for a noninferiority trial is still under discussion. In this article, it is argued that the definition of analysis sets and the purpose of ITT and per-protocol analyses proposed in the International Conference on Harmonisation biostatistics guideline E9 should be revised to allow for more appropriate analyses, given that statistical methodology has been developed since the guideline was issued.