Preservation of effect and the regulatory approval of new treatments on the basis of non-inferiority trials

The criteria for approval of an experimental treatment on the basis of active-controlled non-inferiority trials often include demonstration of 'preservation of effect' relative to the active control. While this appears on its surface to be a reasonable criterion, on closer inspection it can be shown to lead to serious logical inconsistencies. In particular, an experimental treatment may have clinical trial results that are superior to those for the standard treatment and yet fail to meet this criterion for approval. In this paper we propose a set of principles that will help avoid these logical inconsistencies, and we argue that the qualities of an experimental treatment that are required for approval should be consistent regardless of the presence or absence of existing treatments and the type of study design used to evaluate the treatment. Copyright (C) 2007 John Wiley & Sons, Ltd.