Choosing an equivalence limit for noninferiority or equivalence studies.

Studies that compare treatments with the purpose of demonstrating that the treatments are similar require an a priori definition of an equivalence limit, how different the treatments can be before the difference is of concern. Defining such an equivalence limit is one of the most difficult aspects of planning the study. Three principles are proposed for setting such limits, depending on the objective of the study: a putative placebo calculation, an approach based on clinically important differences, and methods based on statistical properties. All methods will be useful for many studies, but the study objective should determine the final choice of an equivalence limit. The statistician must play an integral role in determining the final equivalence limit. Advice is offered for helping the statistician participate in the decision on the equivalence limits.