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March 8, 2006

Lessons From and Cautions About Noninferiority and Equivalence Randomized Trials

Author Affiliations

Author Affiliation: Nordic Cochrane Centre, Copenhagen, Denmark.

JAMA. 2006;295(10):1172-1174. doi:10.1001/jama.295.10.1172

The design of the classic, parallel-group randomized trial involves formulating a null hypothesis of no difference between 2 interventions and identifying a clinically relevant difference (Δ) that researchers do not wish to overlook. Commonly referred to as superiority trials, the investigators usually hope to be able to reject the null hypothesis and demonstrate a difference between interventions. In contrast, a noninferiority trial is one-sided in nature1 as it seeks to determine whether a new intervention is no worse than a reference intervention within a prespecified noninferiority interval (−Δ to 0) for the primary outcome. Similarly, an equivalence trial aims to determine whether 2 interventions have a similar effect, within a prespecified interval (−Δ to + Δ).