Active-control clinical trials to establish equivalence or noninferiority: methodological and statistical concepts linked to quality.

The randomized, double-blind, placebo-controlled trial is the optimum method for clinical evaluation of new treatments, as assessed by clinicians and statisticians. However, if a known standard of therapy exists, it may be difficult to prove that a new therapy is superior. Equivalence and noninferiority clinical trial designs are now frequently utilized in clinical medical research. This article reviews the statistical differences between superiority, equivalence, and noninferiority design schemes, which pose specific ethical questions and have important implications for interpretation and clinical application of trial results. A guideline is proposed as a standard approach for reporting to facilitate qualitative assessment of the methodology of these trials.