Key insights and challeneges in noninferiority trials

Abstract

Noninferiority clinical trials are crucial for evaluating the effectiveness of new interventions compared to standard interventions. By establishing statistical and clinical comparability, these trials can be conducted to demonstrate that a new intervention is not significantly inferior to the standard intervention. However, selecting appropriate noninferiority margins and study designs are essential to ensuring valid and reliable results. Moreover, employing the Consolidated Standards of Reporting Trials (CONSORT) statement for reporting noninferiority clinical trials enhances the quality and transparency of research findings. This article addresses key considerations and challenges faced by investigators in planning, conducting, and interpreting the results of noninferiority clinical trials.

Keywords: Bias; Clinical trial; Noninferiority; Randomized controlled trial; Research design; Sample size; Treatment outcome..

Fig. 1.

Example of a forest plot for a noninferiority test. The black circle indicates the representative value of the difference between the two treatments, and the corresponding whiskers indicate the estimated two-sided CI. Note that the noninferiority margin (M, red line) is not a value of 0. A and B are inconclusive because the CI includes M, even though a significant difference exists between the treatments. C represents a noninferior conclusion because the CI is located below M but is also inferior in the sense of superiority. D represents an inferior conclusion because the CI is located above M. E represents superiority to the experimental treatment because the CI is located below zero. F represents a noninferior conclusion because the CI is located below M. G is inconclusive because the CI includes M, even if no significant difference exists between the treatments.

Fig. 2.

Online sample size calculation for a continuous outcome noninferiority clinical trial. This figure was reproduced from Sealed Envelope Ltd., 2012 with permission [16].