Noninferiority Trial Design: Opportunities and Challenges

Abstract

Defining treatment effectiveness is the foundation of evidence-based practice. Most studies comparing the effectiveness of treatment options involve superiority designs in which a treatment is compared against a placebo, standard care, or an alternative treatment. However, in scenarios in which it is not ethical to consider these options, noninferiority designs can be considered. Noninferiority (NI) trials aim to demonstrate that a new treatment is not unacceptably worse than a standard treatment. Noninferiority is determined relative to a noninferiority margin, which is the difference between the test and active control treatment that is not unacceptably clinically inferior. However, there are important considerations with respect to the design, analysis, and interpretation of NI studies, which differ from superiority trials. This review will outline the key components of NI trials, how to interpret the findings, and understand their nuances and potential limitations.

Keywords: Clinical trial; noninferiority; noninferiority margin.