Understanding noninferiority trials

Abstract

Noninferiority trials test whether a new experimental treatment is not unacceptably less efficacious than an active control treatment already in use. With continuous improvements in health technologies, standard care, and clinical outcomes, the incremental benefits of newly developed treatments may be only marginal over existing treatments. Sometimes assigning patients to a placebo is unethical. In such circumstances, there has been increasing emphasis on the use of noninferiority trial designs. Noninferiority trials are more complex to design, conduct, and interpret than typical superiority trials. This paper reviews the concept of noninferiority trials and discusses some important issues related to them.

Keywords: Clinical trials; Controlled clinical trials; Noninferiority trial; Randomized controlled clinical trials.

Figures

Fig. 1

Testing superiority, equivalence/noninferiority. Δ: margin for equivalence/noninferiority.

Fig. 2

Noninferiority margin. The positioning of the outcome result for each treatment is indicated. Δ: margin for equivalence/noninferiority.

Fig. 3

Hypothetical scenario. Numbers represent the values of a positive outcome. The noninferiority margin is determined by halving the control effect, based on a historical placebo-controlled trial. The upper limit of the 95% confidence interval (CI) for the treatment difference by the new treatment compared to the control is less than the margin to conclude noninferiority, although there is an implication of incomparability. Δ: margin for equivalence/noninferiority.