Noninferiority Margin and Other Methodological Issues in Designing Noninferiority Trials: A Review

Abstract

Noninferiority clinical trials help in detecting a new treatment that have roughly the same effectiveness, yet may offer different advantages. Thus, noninferiority trials can be used in a situation when a new treatment has almost the same effectiveness as its comparator but may offer other advantages over the existing drug such as a novel method of administration or a better safety profile. Some argue that noninferiority trials only benefit pharmaceutical companies as they permit medicines without any added effectiveness to get marketing authorization. There are many basic differences between noninferiority and superiority trials. Noninferiority clinical trials aim to prove that the test product is not unreasonably inferior, or “noninferior” than the comparator by more than a prestipulated margin. From a methodological perspective, compared to superiority trials, noninferiority trials have methodological issues in design and analysis that can influence proper inference and also noninferiority trials are a source of great dispute. One of the pivotal but arduous steps in planning noninferiority trial is itemizing a noninferiority margin: a prelude below which it can be accepted that the experimental drug is not worse than its comparator.

Noninferiority trials in oral medicine

“…The target may also be to prevent or overcome antimicrobial resistance, reduce adverse effects, or allow an easier scheme of administration. NI trials have been criticized as a strategy to benefit pharmaceutical companies interested in commercializing medicines with no advantages in effectiveness (Gupta, ). In spite of this argument, the increasing use of this sort of trial in many clinical areas has been acknowledged as a marker of its growing importance in the health sciences (Wangge, Roes, de Boer, Hoes, & Knol, ).…”