Non-inferiority study

A non-inferiority study describes a study where the aim is to show that the effectiveness of one technology is not inferior to a comparator technology by a clinically important amount. This non-inferiority margin (M2: also called the ‘preserved fraction’ or ‘degree of inferiority’) is the percentage of the effect size of the current or comparator technology against a placebo comparator (M1) that is clinically acceptable to be maintained for non-inferiority to be assumed. M1 and M2 need to be established before a study, to allow a sample size to be calculated with sufficient power to support a conclusion that the intervention technology is non-inferior or equivalent to the comparator. Particular attention needs to be paid to the derivation of M1 and M2, and the quality of the study design and execution. Unlike for superiority studies, intention-to-treat analyses are unlikely to be conservative (per protocol analyses may need to be performed), and statistical hypothesis testing may need to be one-sided at the 2.5% level. Non-inferiority and clinical equivalence studies have become more common in recent years for interventions where placebo comparators cannot be used for ethical reasons, or where there is interest by healthcare payers in establishing comparative effectiveness of a new technology. While non-inferiority studies are similar to clinical equivalence studies in rationale and design, it is important to note that they are distinct concepts.