Non-inferiority clinical trials: importance and applications in health sciences

Abstract

Non-inferiority randomized clinical trials are indicated when it is intended to prove that an experimental group is not inferior to a control group by more than a margin of non-inferiority. However, this type of study differs from traditional randomized clinical trials (superiority studies) because they have particularities that impact on the formulation of hypothesis to be tested, experimental design (noninferiority margin determination, adapted sample size calculation, sensitivity of the study and data final analysis) and also on the presentation of data when writing the manuscript. Therefore, this article aims to present and discuss the particularities of non-inferiority clinical studies, since these requirements are fundamental to guarantee the validity of the conclusions of this type of study.

Comparison of the timed inspiratory effort index with the T-piece trial as a decision-making tool for extubation: a randomized controlled non-inferiority trial

“…In the present study, we chose to use the TIE index (taking into consideration its higher predictive value - AUC >0.90) ( 7 - 10 , 15 , 16 ) as an extubation decision tool and compared its performance with that of the traditional T-piece spontaneous breathing trial. Given the impossibility of using a placebo group, the non-inferiority trial was chosen to compare this new strategy that completed in one or fewer minutes with the standard intervention that takes 30 min or more to perform ( 20 ).…”

“…We calculated that a sample of 80 subjects per group would provide the trial with 80% power to detect non-inferiority of the primary outcome at an alpha of 0.05 and a non-inferiority margin of 15 percentage points, assuming a dropout rate of 10%, and that ∼80% of the subjects in the TIE index group and the T-piece trial group would have successful weaning ( 19 , 20 ).…”

Biosimilars: A Comparative Study of Regulatory, Safety and Pharmacovigilance Monograph in the Developed and Developing Economies

“…Defining delta is thus the most challenging in noninferiority trials (104). Generally, non-inferiority margin is selected based on statistical and clinical considerations (such as increased safety, better compliance, easy administration, convenient dosing schedule, and low costs); but regulatory authorities (such as EMA and US-FDA) preference is to set historical evidence of the active control as standard for defining delta (104,105). FDA expects at least two adequate and well-controlled non-inferiority trials to support biosimilarity; but in certain cases, such as where non-inferiority trials show superiority to an active control, a single trial may be taken as sufficient basis to support effectiveness of the test drug (106).…”