Book: Ng, T-H. (2014). Noninferiority Testing in Clinical Trials: Issues and Challenges. Boca Raton, FL: Chapman & Hall/CRC (http://www.crcpress.com/product/isbn/9781466561496) |
The objective of a noninferiority (NI) trial is to show that the test treatment or the experimental treatment is not inferior to the standard therapy or the active control by a small margin known as the NI margin. This tutorial elaborates the rationale of choosing the NI margin as a small fraction of the therapeutic effect of the active control as compared to placebo in testing of the NI hypothesis of the mean difference with a continuous outcome. This NI margin is closely related to M1 and M2, the NI margins discussed in the FDA draft guidance on NI clinical trials issued in March of 2010.
This tutorial also covers fundamental concepts related to NI trials, such as assay sensitivity, constancy assumption, discounting and preservation. As time permits, this tutorial (i) explains the differences between fixed-margin and synthesis methods, (ii) addresses the issues of switching between superiority and noninferiority, (iii) discusses gold-standard design and the equivalency of three or more treatment groups, (iv) investigates the roles of intention-to-treat and per-protocol analyses, and (v) presents an extended example of thrombolytic therapies.
Tie-Hua Ng, Ph.D. (Statistics from the University of Iowa in 1980) held several positions before joining the Food and Drug Administration (FDA) in 1987. He left the FDA in 1990 to work for the Henry M. Jackson Foundation. In 1995, he returned to the FDA, Center for Biologics Evaluation and Research (CBER). He is currently a team leader supporting the Office of Blood Research and Review within CBER. Over the past 23 years, he had made numerous presentations at professional meetings and published extensively in the area of active controlled/noninferiority studies. He offered four half-day short courses from 2009 through 2012. As a result of these efforts, he is the sole author of a book entitled “Noninferiority Testing in Clinical Trials: Issues and Challenges” published in December 2014.