Ng T.-H. Noninferiority testing in clinical trials: issues and challenges

Boca Raton: Taylor & Francis/CRC Press, 2015. - 206p.Reflecting the vast research on noninferiority (NI) designs from the past 15 years, Noninferiority Testing in Clinical Trials: Issues and Challenges explains how to choose the NI margin as a small fraction of the therapeutic effect of the active control in a clinical trial. Requiring no prior knowledge of NI testing, the book is easily accessible to both statisticians and nonstatisticians involved in drug development.
With over 20 years of experience in this area, the author introduces the basic elements of the NI trials one at a time in a logical order. He discusses issues with estimating the effect size based on historical placebo control trials of the active control. The book covers fundamental concepts related to NI trials, such as assay sensitivity, constancy assumption, discounting, and preservation. It also describes patient populations, three-arm trials, and the equivalence of three or more groups.FeaturesFocuses on the rationale for selecting the NI margin as a small fraction of the therapeutic effect of the active control in a clinical trial.
Uses the same notations for treatment groups for various types of data, such as continuous, survival, and binary.
Presents a divide-and-conquer strategy for choosing the NI margin and discounting.
Offers clear explanations of two different concepts: preservation and discounting.
Explains the differences between fixed-margin and synthesis methods.
Addresses the issues of switching between superiority and noninferiority.
Discusses gold-standard design and the equivalency of three or more treatment groups.
Includes an entire chapter on intention-to-treat and per-protocol analyses.
Applies the concepts to an extended example of thrombolytic therapies.