CANCELLED: Impact of the Noninferiority Clinical Trials Draft FDA Guidance on Noninferiority Margins Interpretation

• Activity Number: 192
• Type: Roundtables
• Date/Time: Monday, August 1, 2011 : 12:30 PM to 1:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Claude Petit
• Companies: Boehringer Ingelheim
• Keywords: non inferiority ; guidance ; sample size

Abstract

In March 2010, the FDA has issued this guidance for comments.This guidance introduces the M1 and M2 non inferiority margin definitions and compares the 95-95 fixed margin method to the synthesis method. M1 is defined as the entire effect of the active control assumed to be present in the NI study and M2 as the largest clinically acceptable difference of the test drug compared to the active control. Ruling out a difference between the active control and test drug larger than M1 is the critical finding that supports a conclusion of effectiveness (small p-value requestd). However, as M2 represents a clinical judgment, there may be a greater flexibility in interpreting a 95% upper bound for C-T that is slightly greater than M2, as long as the upper bound is still well less than M1. The objective of the roundtable is to investigate whether this guidance has changed the current statistical practise related to sample size calculation and the way to interpret NI clinical trials.