Choosing a Noninferiority Margin for NI Trials in Infectious Disease Therapeutic Area

• Activity Number: 355
• Type: Contributed
• Date/Time: Tuesday, August 6, 2013 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Jing Zhao*+ and Seth Thompson
• Companies: BMS and Merck
• Keywords: Non-inferiority Trial ; NI margin ; effect size ; fixed-margin approach

Abstract

Noninferiority trials are intended to show that the effect of a new treatment is not worse than that of an active control by more than a specified margin. The usual reason for using a non-inferiority active control study design instead of a superiority is an ethical one. Specifically, this design is chosen when it would not be ethical to use a placebo, because the disease is life-threatening or there is an effective treatment available to patients (i.e. HIV/AIDS, Invasive Aspergillosis). Determining the Non-inferiority margin is the single greatest challenge in the design, conduct, and interpretation of NI trials. Two components are needed to define a NI margin: 1) the effect size of the active control used in the NI trial; and 2) the largest loss of the active control's effect that would be clinically acceptable. One of the specific difficulties to Infectious Disease (ID) area is that the historical effect size of the active control is hard to obtain as there were no available historical placebo-control trials to use. A method similar to Fixed Margin approach is proposed to accommodate such a situation in order to make a reasonable and clinical acceptable NI design.