This document provides guidance to sponsors and applicants submitting investigational drug applications (INDs), new drug applications (NDAs), biologics licensing applications (BLAs), or supplemental applications on the appropriate use of non-inferiority (NI) study designs to provide evidence of the effectiveness of a drug or biologic, usually because a superiority study design (drug versus placebo, dose response, or superiority to an active drug) cannot be used. The guidance gives advice on when NI studies intended to demonstrate effectiveness of an investigational drug can provide interpretable results, how to choose the NI margin, and how to test the NI hypothesis.

This guidance does not provide recommendations for the use of NI study designs to evaluate the safety of a drug.

In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidance documents describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in FDA guidance documents means suggested or recommended, but not required.

This guidance finalizes the draft guidance for industry, Non-Inferiority Clinical Trials, published in 2010. In addition, it supersedes the guidance for industry, Antibacterial Drug Products: Use of Noninferiority Trials to Support Approval, also published in 2010, which will be withdrawn.

Posted on the FDA website on 7 November 2016