The non-inferiority design is widely used in clinical trials of generic drugs. 6 years after this initial draft was made available for public, FDA released final guidance on the development of such studies on 07 Nov 2016.
The successful non-inferiority trial is intended to show that the difference between the new drug and the active control is small enough to extrapolate to the new drug all the experience of the active control clinical use. The new drug is then marketed based on conclusions made about active control drug effectiveness some time ago in other trials. The regulator is concerned that for various reasons all these former conclusions might become proven wrong when new is marketed. Per the assay sensitivity principle, the Agency expects that effectiveness of active control will be shown in every non-inferiority trial. If this is principle is not met, FDA will consider a trial as not valid even if the non-inferiority hypothesis is proven.
Main statistical and planning issues, as well as differences between superiority trial and non-inferiority trial, are also discussed in the Guidance.
It is stated that non-inferiority margin should not be greater than actual treatment effect of an active control, and those study endpoints should be based on proper sensitivity relative to the effect of the drugs, and sensitivity itself should be chosen with regards to historical data.
Proper historical data reporting and interpretation are also discussed in the document.
Furthermore, FDA gives some examples of correct and incorrect non-inferiority trial development and includes the FAQ section into the document.
Guidance is available at the following link: http://www.fda.gov/downloads/Drugs/…/Guidances/UCM202140.pdf