Should non-inferiority drug trials be banned altogether?

Non-inferiority (NI) trials can be used in a situation when a new drug is expected to have a similar efficacy to its comparator but can offer other advantages over the existing drug, such as a more convenient method of administration or fewer side effects. Here, we discuss the advantages and disadvantages of NI trials from an ethical, methodological and regulatory perspective. We suggest that such trials should be designed to address simultaneously the objective of showing NI with regard to drug efficacy and the objective of establishing superiority of the additional advantages of a drug over its active comparator.

► Non-inferiority trials are designed to show a new drug is not worse than an active comparator.
► These trials have ethical, methodological and regulatory challenges.
► They should be designed to simultaneously have a non-inferiority efficacy aim and superiority aim(s) of its additional advantages.