A clinician's guide to the assessment and interpretation of noninferiority trials for novel therapies.

A noninferiority trial is designed to demonstrate that an experimental therapy is not worse than an active control. Although noninferiority trials are superficially similar to conventional superiority trials, there are fundamental differences. In particular, aspects of a study that make the therapies appear more similar than they actually are can falsely bias the study toward demonstrating noninferiority. This has important implications for methodologic techniques such as blinding and statistical analysis based on the intention-to-treat principle. When applying the results of noninferiority trials, clinicians should be judicious in determining whether the degree of noninferiority demonstrated is clinically acceptable and whether the ancillary benefits of the treatment justify its use.