Some Thoughts on Challenges for Noninferiority Study Designs

New interventions that may have some advantage over standard treatments by being less invasive, less toxic, or less costly are often compared to standard therapy. Noninferiority trials aim to demonstrate that the new intervention is almost as good as, or even better than, the standard. A commonly used paradigm makes numerous assumptions to obtain a statistical and clinical margin of noninferiority, many of which are difficult to prove and may be based on subjective assessments. We discuss these assumptions and give examples where they are not met. Regardless of the methods that are used, the margin of noninferiority must reflect what patients and health care providers are willing to balance for the possible benefits of the new intervention for fewer adverse events or less invasiveness or cost.