Is there a danger of “biocreep” with non-inferiority trials?

Background Non-inferiority (NI) trials test a hypothesis that a new treatment is inferior to standard treatment only to a negligible degree. Bio-creep basically refers to the cyclical phenomenon where a slightly inferior treatment becomes the active control for the next generation of NI trials which over time leads to degradation of the efficacy of the investigational treatment [1,2]. We studied the effect estimates from an unselected set of all the registered non-inferiority trials conducted within a seven-year period. The aim was to determine the pre and post trial distribution of the true effect in NI trials from this data using meta-analytic methods.