Monotherapy comparative trials: equivalence and differences in clinical trials.

Investigators are familiar with the concept of clinical trial design to detect differences. Equivalence studies set out to define how similar treatments might be. They become important for two reasons: (1) similarities may be as clinically important as differences and (2) in therapeutic areas with drugs of proven efficacy already marketed, it may be ethically difficult to perform placebo-control studies. If equivalence is rigorously defined (the minimal clinically important difference), they could represent a route to licensing (cancer chemotherapy and antibiotics). Equivalence will be defined by the limits of 95% confidence intervals for a comparison being constrained within pre-defined limits. As such, studies need larger numbers of subjects rather than difference studies, and intention-to-treat analysis may no longer be the more conservative approach.