Equivalence trials: methodologic analysis.

Abstract

Therapeutic clinical research is based on randomized controlled trials (RCTs) that compare a new drug with a placebo or--less frequently--with an active substance (a drug with proven efficacy for that disease), trying to determine whether one is better than the other, or both are the same. These trials are called "superiority trials", because the aim is to prove that the new drug is more efficacious than the classic one (or the placebo). Besides superiority trials between two drugs, or a drug and a placebo, there are trials called "equivalence trials", in which two drugs (or the same drug with two galenic formulations) are compared in order to prove their pharmacologic and clinical equivalence. Because it is impossible to prove that two (or more) interventions are exactly equivalent, these trials have to be designed in such a way as to show that the two treatments do not differ by more than a certain pre-defined "equivalence margin". This type of trial is especially useful when the classic treatment has proven efficacy, but the new one is safer, easier to use or cheaper, for example. In this article we present the guidelines which all equivalence trials should follow to be considered valid. These methodological rules certify as to the equivalence between drugs, eliminating errors and biases that are commonly found in the literature.