The limitations of equivalence and non-inferiority trials

Equivalence and non-inferiority trials are becoming more and more popular. Typically, they compare the effects of a treatment of interest with the current gold-standard treatment as the comparator. However, for this approach, the definition of equivalence or non-inferiority margins (NIM) is crucial, and no clear rules for their definition exist. We criticized the practice of these trials of being over-inflationary in favor of (erroneous) equivalence, and we outlined our critique with some study examples comparing psychodynamic treatments with current first-line treatments for mental disorders. Here we answer to a commentary of Leichsenring et al. to our paper. Although focusing on our commentary, these authors are less arguing against our conclusions, but they address issues of study conduct, and lack of appreciation of our examples. However, the crucial question is: What is the risk of erroneous equivalence conclusions that we want to accept as responsible clinicians and scientists? We conclude that the scientific community has to define better and clearer criteria for NIMs. We do not believe that it is ethically justifiable to recommend a treatment that is 10 or 20% less effective than the current gold standard interventions.