Challenges in designing comparative-effectiveness trials for antidepressants

Comparative-effectiveness antidepressant trials offer promise to provide empirical evidence for clinicians choosing among interventions. Whether such trials posit superiority or noninferiority (NI) hypotheses, they pose formidable challenges. For instance, if meaningful antidepressant differences are seen in comparative-superiority trials, they will be small. NI hypothesis testing, on the other hand, requires an a priori NI margin and evidence of trial assay sensitivity. Either design demands unusually large samples, which could render such trials infeasible.