title: The questionable use of unequal allocation in confirmatory trials.
abstract: Randomization is the standard means for addressing known and unknown confounders within the patient population in clinical trials. Although random assignment to treatment arms on a 1:1 basis has long been the norm, many 2-armed confirmatory trials now use unequal allocation schemes where the number of patients receiving investigational interventions exceeds those in the comparator arm. In what follows, we offer 3 arguments for why investigators, institutional review boards, and data and safety monitoring boards should exercise caution when planning or reviewing 2-armed confirmatory trials involving unequal allocation ratios. We close by laying out some of the conditions where uneven allocation can be justified ethically.
authors.affiliation: From the Studies for Translation, Ethics, and Medicine Group (STREAM), Biomedical Ethics Unit, McGill University, Montreal, Canada.
authors.forename: Spencer Phillips
authors.initials: SP
authors.lastname: Hey
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kimmelman
mesh_terms: D000818:Animals; D002985:Clinical Protocols / Q000592:standards*; D006801:Humans; D011897:Random Allocation; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards*; D012107:Research Design / Q000592:standards