Wilcoxon–Mann–Whitney test for stratified samples and Efron's paradox dice

Two-treatment multi-center clinical trials are the most common type of clinical trials in practice. The aim of this paper is to discuss a curious property of certain standard nonparametric procedures used in the analysis of such clinical trials. Different analyses of a simulated data example are presented, which lead to contrasting and surprising results. The source of the potentially misleading outcome is then explored while relating the simulated data with the concept of Efron's paradox dice and the notion of nontransitivity. With the root of the problem established, an alternate nonparametric method from the literature is shown to address the problem. Finally, pointing out an interpretational concern of using the alternate procedure, a modification to this procedure is also suggested and corresponding theoretical results are presented.