Morrissey, McEntegart, and Lang (2010) showed that in multicenter studies with equal allocation to several treatment arms, the modified Zelen's approach provides excellent within-center and across-study balance in treatment assignments. In this article, hierarchical balancing procedures for equal allocation to more than two arms (with some elements different from earlier versions) and their unequal allocation expansions that incorporate modified Zelen's approach at the center level are described. The balancing properties of the described procedures for a case study of a multiregional clinical trial with 1:2 allocation where balance within regions as well as in other covariates is required are examined through simulations.
Keywords: Hierarchical dynamic allocation; Modified Zelen’s approach; Multicenter study; Multiregional study; Unequal allocation.