Modified Zelen's Approach Randomization in Studies with Unequal Allocation

• Activity Number: 178
• Type: Contributed
• Date/Time: Monday, August 1, 2011 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Olga M. Kuznetsova*+ and Yevgen Tymofyeyev
• Companies: Merck Sharp and Dohme Corp. and Merck Sharp and Dohme Corp.
• Keywords: Randomization ; modified Zelen's approach ; unequal allocation ; multi-center study ; dynamic allocation ; partial block supplies

Abstract

Modified Zelen's approach [Zelen 1974; McEntegart 2008] is a randomization technique useful in multi-center trials where balance in treatment assignments within a center is desired. It has great balancing properties in a study with equal allocation to several treatment arms [Morrissey et al., 2010]. This technique can also be used in a study with unequal allocation, where it would provide an allocation ratio close to the targeted one within centers as well as across centers - or across strata, if the allocation is stratified by factors other than center. However, the implementation of the modified Zelen's approach for unequal allocation involves more than just imposing a constraint on within-center imbalance in treatment assignments, as is the case with equal allocation. The presentation will explain why, and offer an easy way to expand the modified Zelen's approach to unequal allocation. The expansion to unequal allocation of related allocation procedures, including dynamic allocation with partial block supplies sent to the centers, covariate-adaptive and hierarchical dynamic allocation schemes that include modified Zelen's approach at the center level, will be discussed.