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411 – Regulatory Challenges in Nonclinical Biostatistics
Expanding Brick Tunnel Randomization to Allow for Larger Imbalance in Treatment Totals in Studies with Unequal Allocation
Olga Kuznetsova
Merck & Co., Inc.
Yevgen Tymofyeyev
Janssen
In open-label studies, partial predictability of permuted block randomization provides potential for selection bias. To lessen the selection bias in two-arm studies with equal allocation, a number of allocation procedures that limit the imbalance in treatment totals at a pre-specified level, but do not require the exact balance at the ends of the blocks were developed. In studies with unequal allocation, however, the task of designing a randomization procedure that sets a pre-specified limit on imbalance in group totals has not been completely resolved. Existing allocation procedures either do not preserve the allocation ratio at every allocation or do not include all allocation sequences that comply with the pre-specified imbalance threshold. Kuznetsova and Tymofyeyev described the Brick Tunnel (BT) randomization for studies with unequal allocation that preserves the allocation ratio at every allocation and, in the two-arm case, includes all sequences that satisfy the smallest possible imbalance threshold. In this work, we expand two-arm BT randomization to allow for larger imbalance in treatment totals - which lowers selection bias in open-label studies with unequal allocation.