Mass weighted urn design--A new randomization algorithm for unequal allocations

Abstract

Unequal allocations have been used in clinical trials motivated by ethical, efficiency, or feasibility concerns. Commonly used permuted block randomization faces a tradeoff between effective imbalance control with a small block size and accurate allocation target with a large block size. Few other unequal allocation randomization designs have been proposed in literature with applications in real trials hardly ever been reported, partly due to their complexity in implementation compared to the permuted block randomization. Proposed in this paper is the mass weighted urn design, in which the number of balls in the urn equals to the number of treatments, and remains unchanged during the study. The chance a ball being randomly selected is proportional to the mass of the ball. After each treatment assignment, a part of the mass of the selected ball is re-distributed to all balls based on the target allocation ratio. This design allows any desired optimal unequal allocations be accurately targeted without approximation, and provides a consistent imbalance control throughout the allocation sequence. The statistical properties of this new design is evaluated with the Euclidean distance between the observed treatment distribution and the desired treatment distribution as the treatment imbalance measure; and the Euclidean distance between the conditional allocation probability and the target allocation probability as the allocation predictability measure. Computer simulation results are presented comparing the mass weighted urn design with other randomization designs currently available for unequal allocations.

Keywords: Allocation predictability; Mass weighted urn design; Treatment imbalance; Unequal allocation.