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A comparative study of restricted randomization procedures for multiarm trials with equal or unequal treatment allocation ratios
Authors:Yevgen Ryeznik  Oleksandr Sverdlov
Affiliation:1. Department of Mathematics, Uppsala University, Uppsala, Sweden;2. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden;3. Early Development Biostatistics, Novartis Institutes for Biomedical Research, East Hanover, NJ, USA
Abstract:Randomization designs for multiarm clinical trials are increasingly used in practice, especially in phase II dose‐ranging studies. Many new methods have been proposed in the literature; however, there is lack of systematic, head‐to‐head comparison of the competing designs. In this paper, we systematically investigate statistical properties of various restricted randomization procedures for multiarm trials with fixed and possibly unequal allocation ratios. The design operating characteristics include measures of allocation balance, randomness of treatment assignments, variations in the allocation ratio, and statistical characteristics such as type I error rate and power. The results from the current paper should help clinical investigators select an appropriate randomization procedure for their clinical trial. We also provide a web‐based R shiny application that can be used to reproduce all results in this paper and run simulations under additional user‐defined experimental scenarios.
Keywords:allocation ratio preserving  dose ranging  multiarm trial  randomization design  unequal allocation
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