Randomization and allocation procedures for master protocol trials of single-arm studies

In this paper we propose and examine randomization and allocation procedures in master protocol trials where each subtrial is performed as a single-arm study, which is motivated mainly by rare diseases. The subtrial analysis is done by comparing the single-arm observations data to historical data or expert judgment and following prespecified decision rules, without using data from any other study in the master protocol trial. The objective of this paper is to examine relevant options for participant allocation procedures in a variety of patterns in which the subtrials enter the master protocol trial, such as umbrella, platform and perpetual patterns. Our simulation study shows that our proposed allocation procedures using the predictive probability of current study success may bring substantial efficiency gains in the master protocol trial, making a clever allocation of the in-trial participants to achieve study success declarations sooner, benefiting the out-of-trial population.