An oncology clinical trial design with randomization adaptive to both short- and long-term responses

Abstract

In oncology clinical trials, both short-term response and long-term survival are important. We propose an urn-based adaptive randomization design to incorporate both of these two outcomes. While short-term response can update the randomization probability quickly to benefit the trial participants, long-term survival outcome can also change the randomization to favor the treatment arm with definitive therapeutic benefit. Using generalized Friedman’s urn, we derive an explicit formula for the limiting distribution of the number of subjects assigned to each arm. With prior or hypothetical knowledge on treatment effects, this formula can be used to guide the selection of parameters for the proposed design to achieve desirable patient number ratios between different treatment arms, and thus optimize the operating characteristics of the trial design. Simulation studies show that the proposed design successfully assign more patients to the treatment arms with either better short-term tumor response or long-term survival outcome or both.