Assessment of Unequal Randomization in Clinical Trial Design

Music City Center 

Equal randomization ratio (1:1) is the most common ratio used in confirmatory clinical trials. There have been discussions on unequal randomization that it could be favored over equal randomization for many reasons including encouraging trial recruitment, reducing costs, and estimates in the treatment arm being more robust. However, unequal randomization is still rarely applied in trial design despite the benefits, as the challenge remains that there is no method to determine the optimal randomization ratio to achieve the best outcomes that balance many considerations of a trial. To address this issue, we developed a optimization framework that determines the optimal randomization ratio which maximizes a trial's probability of success and expected net value of a trial, two major concerns while designing a trial, based on trial parameters such as prior knowledge of efficacy, sample size, budget and cost. The proposed method is evaluated with simulations and a hypothetical trial. The simulation results show that how optimal randomization ratio changes with different input of trial parameters, and it can successfully reduce the cost while maintaining a high probability of success.

Randomization

Probability of success

Optimization

Trial Design

Oncology

Survival Analysis 

Biopharmaceutical Section