Phase II Two-Stage Single-Arm Clinical Trials for Testing Toxicity Levels

Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. In safety studies, a main concern is that there may be too many patients who experience an adverse event. We show that Simon's two-stage designs for efficacy studies can be similarly used to design a two-stage safety study by modifying some of the design parameters. Given the type I and II error rates and the proportion of adverse events experienced in the first stage cohort, we prescribe a procedure whether to terminate the trial or proceed with a stage 2 trial by recruiting additional patients. We study the relationship between a two-stage design with a safety endpoint and an efficacy endpoint and use simulation studies to ascertain their properties. We provide a real-life application and a free R package gen2stage to facilitate direct use of such two-stage designs in a safety study.