UCLA

Simon’s two-stage designs are frequently used in phase II single-arm trials for efficacy studies. A concern ofsafety studies is too many patients who experience an adverse event. We show that Simon’s two-stage designsfor efficacy studies can be similarly used to design a two-stage safety study by modifying some of the designparameters. Given the type I and II error rates and the proportion of adverse events experienced in the firststage cohort, we prescribe a procedure whether to terminate the trial or proceed with a stage 2 trial by recruitingadditional patients. We study the relationship between a two-stage design with a safety endpoint and an efficacyendpoint as well as use simulation studies to ascertain their properties. We provide a real-life application and afree R package gen2stage to facilitate direct use of two-stage designs in a safety study.