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http://dx.doi.org/10.29220/CSAM.2019.26.2.163

Phase II two-stage single-arm clinical trials for testing toxicity levels  

Kim, Seongho (Biostatistics Core, Karmanos Cancer Institute/Wayne State University)
Wong, Weng Kee (Department of Statistics, UCLA)
Publication Information
Communications for Statistical Applications and Methods / v.26, no.2, 2019 , pp. 163-173 More about this Journal
Abstract
Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. A concern of safety studies is 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 as well as use simulation studies to ascertain their properties. We provide a real-life application and a free R package gen2stage to facilitate direct use of two-stage designs in a safety study.
Keywords
safety; single-stage design; tolerability; toxicity; two-stage design;
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