Communications for Statistical Applications and Methods

The Korean Statistical Society (한국통계학회)
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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)
  • Received : 2018.08.21
  • Accepted : 2019.01.09
  • Published : 2019.03.31
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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.

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