Optimal, minimax and admissible two-stage design for phase II oncology clinical trials

BMC Med Res Methodol. 2020 May 20;20(1):126. doi: 10.1186/s12874-020-01017-8.

Abstract

Background: The article aims to compare the efficiency of minimax, optimal and admissible criteria in Simon's and Fleming's two-stage design.

Methods: Three parameter settings (p1-p0 = 0.25-0.05, 0.30-0.10, 0.50-0.30) are designed to compare the maximum sample size, the critical values and the expected sample size for minimax, optimal and admissible designs. Type I & II error constraints (α, β) vary across (0.10, 0.10), (0.05, 0.20) and (0.05, 0.10), respectively.

Results: In both Simon's and Fleming's two-stage designs, the maximum sample size of admissible design is smaller than optimal design but larger than minimax design. Meanwhile, the expected samples size of admissible design is smaller than minimax design but larger than optimal design. Mostly, the maximum sample size and expected sample size in Fleming's designs are considerably smaller than that of Simon's designs.

Conclusions: Whenever (p0, p1) is pre-specified, it is better to explore in the range of probability q, based on relative importance between maximum sample size and expected sample size, and determine which design to choose. When q is unknown, optimal design may be more favorable for drugs with limited efficacy. Contrarily, minimax design is recommended if treatment demonstrates impressive efficacy.

Keywords: Admissible design; Minimax design; Optimal design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clinical Trials, Phase II as Topic
  • Humans
  • Medical Oncology
  • Neoplasms* / drug therapy
  • Probability
  • Research Design*
  • Sample Size