Randomized Phase II clinical trials

Sin Ho Jung, Daniel J. Sargent

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Traditionally, Phase II trials have been conducted as single-arm trials to compare the response probabilities between an experimental therapy and a historical control. Historical control data, however, often have a small sample size, are collected from a different patient population, or use a different response assessment method, so that a direct comparison between a historical control and an experimental therapy may be severely biased. Randomized Phase II trials entering patients prospectively to both experimental and control arms have been proposed to avoid any bias in such cases. The small sample sizes for typical Phase II clinical trials imply that the use of exact statistical methods for their design and analysis is appropriate. In this article, we propose two-stage randomized Phase II trials based on Fishers exact test, which does not require specification of the response probability of the control arm for testing. Through numerical studies, we observe that the proposed method controls the type I error accurately and maintains a high power. If we specify the response probabilities of the two arms under the alternative hypothesis, we can identify good randomized Phase II trial designs by adopting the Simons minimax and optimal design concepts that were developed for single-arm Phase II trials.

Original languageEnglish (US)
Pages (from-to)802-816
Number of pages15
JournalJournal of Biopharmaceutical Statistics
Issue number4
StatePublished - Jul 4 2014


  • Fisher's exact test
  • Minimax design
  • Optimal design
  • Two-stage design
  • Unbalanced allocation

ASJC Scopus subject areas

  • Statistics and Probability
  • Pharmacology
  • Pharmacology (medical)


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