Approaches to handling data when a phase II trial deviates from the pre-specified Simon's two-stage design

Stat Med. 2008 Dec 20;27(29):6190-208. doi: 10.1002/sim.3426.

Abstract

Simon's 'optimal' and 'minimax' two-stage designs are common methods for conducting phase IIA studies investigating new cancer therapies. However, these designs are rather rigid in their settings because of the pre-specified rejection rules and fixed sample sizes at each stage. In practice, we often encounter the problem that a study is unable to adhere to the event number and sample sizes of the original two-stage design. In this paper, we consider some approaches in handling situations where deviations or interruptions from the original Simon's two-stage design occur because recruitment of patients is slower than expected. We consider four scenarios and use conditional probabilities to address the issues commonly inquired by the scientific review board. We also discuss how to report p-values in these situations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Biometry / methods*
  • Clinical Trials, Phase II as Topic / statistics & numerical data*
  • Data Interpretation, Statistical
  • Female
  • Humans
  • Models, Statistical
  • Probability
  • Stochastic Processes
  • Uterine Cervical Neoplasms / drug therapy