Adaptive two-stage designs for single-arm phase IIA cancer clinical trials

Biometrics. 2004 Jun;60(2):482-90. doi: 10.1111/j.0006-341X.2004.00193.x.


The main purpose of a phase IIA trial of a new anticancer therapy is to determine whether the therapy has sufficient promise against a specific type of tumor to warrant its further development. The therapy will be rejected for further investigation if the true response rate is less than some uninteresting level and the test of hypothesis is powered at a specific target response rate. Two-stage designs are commonly used for this situation. However, in many situations investigators often express concern about uncertainty in targeting the alternative hypothesis to study power at the planning stage. In this article, motivated by a real example, we propose a strategy for adaptive two-stage designs that will use the information at the first stage of the study to either reject the therapy or continue testing with either an optimistic or a skeptic target response rate, while the type I error rate is controlled. We also introduce new optimal criteria to reduce the expected total sample size.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biometry*
  • Clinical Protocols
  • Clinical Trials, Phase II as Topic / methods*
  • Clinical Trials, Phase II as Topic / statistics & numerical data
  • Hodgkin Disease / drug therapy
  • Humans
  • Models, Statistical
  • Neoplasms / therapy*