Article first published online: 16 MAR 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Statistics in Medicine
Volume 31, Issue 18, pages 1944–1960, 15 August 2012
How to Cite
Lai, T. L., Lavori, P. W. and Shih, M.-C. (2012), Sequential design of phase II–III cancer trials. Statist. Med., 31: 1944–1960. doi: 10.1002/sim.5346
- Issue published online: 16 JUL 2012
- Article first published online: 16 MAR 2012
- Manuscript Accepted: 19 JAN 2012
- Manuscript Revised: 18 OCT 2011
- Manuscript Received: 24 FEB 2011
- generalized likelihood ratio statistics;
- group sequential clinical trials;
- phase II–III designs;
- survival analysis
Although traditional phase II cancer trials are usually single arm, with tumor response as endpoint, and phase III trials are randomized and incorporate interim analyses with progression-free survival or other failure time as endpoint, this paper proposes a new approach that seamlessly expands a randomized phase II study of response rate into a randomized phase III study of time to failure. This approach is based on advances in group sequential designs and joint modeling of the response rate and time to event. The joint modeling is reflected in the primary and secondary objectives of the trial, and the sequential design allows the trial to adapt to increase in information on response and survival patterns during the course of the trial and to stop early either for conclusive evidence on efficacy of the experimental treatment or for the futility in continuing the trial to demonstrate it, on the basis of the data collected so far. Copyright © 2012 John Wiley & Sons, Ltd.