†Supporting information may be found in the online version of this article.
An adaptive seamless phase II/III design for oncology trials with subpopulation selection using correlated survival endpoints†
Version of Record online: 8 DEC 2010
Copyright © 2010 John Wiley & Sons, Ltd.
Volume 10, Issue 4, pages 347–356, July/August 2011
How to Cite
Jenkins, M., Stone, A. and Jennison, C. (2011), An adaptive seamless phase II/III design for oncology trials with subpopulation selection using correlated survival endpoints. Pharmaceut. Statist., 10: 347–356. doi: 10.1002/pst.472
- Issue online: 25 JUL 2011
- Version of Record online: 8 DEC 2010
- seamless design;
- subpopulation selection;
- phase II/III;
- targeted therapy;
- time-to-event endpoints
Although the statistical methods enabling efficient adaptive seamless designs are increasingly well established, it is important to continue to use the endpoints and specifications that best suit the therapy area and stage of development concerned when conducting such a trial. Approaches exist that allow adaptive designs to continue seamlessly either in a subpopulation of patients or in the whole population on the basis of data obtained from the first stage of a phase II/III design: our proposed design adds extra flexibility by also allowing the trial to continue in all patients but with both the subgroup and the full population as co-primary populations. Further, methodology is presented which controls the Type-I error rate at less than 2.5% when the phase II and III endpoints are different but correlated time-to-event endpoints. The operating characteristics of the design are described along with a discussion of the practical aspects in an oncology setting. Copyright © 2010 John Wiley & Sons, Ltd.