Special Issue Paper
Dose-finding design driven by efficacy in onco-hematology phase I/II trials
Article first published online: 11 MAR 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Statistics in Medicine
Special Issue: Sixth International French Society of Statistics meeting on statistical methods in biopharmacy: Recent advances and trends in statistics as applied to clinical trials
Volume 30, Issue 13, pages 1574–1583, 15 June 2011
How to Cite
Seegers, V., Chevret, S. and Resche-Rigon, M. (2011), Dose-finding design driven by efficacy in onco-hematology phase I/II trials. Statist. Med., 30: 1574–1583. doi: 10.1002/sim.4152
- Issue published online: 19 MAY 2011
- Article first published online: 11 MAR 2011
- Manuscript Accepted: 2 NOV 2010
- Manuscript Received: 1 FEB 2010
- phase I/II trials;
We present an adaptive model-based procedure for dose finding in phase I/II clinical trials when both efficacy and toxicity responses are available. In this setting, previous designs aimed at identifying the maximum tolerated dose as a surrogate for efficacy or the most successful dose, defined as the dose with the highest probability of efficacy without toxicity. Rather than using this definition of success, we propose considering all responses conditionally on the probability that dose-limiting toxicity is under a pre-specified threshold. The presented approach uses a joint model for the probability of an efficacy response and toxicity, and is evaluated through simulations. A retrospective application to a Phase I trial conducted in chronic lymphocytic leukemia is presented. Copyright © 2011 John Wiley & Sons, Ltd.