These two authors contributed equally to this work.
An alternative phase II/III design for continuous endpoints
Article first published online: 22 FEB 2010
Copyright © 2010 John Wiley & Sons, Ltd.
Volume 10, Issue 2, pages 105–114, March/April 2011
How to Cite
Huang, W.-S., Liu, J.-p. and Hsiao, C.-F. (2011), An alternative phase II/III design for continuous endpoints. Pharmaceut. Statist., 10: 105–114. doi: 10.1002/pst.418
- Issue published online: 22 FEB 2010
- Article first published online: 22 FEB 2010
- Manuscript Accepted: 11 JAN 2010
- Manuscript Revised: 22 DEC 2009
- Manuscript Received: 7 FEB 2009
- type I error rate;
- sample size
The success rate of drug development has been declined dramatically in recent years and the current paradigm of drug development is no longer functioning. It requires a major undertaking on breakthrough strategies and methodology for designs to minimize sample sizes and to shorten duration of the development. We propose an alternative phase II/III design based on continuous efficacy endpoints, which consists of two stages: a selection stage and a confirmation stage. For the selection stage, a randomized parallel design with several doses with a placebo group is employed for selection of doses. After the best dose is chosen, the patients of the selected dose group and placebo group continue to enter the confirmation stage. New patients will also be recruited and randomized to receive the selected dose or placebo group. The final analysis is performed with the cumulative data of patients from both stages. With the pre-specified probabilities of rejecting the drug at each stage, sample sizes and critical values for both stages can be determined. As it is a single trial with controlling overall type I and II error rates, the proposed phase II/III adaptive design may not only reduce the sample size but also improve the success rate. An example illustrates the applications of the proposed phase II/III adaptive design. Copyright © 2010 John Wiley & Sons, Ltd.