Interval estimation of binomial proportion in clinical trials with a two-stage design
Article first published online: 13 JUN 2007
Copyright © 2007 John Wiley & Sons, Ltd.
Statistics in Medicine
Volume 27, Issue 1, pages 15–35, 15 January 2008
How to Cite
Tsai, W.-Y., Chi, Y. and Chen, C.-M. (2008), Interval estimation of binomial proportion in clinical trials with a two-stage design. Statist. Med., 27: 15–35. doi: 10.1002/sim.2930
- Issue published online: 13 DEC 2007
- Article first published online: 13 JUN 2007
- Manuscript Accepted: 16 APR 2007
- Manuscript Received: 31 MAY 2006
- coverage probability;
- Simon's design;
- truncated binomial distribution;
- two-stage design
Generally, a two-stage design is employed in Phase II clinical trials to avoid giving patients an ineffective drug. If the number of patients with significant improvement, which is a binomial response, is greater than a pre-specified value at the first stage, then another binomial response at the second stage is also observed. This paper considers interval estimation of the response probability when the second stage is allowed to continue. Two asymptotic interval estimators, Wald and score, as well as two exact interval estimators, Clopper–Pearson and Sterne, are constructed according to the two binomial responses from this two-stage design, where the binomial response at the first stage follows a truncated binomial distribution. The mean actual coverage probability and expected interval width are employed to evaluate the performance of these interval estimators. According to the comparison results, the score interval is recommended for both Simon's optimal and minimax designs. Copyright © 2007 John Wiley & Sons, Ltd.