http://www3.interscience.wiley.com/journal/113489609/abstract


Research Article

Adaptive design method based on sum of p-values

Mark Chang[size=-1] *

Millennium Pharmaceuticals Inc., Cambridge, MA 02139, U.S.A.

email: Mark Chang (mchang@mpi.com)

[size=-1]*Correspondence to Mark Chang, Millennium Pharmaceuticals Inc., Cambridge, MA 02139, U.S.A.
Ph.D.

Keywords

adaptive design • sample size re-estimation • flexible design • group sequential design

Abstract

Bauer and Kohne proposed an adaptive design using Fisher's combination of independent p-values based on subsamples from different stages (Biometrics 1994; 50(4):1029-1041). Their method provides great flexibility in the selection of statistical methods for hypothesis testing of subsamples. However, the choices for the stopping boundaries are not flexible enough to meet practical needs (Biometrics 2001; 57(3): 886-891). In this paper, an adaptive design method is proposed using linear combination of the independent p-values. The method provides great flexibility in the selection of stopping boundaries and no numerical integration is required for the two-stage designs. The stopping boundaries and p-values can be calculated manually. The operating characteristics of the adaptive designs are studied using computer simulations with and without sample size adjustment. Examples are presented for superiority and non-inferiority trials with different endpoints (normal, binary, and survival) under different adaptations. The statistical efficiency of the proposed method is compared with other methods based on conditional power. Copyright © 2006 John Wiley & Sons, Ltd.

Received: 30 September 2005; Accepted: 5 October 2006

Digital Object Identifier (DOI)

10.1002/sim.2755  About DOI