Name: Chen

Firstname: Gang

Title: Statistician

Institution: CDER?FDA

Street: 5600 Fishers Ln

City: Rockville

Zip-Code: 20857

Country: USA

Phone: 3015945774

Fax: 3018274590

Email: chenga@cder.fda.gov

Authors: Gang Chen, Yong-Cheng Wang, and George Chi

Title: Multiplicity Issues in Sample Size Re-estimation for Active Control Non-inferiority Trials

Abstract: The sample size required for testing non-inferiority hypotheses depends on an appropriate assessment of the control effect and the assumption of the new treatment effect relative to the control. Test of the null hypothesis with a fraction retention of the control effect is conditionally equivalent to an asymmetric two confidence interval testing procedure, where the control effect is estimated by the lower limit of a 100(1-?n?)%, 0 < ƒƒnƒƒnƒƒzƒnconfidence interval [1]. The value of this ƒƒnis not known ahead of time for most clinical benefit endpoints and the sample size of the study cannot be reasonably estimated at the study design stage. In this presentation, a randomized 2-stage design is proposed for active control non-inferiority studies. The ƒƒncan be evaluated at the end of first stage of the study so that the sample size can be re-estimated. A simulation has been done to exam the potential for the type 1 error inflation due to the interim sample! size adjustment and an analysis method for controlling the type I error inflation has been proposed. An example based on an approved NDA data is given.

References: [1]. Rothmann, M, Li, N, Chen, G, Chi, G, and Tsou, HH. Non-inferiority methods for mortality trials. ASA Proceedings of the Biopharmaceutical Section 2001.