Group sequential design for comparative diagnostic accuracy studies.

Abstract

In the field of diagnostic medicine, comparative clinical trials are necessary for assessing the utility of one diagnostic test over another. The area under the receiver operating characteristic (ROC) curve, commonly referred to as AUC, is a general measure of a test's inherent ability to distinguish between patients with and without a condition. Standardized AUC difference is the most frequently used statistic for comparing two diagnostic tests. In therapeutic comparative clinical trials with sequential patient entry, fixed sample design (FSD) is unjustified on ethical and economical grounds and group sequential design (GSD) is frequently used. In this paper, we argue that the same reasoning exists for the comparative clinical trials in diagnostic medicine and hence GSD should be utilized in this field for designing trials. Since computation of the stopping boundaries of GSD and data analysis after a group sequential test rely heavily on Brownian motion approximation, we derive the asymptotic distribution of the standardized AUC difference statistic and point out its resemblance to the Brownian motion. Boundary determination and sample size calculation are then illustrated through an example from a cancer clinical trial.