ABSTRACT
Wittes and Brittain (1990) and Gould and Shih (1992, 1998) discussed
methods of blinded SSR. In contrast to unblinded SSR, blinded SSR as-
sumes that the actually realized effect size estimate is not revealed through
unblinding the treatment code. In blinded sample-size reestimation, in-
terim data are used without unblinding treatment assignment to provide
an updated estimate of a nuisance parameter in order to update the sample
size for the trial based on the estimate. Nuisance parameters mentioned in
this context are usually the variance for continuous outcomes. Wittes et
al. (1999) and Zucker et al. (1999) investigated the performance of various
blinded and unblinded SSR methods by simulation. They observed some
slight type-I error violations in cases with small sample size. Kieser and
Friede (2003) and Friede and Kieser (2006) suggested a method of blinded
sample size. Blinded sample reestimation is generally well accepted by
regulators (ICH, 1999).
