Two-stage clinical trial stopping rules.

Two-stage stopping rules for clinical trials are considered. The nominal significance level needed for the second-stage test, for any choice of first-stage significance level, is derived for rules with overall significance levels of .01 and .05 and for studies with either half or two-thirds of the patients analyzed in the first stage. A graphical demonstration is given of the inherent tradeoff between power and expected sample size (or probability of early termination). A specific rule, intermediate to those advocated by Pocock (1977, Biometrika 64, 191-199) and O'Brien and Fleming (1979, Biometrics 5, 549-556), is recommended.