Maximum type I error rate inflation from sample size reassessment when investigators are blind to treatment labels.

ABSTRACT: Consider a parallel group trial for the comparison of an experimental treatment to a control, where the second-stage sample size may depend on the blinded primary endpoint data as well as on additional blinded data from a secondary endpoint. For the setting of normally distributed endpoints, we demonstrate that this may lead to an inflation of the type I error rate if the null hypothesis holds for the primary but not the secondary endpoint. We derive upper bounds for the inflation of the type I error rate, both for trials that employ random allocation and for those that use block randomization. We illustrate the worst-case sample size reassessment rule in a case study. For both randomization strategies, the maximum type I error rate increases with the effect size in the secondary endpoint

SUBMITTER: Zebrowska M 

PROVIDER: S-EPMC4851240 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature