title: Distribution of the two-sample t-test statistic following blinded sample size re-estimation.
abstract: We consider the blinded sample size re-estimation based on the simple one-sample variance estimator at an interim analysis. We characterize the exact distribution of the standard two-sample t-test statistic at the final analysis. We describe a simulation algorithm for the evaluation of the probability of rejecting the null hypothesis at given treatment effect. We compare the blinded sample size re-estimation method with two unblinded methods with respect to the empirical type I error, the empirical power, and the empirical distribution of the standard deviation estimator and final sample size. We characterize the type I error inflation across the range of standardized non-inferiority margin for non-inferiority trials, and derive the adjusted significance level to ensure type I error control for given sample size of the internal pilot study. We show that the adjusted significance level increases as the sample size of the internal pilot study increases. Copyright © 2016 John Wiley & Sons, Ltd.
authors: Forest Laboratories, Harborside Financial Center Plaza V, Jersey City, 07311, NJ, USA.
authors: Kaifeng
authors: K
authors: Lu
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D006801:Humans; D010865:Pilot Projects; D011336:Probability; D012107:Research Design; D018401:Sample Size
keywords: adaptive design; blinding; internal pilot study; non-inferiority; type I error