The effect of sample size re-estimation on type I error rates when comparing two binomial proportions

Abstract

Estimation of sample size is an important and critical procedure in the design of clinical trials. A trial with inadequate sample size may not produce a statistically significant result. On the other hand, having an unnecessarily large sample size will definitely increase the expenditure of resources and may cause a potential ethical problem due to the exposure of unnecessary number of human subjects to an inferior treatment. A poor estimate of the necessary sample size is often due to the limited information at the planning stage. Hence, the adjustment of the sample size mid-trial has become a popular strategy recently. In this work, we introduce two methods for sample size re-estimation for trials with a binary endpoint utilizing the interim information collected from the trial: a blinded method and a partially unblinded method. The blinded method recalculates the sample size based on the first stage’s overall event proportion, while the partially unblinded method performs the calculation based only on the control event proportion from the first stage. We performed simulation studies with different combinations of expected proportions based on fixed ratios of response rates. In this study, equal sample size per group was considered. The study shows that for both methods, the type I error rates were preserved satisfactorily.