Bioequivalence Design with Sampling Distribution Segments

Abstract: In bioequivalence design, power analyses dictate how much data must be collected to detect the absence of clinically important effects. Power is computed as a tail probability in the sampling distribution of the pertinent test statistics. When these test statistics cannot be constructed from pivotal quantities, their sampling distributions are approximated via repetitive, time-intensive computer simulation. We propose a novel simulation-based method to quickly approximate the power curve for many such bioequivalence tests by efficiently exploring segments (as opposed to the entirety) of the relevant sampling distributions. Despite not estimating the entire sampling distribution, this approach prompts unbiased sample size recommendations. We illustrate this method using two-group bioequivalence tests with unequal variances and overview its broader applicability in clinical design. All methods proposed in this work can be implemented using the developed dent package in R.