ABSTRACT
This chapter derives formulas for sample size calculation for comparing intrasubject variabilities and intrasubject CVs under both replicated crossover designs and parallel designs with replicates. It provides formulas for sample size calculation for comparing intersubject variabilities and total variabilities, respectively, under both crossover designs and parallel designs and discusses some practical issues. In practice, two methods are commonly used for comparing intrasubject CVs. One is proposed by Chow and Tse, which is referred to as conditional random effects model. The other one is suggested by Quan and Shih, which is a simple one-way random effects model. The total variability is simply the sum of the intrasubject and intersubject variabilities. In practice, it is of interest to test for equality, noninferiority/superiority, and similarity between treatments in terms of the intrasubject, intersubject, and/or total variabilities. When the variability of the test drug is much larger than that of the reference drug, safety of the test drug could be a concern.
