@article { WOS:000320005100011,
	title = {An Insight into the Properties of a Two-Stage Design in Bioequivalence Studies},
	journal = {PHARMACEUTICAL RESEARCH},
	volume = {30},
	number = {7},
	year = {2013},
	month = {JUL},
	pages = {1824-1835},
	publisher = {SPRINGER/PLENUM PUBLISHERS},
	type = {Article},
	address = {233 SPRING ST, NEW YORK, NY 10013 USA},
	abstract = {Unveil the properties of a two-stage design (TSD) for bioequivalence (BE) studies. A TSD with an upper sample size limit (UL) is described and analyzed under different conditions using Monte Carlo simulations. TSD was split into three branches: A, B1, and B2. The first stage included branches A and B1, while stage two referred to branch B2. Sample size re-estimation at B2 relies on the observed GMR and variability of stage 1. The properties studied were \% BE acceptance, \% uses and \% efficiency of each branch, as well as the reason of BE failure. No inflation of type I error was observed. Each TSD branch exhibits different performance. Stage two exhibits the greatest \% BE acceptances when highly variable drugs are assessed with a low starting number of subjects (N-1) or when formulations differ significantly. Branch A is more frequently used when variability is low, drug products are similar, and a large N-1 is included. BE assessment at branch A is very efficient. The overall acceptance profile of TSD resembles the typical pattern observed in single-stage studies, but it is actually different. Inclusion of a UL is necessary to avoid inflation of type I error.},
	keywords = {adaptive design, bioequivalence, Monte Carlo simulations, Sample Size, two-stage design},
	issn = {0724-8741},
	doi = {10.1007/s11095-013-1026-3},
	author = {Karalis, Vangelis and Macheras, Panos}
}
