Bioequivalence Trials with the Incomplete 3 × 3 Crossover Design

Abstract

In bioequivalence trials, one often considers two or more generic products with the original one. The 3 x 3 crossover design can be adopted to evaluate the two generic candidates with a brand name drug, rather than conducting two separate 2 x 2 crossover trials. Dropouts, however, are more likely to occur due to various administrative reasons when we consider a higher order crossover design. A modified method, which was originally given by Chow and Shao (1997), is extended to compare two generic products with a reference in the incomplete 3 x 3 crossover design. A simulation study and discussion are also presented.

Bioequivalence trial with two generic drugs in 2 × 3 crossover design with missing data

“…When determining the bioequivalence of multiple test drugs and a reference drug, performing several separate 2 × 2 crossover trials proves less efficient than performing one higher-order crossover trial (Lim et al, 2005). We proposed the statistical inference of 2 × 3 crossover design with missing data to assess the bioequivalence between two generic drugs with the reference drug.…”

“…Chow and Shao (1997) proposed a general statistical method to compare a generic drug to the reference one in a two sequence, three period crossover design with unbalanced or incomplete data. Lim et al (2005) extended their method in a 3 × 3 crossover design and this paper also modifies Lim et al's way in a 2 × 3 crossover design.…”

“…Such a deletion of a sequence would allow for a precise estimate of treatment effect while utilizing the same or less number of subjects; therefore, more ethically and economically favorable. Recently, Lim et al (2005) proposed a statistical method of assessing average bioequivalence in 3 × 3 crossover design when some data are missing. Lim's method is a modified version of Chow and Shao (1997) in 3 × 3 crossover design.…”

The analgesic effect of music on cold pressor pain responses: The influence of anxiety and attitude toward pain

“…The second issue addressed in the present study was to choose a research design suitable for comparing pain responses based on individual participant variability. Crossover designs are useful for avoiding the influence of confounding factors while enhancing efficiency, controlling for individual differences by assigning each participant to all treatment conditions [ 23 , 24 ]. A previous study by Choi et al [ 11 ] utilized a 2x2 crossover design to show that music has an analgesic effect during cataract surgery.…”