A More Powerful Average Bioequivalence Analysis for the 2 × 2 Crossover

Abstract

The 2 × 2 crossover is commonly used to establish average bioequivalence of two treatments. In practice, the sample size for this design is often calculated under a supposition that the true average bioavailabilities of the two treatments are almost identical. However, the average bioequivalence analysis that is subsequently carried out does not reflect this prior belief and this leads to a loss in efficiency. We propose an alternate average bioequivalence analysis that avoids this inefficiency. The validity and substantial power advantages of our proposed method are illustrated by simulations, and two numerical examples with real data are provided.

Keywords:

• ANCOVA
• Bioequivalence
• Bootstrap
• Crossover trials

Mathematics Subject Classification:

• 62J10
• 62P10

Acknowledgments

The authors are grateful to Jim Kost and Tom Bradstreet for providing the crossover data sets used in Sec. 3, and to an anonymous referee for comments and suggestions which greatly improved the manuscript.

Notes

*Results based on 1,000 simulations, each of which used B = 5,000 bootstrapped samples.