An adjusted two one-sided t-test for the assessment of bioequivalence with multiple doses.

In medical practice, it has been realized that noncompliance may have an impact on the therapeutic effect of a drug therapy, regardless of race, gender, and education of patients. Therefore, it is of interest to study the impact of noncompliance on drug absorption through in vivo testing. Efron and Feldman examined dose-response relationship when noncompliance is an issue. In this paper, we study bias and variation induced by noncompliance for pharmacokinetic parameters such as the area under the curve (AUC). We use bioequivalence testing as an example to demonstrate that a false conclusion could be drawn if one ignores the effect of noncompliance. We propose a new test for the assessment of bioequivalence in multiple doses. The proposed test appears to have a substantial improvement over the usual two one-sided tests based on a simulation study.

Duke Scholars

Author Shein-Chung Chow Biostatistics & Bioinformatics, Division of Biostatistics