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OJVRTM

Online Journal of Veterinary Research ©

Volume 25 (1) : 28-34, 2021.


Schuirmann’s two 1-sided and nonparametric tests for non-normal pharmacokinetic drug interactions

 

Jihao Zhou, PhD, Yulei He, MS 2, Ying Yuan, MA, MS1

 

1Department of Clinical Biostatistics, Pfizer Global Research and Development, La Jolla Laboratories, 11085 Torreyana Road, San Diego, California, 92121, USA. 2Department of Biostatistics, The University of Michigan, Ann Arbor, Michigan, 48109 USA.

 

Abstract

 

Zhou J, He Y,  Yuan Y., Schuirmann’s two 1-sided and nonparametric tests for non-normal pharmacokinetic drug interactions, Onl J Vet Res., 25(1): 28-34, 2021. Schuirmann’s two one-sided tests (TOST) approach is widely used in clinical drug-drug interaction studies. However, it requires normality assumption, which may not hold in practice. We report statistical performance of Schuirmann’s TOST procedure for non-normal data compared with nonparametric TOSTs. Monte Carlo simulations were used to generate non-normal data with different skewness and kurtosis. The statistical performances of Schuirmann’s TOST and nonparametric method-based TOSTs were compared in terms of empirical power, size and coverage probability. The nonparametric TOST approaches were based on Wilcoxon signed-rank test, Jackknife and Bootstrap methods. Our simulations show that Schuirmann’s TOST is fairly robust to slightly skewed data, but may have poor performance when data are heavily skewed. In contrast, Bootstrap-T approach consistently yields the best coverage probabilities and reasonable empirical sizes.

 

KEY WORDS drug-drug interaction, two-one sided tests, nonparametric, clinical trial.


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