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Controlling type 1 error rate for sequential, bioequivalence studies with crossover designs
Author(s) -
Rasmussen Hans E.,
Ma Rick,
Wang Jessie J.
Publication year - 2018
Publication title -
pharmaceutical statistics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.421
H-Index - 38
eISSN - 1539-1612
pISSN - 1539-1604
DOI - 10.1002/pst.1911
Subject(s) - bioequivalence , estimator , type i and type ii errors , sample size determination , statistics , crossover , crossover study , inflation (cosmology) , econometrics , nominal level , mathematics , confidence interval , medicine , computer science , pharmacokinetics , artificial intelligence , physics , alternative medicine , pathology , theoretical physics , placebo
Summary Sample size reestimation in a crossover, bioequivalence study can be a useful adaptive design tool, particularly when the intrasubject variability of the drug formulation under investigation is not well understood. When sample size reestimation is done based on an interim estimate of the intrasubject variability and bioequivalence is tested using the pooled estimate of intrasubject variability, type 1 error inflation will occur. Type 1 error inflation is caused by the pooled estimate being a biased estimator of the intrasubject variability. The type 1 error inflation and bias of the pooled estimator of variability are well characterized in the setting of a two‐arm, parallel study. The purpose of this work is to extend this characterization to the setting of a crossover, bioequivalence study with sample size reestimation and to propose an estimator of the intrasubject variability that will prevent type 1 error inflation.