Liu J P, Weng C S
Berlex Laboratories, Inc., Wayne, NJ 07470, USA.
Stat Med. 1995 Apr 30;14(8):853-61. doi: 10.1002/sim.4780140813.
The current applications of Schuirmann's two one-sided tests procedure for the original scale ignore the variability of the least squares mean of the reference formulation when it substitutes for the unknown reference average of pharmacokinetic responses. We propose a modified two one-sided test procedure that takes into account the variability of the least squares mean of the reference formulation. The non-parametric version of the modified procedure is also available. We conducted a simulation study to examine the true level of significance and empirical power of four current parametric and non-parametric two one-sided tests procedures under a 2 x 2 crossover design with different combinations of sample size, intrasubject variability, and correlation between the two responses from a subject. Both theoretical results and empirical evidence show that the true level of significance of the current two one-sided tests procedures converges to 0.5 when the correlation of the two responses approaches 1. However, not only is the modified two one-sided tests procedure a test of size alpha, but empirical evidence indicates it is also an unbiased test. The modified non-parametric procedure also controls the size of the tests and is competitive even under normality assumption.
Schuirmann双侧检验程序在原始量表中的当前应用，在使用参考制剂的最小二乘均值替代药代动力学反应的未知参考均值时，忽略了参考制剂最小二乘均值的变异性。我们提出了一种改进的双侧检验程序，该程序考虑了参考制剂最小二乘均值的变异性。改进程序的非参数版本也可用。我们进行了一项模拟研究，以检验在2×2交叉设计下，样本量、受试者内变异性以及受试者两种反应之间的相关性的不同组合情况下，四种当前参数和非参数双侧检验程序的实际显著性水平和检验效能。理论结果和实证证据均表明，当两种反应的相关性接近1时，当前双侧检验程序的实际显著性水平收敛于0.5。然而，改进的双侧检验程序不仅是一个大小为α的检验，而且实证证据表明它也是一个无偏检验。改进的非参数程序也能控制检验的大小，并且即使在正态性假设下也具有竞争力。
