An efficient analysis of covariance model for crossover thorough QT studies with period-specific baseline days

2013 ◽  
Vol 12 (4) ◽  
pp. 192-200 ◽  
Author(s):  
Kaifeng Lu
2003 ◽  
Vol 28 (1) ◽  
pp. 45-70 ◽  
Author(s):  
Michael Harwell

Results from exact statistical theory and Monte Carlo studies have provided evidence that the test size and power of the F test in analysis of covariance are sensitive to violations of certain assumptions. However, a comprehensive summary of the effect of assumption violations has not been available. In this article, meta-analytic methods are used to summarize the results of Monte Carlo studies of the test size and power of the F test in the single-factor, fixed-effects analysis of covariance model, updating and extending narrative reviews of this literature. Monte Carlo results for the nonparametric rank-transform test in the analysis of covariance model are also analyzed. Guidelines for using these tests when assumptions are violated are presented to promote more judicious use of these procedures.


2019 ◽  
Vol 28 (12) ◽  
pp. 3808-3821 ◽  
Author(s):  
Georg Zimmermann ◽  
Markus Pauly ◽  
Arne C Bathke

It is well known that the standard F test is severely affected by heteroskedasticity in unbalanced analysis of covariance models. Currently available potential remedies for such a scenario are based on heteroskedasticity-consistent covariance matrix estimation (HCCME). However, the HCCME approach tends to be liberal in small samples. Therefore, in the present paper, we propose a combination of HCCME and a wild bootstrap technique, with the aim of improving the small-sample performance. We precisely state a set of assumptions for the general analysis of covariance model and discuss their practical interpretation in detail, since this issue may have been somewhat neglected in applied research so far. We prove that these assumptions are sufficient to ensure the asymptotic validity of the combined HCCME-wild bootstrap analysis of covariance. The results of our simulation study indicate that our proposed test remedies the problems of the analysis of covariance F test and its heteroskedasticity-consistent alternatives in small to moderate sample size scenarios. Our test only requires very mild conditions, thus being applicable in a broad range of real-life settings, as illustrated by the detailed discussion of a dataset from preclinical research on spinal cord injury. Our proposed method is ready-to-use and allows for valid hypothesis testing in frequently encountered settings (e.g., comparing group means while adjusting for baseline measurements in a randomized controlled clinical trial).


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