In clinical studies, multiple comparisons of several treatments to a control with ordered categorical responses are often encountered. A popular statistical approach to analyzing the data is to use the logistic regression model with the proportional odds assumption. As discussed in several recent research papers, if the proportional odds assumption fails to hold, the undesirable consequence of an inflated familywise type I error rate may affect the validity of the clinical findings. To remedy the problem, a more flexible approach that uses the latent normal model with single-step and stepwise testing procedures has been recently proposed. In this paper, we introduce a step-up procedure that uses the correlation structure of test statistics under the latent normal model. A simulation study demonstrates the superiority of the proposed procedure to all existing testing procedures. Based on the proposed step-up procedure, we derive an algorithm that enables the determination of the total sample size and the sample size allocation scheme with a pre-determined level of test power before the onset of a clinical trial. A clinical example is presented to illustrate our proposed method.
Keywords: familywise error rate; latent normal variable model; ordered categorical response; sample size determination.
Copyright © 2014 John Wiley & Sons, Ltd.