The two-period crossover design with baseline measurements

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Abstract
We consider a two-period crossover study in which each patients measured on the response variable at the start as well as at the end of both periods. We examine models in which the carryover effect at the start of the second period may be different from the carryover effect at the end, and in which the correlations between observations decrease as a function of the time between them. In trials with a relatively short washout period, we recommend that the second baseline measurement not be incorporated into the analysis and that the data be evaluated by analysis of covariance, with the difference between the post-treatment values as the response variable and the first period's baseline value as the covariate. The absence of carryover effects must be assumed. When the washout period is moderately long (comparable in length to either treatment period), the preferred analysis for a difference between direct treatment effects will again generally be based on the differences between post-treatment values. An analysis based on changes from baseline would, under certain assumptions about the form of the variance-covariance matrix, be preferred only for quite long washout periods and large correlations between observations. Even then, the efficiency of the test for equality of direct effects is improved if the difference between the baseline values is used as the covariate.

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