Analysis of two-period crossover design in a multicenter clinical trial.

A technique is discussed for analyzing a two-period crossover design for a multicenter trial using identical study protocols. The technique is a modification of the analysis originally proposed by Grizzle (1965, Biometrics 21, 467-480; 1974, Biometrics 30, 727) for analyzing a two-period crossover design when study is not a factor. A mixed model using the first baseline as a covariate is analyzed to increase the power of the test of significance of the treatment-by-period interaction. The baseline values are also used in a preliminary test.