USE OF THE REPEATED CROSS-OVER DESIGN IN ASSESSING BIOEQUIVALENCE - (WITHIN AND BETWEEN SUBJECTS VARIABILITY - SCHUIRMANN CONFIDENCE-INTERVALS ESTIMATION)

In 1992, the Division of Bioequivalence in the Office of Generic Drugs published a guide to Statistical procedures for bioequivalence studie s using a standard two-treatments cross-over design (1). This paper de scribes the application of the guidelines to a practical protocol and the recent Proc MIXED (SAS(R)) will be shown to be much more convenien t than the traditional Proc GLM for theoretical and practical reasons (correct estimation of residuals, analysis of the within-subjects vari ation, direct calculation of the Schuirmann 90% Confidence Intervals). This new procedure was applied to a study protocol on riluzole (Rilut ek(R)) including a replicate design with the within-subject and betwee n-subject variances being estimated on Cmax and AUC biopharmaceutic pa rameters.