Cross-over trials in drug development: Theory and practice

It is maintained that much research into the design and analysis of cross-over trials has been of little practical relevance to drug development. The point is illustrated using three topics: the AB/BA design, bioequivalence and multi-period designs in two treatments. It is suggested that statisticians should pay more attention to the work of fellow scientists, in particular, in the field of pharmacokinetics, and also that the philosophical-inferential base employed in examining cross-over trials has often been too narrow.