Carryover and the two-period crossover clinical trial.

The use of the two-period crossover trial for comparing two noncurative treatments in patients with a chronic disease is appealing since it eliminates the between-subject variability. However, the possibility of the existence of carryover effect leads many authors to advise that a parallel design be used whenever carryover is suspected. We examine this advice and quantify the degree of carryover required to make the parallel design preferable in terms of the power of the test of treatment effect and precision of the estimate of treatment difference. We conclude that in many situations this amount of carryover is substantial and unlikely to exist.