Interaction in crossover studies: a modified analysis with more sensitivity

The crossover trial has an intuitive appeal to clinicians because each patient is used as his own control. Thus, between-subject variability of symptoms is eliminated. However, this study design suffers from the bias of treatment-by-period interaction. If, for example, the effect of the first treatment period carries on into the next one, then it influences the response to the latter period (carryover effect). A second problem is, that the standard approach (Hills-Armitage analysis) for interaction has a low sensitivity. An alternative method that looks at the performance of the separate treatment groups and not, as the standard approach, at the means of the groups is presented. This alternative approach does have more sensitivity than the standard in the common clinical situation where there is interaction in just one of the treatment groups. This study shows that this is so. However, the standard approach is more sensitive in the case of two-group interaction. One approach supplements the other.