| Abstract: | The two-period crossover trial is considered the most powerful means of determining the efficacy of new drugs. However, this study design is frequently invalidated by 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 bias has a low statistical sensitivity. The author recently described an alternative method entitled the clinical approach because it looks at the clinical performance of the separate treatment groups and not, as the standard approach, at the means of the groups. It may be hypothesized that this alternative approach is statistically more sensitive than the standard in situations where there is interaction in just one of the treatment groups. The present study uses two examples and a mathematical model. It shows that in case of single-group interaction the clinical approach can, indeed, detect carryover effect at a 30% lower level than the standard. On the other hand, however, the standard approach does so even at a 40% lower level than the clinical in case of two-group interaction. I conclude that one approach supplements the other and that they be used in future studies simultaneously. |
