Testing strategy in phase 3 trials with multiple doses.

In this paper, we consider multiplicity testing approaches mainly for phase 3 trials with two doses. We review a few available approaches and propose some new ones. The doses selected for phase 3 usually have the same or a similar efficacy profile, so they have some degree of consistency in efficacy. We review the Hochberg procedure, the Bonferroni procedure, and a few consistency-adjusted procedures, and suggest new ones by applying the available procedures to the pooled dose and the high dose, the dose that is thought to be more efficacious between two doses. The reason behind the idea is that the pooled dose and the high dose are more consistent than the original two doses if the high dose is more efficacious than the low dose. We compare all approaches via simulations and recommend using a procedure combining 4A and the pooling approach. We also discuss briefly the testing strategy for trials with more than two doses.