## AUC passes with 0.05 and Cmax with 0.0294 [Two-Stage / GS Designs]

Dear Helmut,

I`m sorry for being persistent on the topic.

❝ »First step - estimated power is less than target (80%) for Cmax and more than target for AUC, 90%CI for AUC is OK. To be in compliance with method C of Potvin, we re-calculate CI for Cmax with α=0,0294. And BE criterion for Cmax is met after this step. Finally we will have the following in a CSR: BE criterion was met for AUC using α=0,05 (90%CI) and BE criterion was met for Cmax using α=0,0294 (94,12% CI). Does it look OK?

Absolutely. The ideas behind the different alphas in Potvin C are:

1. If interim power is ≥80%, essentially your assumptions about the CV were correct. Assess the study like a fixed sample design with α 0.05. You stop anyway (pass/fail).

2. If interim power is <80%, your assumptions about the CV were not correct. Assess the study with the adjusted α 0.0294.
1. If you pass, stop.

2. If you fail, initiate the second stage.
Hence, in your example you are for Cmax in the branch 2.a. and for AUC in branch 1. All is good.

To be completely sure that I understood you in a proper way, the final question is:

First step - estimated power is less than target (80%) for Cmax and more than target for AUCt. 90%CI for AUCt is OK. As per method C of Potvin, we re-calculate CI for Cmax with α=0,0294. And BE criterion for Cmax is NOT met after this step. Then we calculate CVintra for Cmax and proceed with the second stage. What combined data should be evaluated after stage 2 completion: ONLY for Cmax or for Cmax and AUCt?