Bioequivalence and Bioavailability Forum • AUC passes with 0.05 and Cmax with 0.0294

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

posted by Elena777 – Belarus, 2019-09-19 10:34 (2475 d 03:28 ago) – Posting: # 20615
Views: 18,678

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:

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).
❝
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 C_max 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?

Complete thread:

Appropriate wording for a protocol Elena777 2019-09-09 19:34 [Two-Stage / GS Designs]
- Appropriate wording for a protocol ElMaestro 2019-09-09 21:39
  - Appropriate wording for a protocol Helmut 2019-09-09 23:27
  - Appropriate wording for a protocol Ohlbe 2019-09-10 10:27
- Which country? Helmut 2019-09-09 23:17
  - Which country? Elena777 2019-09-11 20:24
    - EEU-rules, TSD-methods (lengthy answer) Helmut 2019-09-12 01:31
      - EEU-rules, TSD-methods (lengthy question) Astea 2019-09-14 14:56
        
        n2 based on PK metric with higher CV Helmut 2019-09-16 11:50
        
        Q&A ref Astea 2019-09-16 18:28
        
        The omniscient oracle has spoken Helmut 2019-09-17 12:27
        
        The omniscient oracle has spoken Astea 2019-09-17 20:34
        
        OT: Булга́ков Helmut 2019-09-18 12:12
        
        n2 based on PK metric with higher CV Elena777 2019-09-16 19:48
        
        AUC passes with 0.05 and Cmax with 0.0294 Helmut 2019-09-16 23:30
        
        AUC passes with 0.05 and Cmax with 0.0294 Mikalai 2019-09-18 16:56
        
        Hybrid B/C Helmut 2019-09-18 17:09
        
        AUC passes with 0.05 and Cmax with 0.0294Elena777 2019-09-19 08:34
        
        Use data of all dosed subjects Helmut 2019-09-19 15:16
        
        Use data of all dosed subjects Elena777 2019-09-19 15:27
        
        ‘Method C’ ⇒ risky Helmut 2019-09-19 16:15
        
        EEU-rules, TSD-methods (lengthy question) Elena777 2019-09-16 19:35
        
        apple tree for two-stage Astea 2019-09-16 20:39
        
        overripe apples Helmut 2019-09-16 23:37
        
        override apples Astea 2019-09-17 06:14