Sequential trial with B method of Potvin [Two-Stage / GS Designs]

posted by Helmut Homepage – Vienna, Austria, 2015-10-01 20:13 (3101 d 13:01 ago) – Posting: # 15515
Views: 10,543

Hi 2×John,

❝ In a sequential clinical trial conducted like a B method of Potvin, we have Cmax and AUC both not bioequivalent. Cmax has a power <80% (71.5%), and AUC>80% (84.6%).

❝ AUC 0-30min calculated by protocol is bioequivalent.

❝ In the protocol it was not specified how to proceed in this situation.


I assume you are talking about the interim analysis after stage 1.

❝ Can we calculate a new n and pass to the second phase? Or we must stop the trial?


That’s a stupid situation indeed. Following the scheme you could continue according to the results for Cmax, but would have to stop ’cause of AUC. Since for regulatory acceptance you have to show BE for both – and there is a chance for Cmax – well, cough, did I say before that this a stupid situation?
What you could try: Estimate the total sample size for Cmax, assume that the GMR of AUC stays the same in the pooled analysis, and calculate the CI with the higher degrees of freedom. Does the CI shrink enough? If no, think twice whether you should proceed.

Can you give us some numbers to play with? n1 (if unbalanced, nRT and nTR), GMRs, CVs.

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

UA Flag
Activity
 Admin contact
22,957 posts in 4,819 threads, 1,636 registered users;
105 visitors (0 registered, 105 guests [including 3 identified bots]).
Forum time: 08:15 CET (Europe/Vienna)

With four parameters I can fit an elephant,
and with five I can make him wiggle his trunk.    John von Neumann

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5