Appropriate wording for a protocol [Two-Stage / GS Designs]

posted by Helmut Homepage – Vienna, Austria, 2019-09-10 01:27 (2130 d 01:12 ago) – Posting: # 20567
Views: 14,295

Hi ElMaestro,

❝ ❝ 1. Should we include the information that evaluation after stage 1 completion should be performed assuming GMR=0.95?


❝ I would do so.


So would I.

❝ ❝ 2. Should we describe the maximum number of subjects who can be included in whole or in stage 2?


❝ I would only put a cap on it if you can refer to simulations having done exactly so (having done so in exactly your way of capping).


From a regulatory perspective this is not necessary. Any futility rule (like max. n2) decreases the chance to show BE if compared to a published method without one. Hence, if the type I error was controlled in a method without a futility rule, the TIE will always be lower with a futility rule. However, if a futility rule is too strict, you may shoot yourself in the foot since power might be compromised. To check that, sim’s are a good idea indeed.

❝ ❝ 3. Any other information that should be clearly stated in order to be accurate and to satisfy regulatory authorities?


❝ Exact decision tree, and exact values for alphas, desired power level, and power being calculated using GMR=0.95.


Yep.

❝ ❝ 4. What if BE criteria are met after stage 1, but estimated power is too low (e.g. 30%)?


❝ It is not a crime to be lucky.


Absolutely. As one of the grumpy old men: Forget power, doesn’t matter.

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
23,428 posts in 4,929 threads, 1,691 registered users;
32 visitors (0 registered, 32 guests [including 14 identified bots]).
Forum time: 02:40 CEST (Europe/Vienna)

To know that we know what we know,
and to know that we do not know what we do not know,
that is true knowledge.    Nicolaus Copernicus

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