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

posted by Helmut Homepage – Vienna, Austria, 2019-09-09 23:27 (609 d 09:43 ago) – Posting: # 20567
Views: 5,803

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 🖖
Helmut Schütz
[image]

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

Complete thread:

Activity
 Admin contact
21,446 posts in 4,483 threads, 1,511 registered users;
online 21 (0 registered, 21 guests [including 12 identified bots]).
Forum time: Tuesday 09:10 CEST (Europe/Vienna)

The fact that some geniuses were laughed at
does not imply that all who are laughed at are geniuses.    Carl Sagan

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