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

posted by Helmut Homepage – Vienna, Austria, 2019-09-10 01:27 (1661 d 19:30 ago) – Posting: # 20567
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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.

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