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

posted by Helmut Homepage – Vienna, Austria, 2019-09-09 23:27  – Posting: # 20567
Views: 2,165

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.

Cheers,
Helmut Schütz
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