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RegisterAppropriate wording for a protocol [Two-Stage / GS Designs]
posted by Helmut 
– Vienna, Austria, 2019-09-09 23:27 – Posting: # 20567
Views: 446
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. 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.
» » 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. 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
![[image]](https://static.bebac.at/img/CC by.png)
The quality of responses received is directly proportional to the quality of the question asked. ☼
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Cheers,
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. ☼
Science Quotes
Complete thread:
- Appropriate wording for a protocol Elena777 2019-09-09 19:34 [Two-Stage / GS Designs]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Appropriate wording for a protocol ElMaestro 2019-09-09 21:39
- Appropriate wording for a protocol Helmut 2019-09-09 23:27
- Appropriate wording for a protocol Ohlbe 2019-09-10 10:27
- Which country? Helmut 2019-09-09 23:17
- Which country? Elena777 2019-09-11 20:24
- EEU-rules, TSD-methods (lengthy answer) Helmut 2019-09-12 01:31
- EEU-rules, TSD-methods (lengthy question) Astea 2019-09-14 14:56
- n2 based on PK metric with higher CV Helmut 2019-09-16 11:50
- EEU-rules, TSD-methods (lengthy question) Astea 2019-09-14 14:56
- EEU-rules, TSD-methods (lengthy answer) Helmut 2019-09-12 01:31
- Which country? Elena777 2019-09-11 20:24
- Appropriate wording for a protocol ElMaestro 2019-09-09 21:39
Ing. Helmut Schütz