Still SF [Two-Stage / GS Designs]
Hi Dan,
Yes.
Though I’m deeply involved in this kind of stuff I even don’t know anybody working on it.
If we take the GL literally
It’s even worse than a year ago. Do you remember this post? Since many decisions have to be taken into account in the EMA’s ABEL (CVwR >30%? CVwR >50%? GMR within 80.00–125.00?) this method itself may lead to an inflation of the type I error. The latest release of
If (‼) you succeed in convincing regulators that a pre-specified α is not necessary (te-hee) but can be estimated based on stage 1 data, it should be doable (runtime a couple of minutes at the most). Given the EMA’s skepticism concerning TSDs in general (see this post) IMHO, chances are close to nil.
❝ My question for today: is this still the case/state of science that you can not combine 2-stage and replicate designs?
Yes.
❝ A short update would be very much apreciated. In case that there is new literature available I would love if you could give references.
Though I’m deeply involved in this kind of stuff I even don’t know anybody working on it.
If we take the GL literally
“The plan to use a two-stage approach must be pre-specified in the protocol along with the adjusted significance levels to be used for each of the analyses.”
the blue part is the show-stopper.It’s even worse than a year ago. Do you remember this post? Since many decisions have to be taken into account in the EMA’s ABEL (CVwR >30%? CVwR >50%? GMR within 80.00–125.00?) this method itself may lead to an inflation of the type I error. The latest release of
PowerTOST
contains two functions which iteratively adjust α in such a way that the TIE is preserved: scABEL.ad()
for the adjustment and sampleN.scABEL.ad()
for the sample size. With this algo on the average you need four iterations to get the adjusted α. Hence, multiply the runtimes given at the end of this post by four…If (‼) you succeed in convincing regulators that a pre-specified α is not necessary (te-hee) but can be estimated based on stage 1 data, it should be doable (runtime a couple of minutes at the most). Given the EMA’s skepticism concerning TSDs in general (see this post) IMHO, chances are close to nil.
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Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- Replicated 4×2 and two-stage-design, in the same protocol Mauricio Sampaio 2015-04-06 08:37
- Replicated 4×2 and two-stage-design, in the same protocol ElMaestro 2015-04-06 08:53
- Science fiction Helmut 2015-04-06 14:20
- Science fiction Dr_Dan 2016-03-04 10:33
- mindblowing ElMaestro 2016-10-11 07:44
- Natural constant as usual; not for reference-scaling Helmut 2016-10-11 09:50
- Consistency DavidManteigas 2016-10-11 11:25
- Natural constant as usual; not for reference-scaling Helmut 2016-10-11 09:50