Still SF [Two-Stage / GS Designs]

posted by Helmut Homepage – Vienna, Austria, 2016-03-04 13:41  – Posting: # 16050
Views: 12,265

Hi Dan,

» My question for today: is this still the case/state of science that you can not combine 2-stage and replicate designs?


» 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: for the adjustment and 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.

Dif-tor heh smusma 🖖
Helmut Schütz

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

Complete thread:

 Admin contact
20,815 posts in 4,356 threads, 1,447 registered users;
online 17 (0 registered, 17 guests [including 11 identified bots]).
Forum time: 12:15 CEST (Europe/Vienna)

Repetition does not transform a lie into a truth.    Franklin D. Roosevelt

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