Which GMR to plug in [Two-Stage / GS Designs]

posted by ElMaestro  – Belgium?, 2017-02-20 11:46 (1343 d 08:12 ago) – Posting: # 17089
Views: 10,862

Hi Yura,

there are not that many people working with these designs. But those who do have all tried to plug in the observed GMR from stage 1 for sample size calculation, rather than 0.95 as in Potvin B & C.

The result is strikingly bad news: The chance that you have a greater departure from 0.95 goes up as sample size in stage 1 goes down, so you easily end up in scenarios where you need 800 subjkects in stage 2 if you apply the observed GMR, and this may happen even if the true GMR is 0.95 or better. Of course you can put a cap on max sample size, but you are punished on power.

Heartbreaking, really!!:crying:


As stated before: At a time when you do not know the true GMR very well (such as after the first stage) it is not a particularly good idea to base decisions on it (such as final sample size).

That is why Potvin's method are great for formulations with known and controlled GMR, but not great for new formulations where you don 't know how they match. Two-stage designs are useful for unknown CV's and not much else, at least in the presrnt form.

Pilot trials suffer the exxact same issue. "They are better than nothing" is a sentence I have heard a few times, but it is often not the case. Depending on how you use the info available the info you may well decide wrongly and be punished.

I could be wrong, but...

Best regards,
ElMaestro

No, of course you do not need to audit your CRO if it was inspected in 1968 by the agency of Crabongostan.

Complete thread:

Activity
 Admin contact
21,179 posts in 4,414 threads, 1,474 registered users;
online 2 (0 registered, 2 guests [including 2 identified bots]).
Forum time: Sunday 19:59 CET (Europe/Vienna)

Mediocrity knows nothing higher than itself,
but talent instantly recognizes genius.    Arthur Conan Doyle

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5