ABEL vs. ABE [Power / Sample Size]

posted by BEQool  – 2024-02-04 20:24 (20 d 20:12 ago) – Posting: # 23853
Views: 397

Sorry for my late response.

❝ Oh dear! EMA region, really‽ Outright bizarre.

No no, EMA has not asked this question (yet :-D). I just wanted to make a hypothetical example and mentioned EMA in order to use ABEL and not RSABE (it is probably not even relevant but anyway).

❝ BTW, why do you want to use a partial replicate design and not one of the 2-sequence 3-period full replicate designs (TRT|RTR or TRR|RTT)? Acceptable for the EMA (see the Q&A document and this post for examples). Same degrees of freedom and similar sample sizes. More informative because you can also estimate CVwT, which is useful in designing other studies (quite often CVwT < CVwR and you need a smaller sample size). In the partial replicate you have to assume CVwT = CVwR, which is often wrong.

Yes it could also be any replicate design (2-sequence 3-period full replicate design or 2-sequence 4-period full replicate designs), 3-sequence 3-period partial replicate design here was just an example.
Nevertheless, a deficiency letter regarding 2-sequence 3-period full replicate design from an European agency was already received (it was answered successfully) so 3-sequence 3-period partial replicate design is now used sometimes instead.

❝ By ‘regular study’ are you meaning a simple crossover? Even if you observed CVw ≥30% I would be cautious. That’s only a hint of a highly variable reference. See this article for details.

My bad, I meant a pivotal study. I wanted to ask if agencies can ask you to justify using any replicate design when the drug's CVw in the study is for example around 20% - but you already answered that below.

❝ There is nothing to justify. Any study in a replicate design can also be assessed for ABE. My – former – best enemy once said »From a purely statistical perspective, all studies should be performed in a replicate design.« One of the rare occasions I agree with him.

Thank you for the answers, everything is clear now.


Complete thread:

UA Flag
 Admin contact
22,911 posts in 4,806 threads, 1,635 registered users;
33 visitors (1 registered, 32 guests [including 6 identified bots]).
Forum time: 16:36 CET (Europe/Vienna)

The history of statistics is like a telephone directory:
the plot is boring, full of numbers and the cast is endless.    Stephen Senn

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