ANVISA: TIE, sample size [RSABE / ABEL]

posted by Helmut Homepage – Vienna, Austria, 2015-06-02 18:00 (3541 d 04:20 ago) – Posting: # 14896
Views: 9,708

Hi ElMaestro,

❝ […] But then realised that of course no agency will be enforcing such a weird and unjustified requirement.


No? IMHO, it is not more unjustified than EMA’s. The EMA had no negative results from arbitrarily widening the AR to 0.70~1.43 (pre-2006, 2×2 crossover sufficient; widening also for AUC!) or to 0.75~1.33 (2006+, replicate design, Cmax only). There are hundreds (?) of products authorized according to those requirements. This “evidence” explains EMA’s cap on the CVWR of 50%. They didn’t want to reach beyond what they have accepted before.
On the contrary FDA’s scaling came out of the blue… For CVs > ~50% the restriction on the PE of 0.80~1.25 is more important than the CI. Since in Canada (1991+) only the PE of Cmax has to lie with 0.80~1.25 there is some evidence across the pond that it “works” as well. Experience with AUC? Nada.

Reading ANVISA’s response over and over again, I gather that they mean #1 in order to be on the safe side (“EMA accepts reference-scaling for five years now. Let’s be slightly more con­ser­va­tive.”). At least some of the inflation of the Type I Error observed with EMA’s “method” vanishes (I expect still a TIE of ~0.06 at 40%). Until Detlew releases an (experimental?) update for PowerTOST’s *.scABEL functions (regulator="ANVISA") one can only assume the worst in sample size estimation, i.e., unscaled ABE, theta0=0.9, CV=0.4

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

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

Complete thread:

UA Flag
Activity
 Admin contact
23,379 posts in 4,913 threads, 1,661 registered users;
253 visitors (0 registered, 253 guests [including 23 identified bots]).
Forum time: 21:20 CET (Europe/Vienna)

Science is what you know.
Philosophy is what you don’t know.    Bertrand Russell

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