It is the opposite way around for me [R for BE/BA]

posted by ElMaestro  – Belgium?, 2020-07-15 16:25 (106 d 23:49 ago) – Posting: # 21701
Views: 9,137

Hi again,

to me it is exactly the opposite way around:
A model with more than one variance component is a mixed model. I am of the impression that FDA and EMA have both been in a slight predicament with their guidances because they have both been "somewhat" aware of the specification/convergence issues with REML; hence both went in a direction with all effect s fixed as done explicitly by EMA and implicitly by FDA (when they use GLM for swr) in the guidance.
My contribution here is solely to open someone's eyes to the fact that we may not need to rely on a normal linear model for s2wr in a TRR/RTR/RRT design.

I would much more like to think of this thread as a contribution to regulators defining the next iteration of giudelines/guidances. Whether they will see it as an advantage to use REML to derive s2wr now it is shown to be doable (not causing convergence issues, because it is not involving the silly and unestimable s2wt component), is of course their decision solely. I have done my part.

For consideration further down the line, for those who enter discussions about estimator bias being catastrophic: Which estimator is more biased when handling RRT/RTR/TRR: the s2wr you get from the linear model or the one you get via REML? What would your answer imply for any future recommendations for guidelines/guidances?
(I am not a hardliner myself: I am usually thinking biased estimators are still useful estimators)

This thread already caught the attention of a number cruncher at an agency across the Atlantic unofficially, so I am OK with it all:-)

I could be wrong, but...

Best regards,

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

Complete thread:

 Admin contact
21,180 posts in 4,415 threads, 1,476 registered users;
online 5 (0 registered, 5 guests [including 2 identified bots]).
Forum time: Friday 15:14 CET (Europe/Vienna)

The idea is to try and give all the information to help others
to judge the value of your contribution;
not just the information that leads to judgment
in one particular direction or another.    Richard Feynman

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