long half-life and large variability [Regulatives / Guidelines]

posted by ElMaestro  – Denmark, 2020-07-29 21:24 (261 d 09:55 ago) – Posting: # 21800
Views: 1,548

Hi martin,

» My interpretation of regulatoy guidelines: adding additional fixed effect factors to the factors mentioned in the guidelines is typically considered as not acceptable by regulators.

There was not a lot of concrete info in your post, but in my humble experience you are totally right where ordinary BA/BE is concerned: regulators rarely allow deviations in pivotal trials.

However, milder winds are blowing when we talk BE for biologics in EU. Here covariates found their way into the melée because many companies suggested it (and they did so because FDA wanted covariates).

I don't from the top of my head remember a case where an applicant wanted a "less obvious" fixed effect in the proposed model and was outright successful.
The new/creative/funky/funny fixed factors I have come across recently were in crossovers where we always have subjects fit as fixed. In such cases, when the proposed new fixed factors are subject-specific they don't really do anything in terms of the residual or its df's. For example, if we specify CYP phenotype as fixed factor, columns for phenotype in the model matrix would add up exactly to an intercept, so we wouldn't be going anywhere.

Pass or fail!
ElMaestro

Complete thread:

Activity
 Admin contact
21,419 posts in 4,475 threads, 1,508 registered users;
online 15 (0 registered, 15 guests [including 4 identified bots]).
Forum time: Saturday 07:19 CEST (Europe/Vienna)

I never did anything worth doing by accident,
nor did any of my inventions come by accident;
they came by work.    Thomas Alva Edison

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