All,
I feel the need to clarify my response as well. I agree that the
systematic/mechanistic effects of pregnancy term on the PK should definitely
be explored first (get the fixed effects right before postulating additional
IOV random effects) and I leave that to the subject-matter experts. My
r
All,
It feels like there might be some clarification in order. What I was
suggesting in the below was a plot of the individual random effect values
vs. pregnancy term, in order to explore possible (non-random) covariate
effects of pregnancy stage. I think this is consistent with what Nick,
Stephen
Paul
As another "rule" protein binding decreases throughout pregnancy to a low at
term due to dilution. This with a purported increase in CL makes for
interesting modelling.
I think as an initial approach a biologically plausible model is better than
moving down the various variance routes.
Paul
Another suggestion
As a general rule, drug clearance increases during pregnancy due to increased
blood perfusion, especially during the last trimesters. You might also consider
a time covariate effect over your clearance rather than on etas, with fewer
parameters.
Best wishes,
Armel
Armel
Hi,
Within subject variability has two parts -- a random component that is
you have tried to describe using between occasion variability (AKA IOV)
-- and a fixed (or predictable) component that in your case is
associated with each stage of pregnancy.
Your code only has the random component f
Paul,
You might try plotting your etas 6-9 vs. trimester (coded at four levels) to
ensure that the IOV is truly random by occasion, as your model assumes.
Obviously, it is not unheard of that the IOV should be much larger than IIV,
but I wouldn't start with that assumption. Usually there is at leas
Hi Paul,
When you treat each occasion as a different patient you get
subject-by-occasion specific predictions of all the parameters in your model
(or at least for those parameters in which you include an IIV eta)...not
just clearance. Thus, it is not surprising that you might get a better fit
by
Original Message
Subject: occasions during pregnancy
From:yu...@pitt.edu
Date:Tue, March 1, 2011 10:49 am
To: "nm nm"
--
Hi all nmusers,
I thank all who
Pharsight is please to offer a two day, hands-on workshop which will give
participants an opportunity to become familiar with Phoenix NLME and Connect, a
next generation nonlinear mixed effects modelling platform. Instruction will be
given on basic data management and exploratory graphical and t
