RE: Block versus diagonal omega
I am not sure there is one single statistical test you can use like we
do with covariate selection (forward followed by backward deletion
method).
The easiest way to deal with this problem would be first to use a stable
method like importance sampling assisted by MAP estimation (IMPMAP in
NONMEM7) and getting the full variance covariance matrix and correlation
matrix. NONMEM7 will give you also like SADAPT the standard errors
associated with each correlation coefficient. A way to categorize these
correlation coefficients would be to look at each correlation mean +- 2
standard errors and see if it crosses the zero cutoff. If so, you would
assume this correlation not to be statistically significant. Once all
the not statistically significant correlations are deleted, you have
your new blocks to be considered (I guess you have sometimes to change
the order of your parameters to define this new block in NONMEM7) and
you refit your model with this new blocks. Of course, this is an
approximation but at least it allows you ranking the most important
correlations based on both their mean but also their corresponding
standard errors.
A pure diagonal variance covariance matrix will affect the outcome of
your subsequent simulations and usually would inflate the response
variability across the population as important correlations are may be
missing.
Serge Guzy; Ph.D
President, CEO; POP_PHARM; INC;
www.poppharm.com
[email protected]
510 684 87 40
Quoted reply history
From: [email protected] [mailto:[email protected]]
On Behalf Of Berg, Alexander K., Pharm.D., Ph.D.
Sent: Wednesday, August 25, 2010 12:20 PM
To: [email protected]
Subject: [NMusers] Block versus diagonal omega
Hello -
I was curious if someone from the group could perhaps describe the basis
for deciding whether to use a block (variance and covariance) versus
diagonal (variance only) form of omega. Specifically, what tests if any
can be performed to decide between the two forms and are there certain
situations where one is preferred over the other as I often see only the
diagonal form used. Any help would be much appreciated -
Al Berg, PhD/PharmD
Clinical Pharmacology Fellow
Mayo Clinic - Rochester
[email protected]
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