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RE: OMEGA BLOCK with mixture model?

From: Mats Karlsson <mats.karlsson>
Date: Thu, 16 Apr 2009 13:07:27 +0200

Hi Steve,

For a one-compartment model I think these are differences:

1) DIAG(3) is more restrictive than BLOCK(2) in the sense that only positive
correlation between CL/F and V/F can be estimated
2) DIAG(3) is less restrictive than BLOCK(2) in the sense that different
transformations can be used for F
3) DIAG(3) provides an EBE that can be used for diagnostic purposes (DIAG(3)
and BLOCK(2) would give the same estimates for the same model so I don't
understand your comment of var(F) being higher than cov(CL/F,V/F))
4) DIAG(3) may facilitate covariate model building (although this is minor
as you with BLOCK(2) can put the same relationship in in two places)
5) If there truly is a mixture in F1, then I think DIAG(3) has a advantages
over BLOCK(2) in number of parameters (two fewer) needed to describe the
variability model
6) If some additional assumptions can be reliably made, such as all
variability in F1 is truly in bioavailability and bioavailability is
restricted to be between 0 and 1, some additional info may be extracted from
the data for example by .

I would not rank any of these as major differences (expect possibly the
mixture aspect which I've never tried).

For two- or three-compartment models the advantages are that if indeed the
main covariance structure between CL/F, V1/F, Q/F, V2/F is a joint positive
correlation due to variability in bioavailability, fu etc, then a DIAG(5) is
more parsimonious than a BLOCK(4).

Mats

Mats Karlsson, PhD
Professor of Pharmacometrics
Dept of Pharmaceutical Biosciences
Uppsala University
Box 591
751 24 Uppsala Sweden
phone: +46 18 4714105
fax: +46 18 471 4003


-----Original Message-----
From: Stephen Duffull [mailto:stephen.duffull
Sent: Thursday, April 16, 2009 10:13 AM
To: Mats Karlsson; drmould
nmusers
Subject: RE: [NMusers] OMEGA BLOCK with mixture model?

Mats

> With oral data only I would normally model with BLOCK(2) on
> CL/F and V/F or a DIAG(3) on CL/F, V/F and relative F. The
> latter may have some advantages for diagnostics, covariate
> model building etc.

I have often seen these two options considered. I am unclear as to the
advantages of DIAG(3) over BLOCK(2)? In theory it would seem that they
should be identical. In practice it seems that DIAG(3) is more relaxed
since it is not required that the variance of relative F if reassigned to
the covariance of (CL/F, V/F) [under BLOCK(2)] yields a positive definite
matrix.

I presume an advantage wrt covariate model building would be access to the
EBEs of F_i. However, given the variance of F_i may exceed the covariance
of (CL/F, V/F) then I wonder if this is a real advantage or an artefact of
numerical procedures?

I am keen to learn more about real advantages of application of DIAG(3) as
an alternative to BLOCK(2).

Steve
--
Professor Stephen Duffull
Chair of Clinical Pharmacy
School of Pharmacy
University of Otago
PO Box 913 Dunedin
New Zealand
E: stephen.duffull
P: +64 3 479 5044
F: +64 3 479 7034

Design software: www.winpopt.com
Received on Thu Apr 16 2009 - 07:07:27 EDT

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