RE: change calculation of WRES?

From: Martin Bergstrand <martin.bergstrand>
Date: Tue, 25 Aug 2009 16:04:49 +0200

Dear Nele,

Individual weighted residuals (IWRES) have nothing to do with the =
parameter
estimation in NONMEM. IWRES are calculated and put in table files =
purely as
a diagnostic variable. This way they can be helpful among other things =
to
design a suitable RUV model (and that is what I really think you need to

Normally I would not want to add weighting to different parts of the =
data
based on my expectations. If I anticipated the case of lower residual
unexplained variability (RUV) with time I would include such a feature =
in my
RUV model and estimate parameters to describe it (and also evaluate =
it’s
significance). The easiest check to do is to estimate one magnitude of
residual error for early samples and one for late (see an example below =
for
a simple additive RUV) .

;------------------------------------------------------------------------=
---
---------------------------------------------

IF(TIME.LT.X) THEN ; X = Time limit dividing =
early
and late time points

W = THETA(x) ; THETA (x) = =
standard
deviation (SD) for RUV of early samples

ELSE

W = THETA(y) ; THETA (y) = SD for =
RUV of
late samples

ENDIF

Y = IPRED+W*EPS(1)

IRES = DV-IPRED

IWRES = IRES/W

\$SIGMA 1 FIX ; Fixing SIGMA to =
variance
1 allows us to estimate the scaling factor W on standard deviation scale

;------------------------------------------------------------------------=
---
---------------------------------------------

I have no experience with a continuous RUV model that describes =
decreasing
RUV with time. If the data is informative enough I sure that it is =
possible
though. An example could look something like this:

W0 = THETA(x) ; SD =
for W
at time = 0

W1HL = THETA(y) ; =
Half-life of
time dependent RUV

WL = THETA(z) ; SD =
of
non time dependent RUV

W1K = LOG(2)/W1HL =

W1 = (W0- W2) * EXP(-W1K*TIME)

W = W1 + WL

Y = IPRED+W*EPS(1)

\$SIGMA 1 FIX

;------------------------------------------------------------------------=
---
---------------------------------------------

I hope this is of some help to you.

Kind regards,

Martin Bergstrand, MSc, PhD student

-----------------------------------------------

Division of Pharmacokinetics and Drug Therapy,

Department of Pharmaceutical Biosciences, Uppsala University

-----------------------------------------------

P.O. Box 591

SE-751 24 Uppsala

Sweden

-----------------------------------------------

<mailto:martin.bergstrand
martin.bergstrand

-----------------------------------------------

Work: +46 18 471 4639

Mobile: +46 709 994 396

Fax: +46 18 471 4003

From: owner-nmusers
On
Behalf Of nele.kaessner
Sent: den 25 augusti 2009 14:21
To: nmusers
Subject: [NMusers] change calculation of WRES?

Dear nmusers,

I have a question which I hope is not too trivial for the group. I am
currently analyzing some data where I have more trust in values at late =
time
points. Therefore, I would like WRES to be a function of time, putting =
more
weight on late time points. In the help guide I found that WRES can be
influenced by SPTWO, however no real documentation exists (or I am not =
aware
of it) about how to use it. Does anybody have an example for me of how =
to
code this?
Moreover, I noticed that no matter how I describe my weighting for =
IWRES,
this does not at all seem to influence my objective function or =
parameter
values. When evaluating a model, most people consider anyway that WRES =
is
what counts, as IWRES are in most cases ok anyway. So my very simple
question is: If this does not influence any of this and I don't use =
IWRES to
decide if a model is good or bad, why bother at all to calculate them? I
noticed that the standard errors seem to change depending on which =
weighting
I use for IWRES. Can anybody explain this?

Thanks and best wishes
Nele
______________________________________________________________

Dr. Nele Käßner
Pharmacometrics -- Modeling and Simulation

Nycomed GmbH
Byk-Gulden-Str. 2
D-78467 Konstanz, Germany

Fon: (+49) 7531 / 84 - 4759
Fax: (+49) 7531 / 84 - 94759

mailto: nele.kaessner
http://www.nycomed.com

County Court: Freiburg, Commercial Register HRB 701257
Chairman Supervisory Board: Charles Depasse
Management Board: Dr. Barthold Piening, Gilbert Rademacher, Dr. Anders
Ullman

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Received on Tue Aug 25 2009 - 10:04:49 EDT

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