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Re: change calculation of WRES?

From: Emmanuel Chigutsa <Emmanuel.Chigutsa>
Date: Tue, 25 Aug 2009 16:21:10 +0200

Dear Nele
 
I would normally be guided by the iWRES plots against individual
predictions to determine if there is a time dependent trend that needs
to be addressed in the error model (since the drug plasma concentrations
vary with time). If so, you can use the following code in your error
model:
IF (TIME .LE. xxx) THEN
   W=yyy
   ELSE
   W=zzz
   ENDIF
 
You can estimate the time i.e. put a THETA or put a fixed value
yourself. The difference in the two values of W will tell you whether
it is necessary to have a time varying error model.
 
Further reading is available : Karlsson, Beal, Sheiner. 1995 "Three new
residual error models for population PK/PD analyses" Journal of
pharmacokinetics and biopharmaceutics, vol 23, no.6.
 
Emmanuel
 
 
Emmanuel Chigutsa (BPharm. Hons)
Research Fellow, Pharmacometrics Group
Division of Clinical Pharmacology, University of Cape Town
K-45 Old Main Building, Groote Schuur Hospital
Anzio Road, Observatory, 7925
Cape Town, South Africa
Telephone: +27 214066758
Fax: +27 214066759
Mobile: +27 782826538
Email: emmanuel.chigutsa


>>> <nele.kaessner

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 - 10:21:10 EDT

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