From: "Eltahtawy, Ahmed" <Ahmed.Eltahtawy@pharma.com>
Subject: PRED VS WRES
Date: Fri, 27 Jul 2001 14:58:24 -0400
Dear All,
I have a question for the group about Pred vs Wres plots. I pooled data for
IV, IR, SR formulations and the IV gives me the most biased PRED VS WRES
pattern (S shape trend)!! In spite of using the flexible error model
(add+prop). Does anyone have any experience or explanation for this?.
would a separate error model for each formulation be reasonable? I tempted
even to analyze the data separately? Or just remove the IV data? As I don't
have the actual sampling times.
Thanks for your time in advance.
Regards
Ahmed
PRED VS WRES
From: Lewis B Sheiner <lewis@c255.ucsf.edu>
Subject: Re: PRED VS WRES
Date: Fri, 27 Jul 2001 12:32:43 -0700
WRES tends to be diagnostic for the within-individual (i.e PK) model.
If by "S shape trend" you mean that the residuals follow a trend to be
first >0 and then <0, then this suggests that you need to further
elaborate your PK structural model (e.g., a 2 compartment model instead
of a 1-compartment model).
And if this were so, it would make sense that it would be seen most readily with
the IV
data rather than with dosage forms exhibiting slower absorption.
A better plot, in my opinion, for diagnosing the adequacy of
the subject-specific mdoel is IPRED vs IWRES.
--
_/ _/ _/_/ _/_/_/ _/_/_/ Lewis B Sheiner, MD (lewis@c255.ucsf.edu)
_/ _/ _/ _/_ _/_/ Professor: Lab. Med., Biophmct. Sci., Med.
_/ _/ _/ _/ _/ Box 0626, UCSF, SF, CA, 94143-0626
_/_/ _/_/ _/_/_/ _/ 415-476-1965 (v), 415-476-2796 (fax)
From: "Eltahtawy, Ahmed" <Ahmed.Eltahtawy@pharma.com>
Subject: RE: PRED VS WRES
Date: Fri, 27 Jul 2001 15:57:49 -0400
Yes, The WRES tend to be first >0 and then <0. The fit to the IV data
alone is little better with the 2 comp Model. Unfortunately, this is not the
case with the IR and SR formulations. When all the data is pooled together
I opted for 1 cmp. Model. I don't think a mixture model would be of any
help. I will try the IPRED VS IWRES; but I still can't understand how an IV
gives the worst diagnostics.. Thanks
Regards
Ahmed
From: "Ferrin Harrison 301-827-3213 FAX 301-480-2825" <HARRISONF@cder.fda.gov>
Subject: Pred vs Wres
Date: Fri, 27 Jul 2001 16:23:26 -0400 (EDT)
What models for an entry compartment would conceal a downstream compartment?
In particular, could the SR rate be sufficiently slow to conceal one of the IV
compartments, rendering one compartment comparable to infinite rate of
elimination or equilibration?
By conceal I mean render difficult or impossible to estimate for the data
available. I can't conceive of an entry compartment mathematically neutralizing
a downstream compartment.
From: "Eltahtawy, Ahmed" <Ahmed.Eltahtawy@pharma.com>
Subject: RE: Pred vs Wres
Date: Fri, 27 Jul 2001 17:07:02 -0400
I have a dual absorption model to describe the complex absorption for the
SR data. One of these is really slow..
Regards
Ahmed