Dear Colm
Thank you for your generous advice.
Do you mean that in the situation of 2 or 3 compartments, there is no need to
include BSV into all the pharmacokineitc parameter? As you have suggested that
we could start with eta on the parameter in the centra compartment, are there
some literatures or papers published in SCI? I have got few learning about your
suggested method.
If that step was done,the next step you advised is to check whether I could get
support additional eta terms.Do you mean the significant drop in the OFV,such
as 3.84,e.g.?
Thanks again!
Regards!
Dear Ye,
Without knowing how well sampled the data are, I would suggest starting with
fewer eta terms (start with eta on CL and V1, for example) and then see if you
can support additional eta terms.
As for the different assays, you might want to start with a single residual
variability term and then once you have got a handle on the number of etas that
you can include, go back and see if you need to partition out the residual
variability by assay.
I wouldn't consider assay as a traditional covariate.
Regards,
Colm
Colm Farrell
Senior Director, PKPDM&S
ICON Development Solutions
2 Globeside
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Email: [email protected]
From:[email protected] [mailto:[email protected]] On
Behalf Of yhb5442387
Sent: 09 February 2010 14:03
To: nmusers
Subject: [NMusers] How to think about the different determination methods?
Dear NMusers:
I am dealing with the ppf(Propofol) data collected from 3 different
centers,in which the drug concentrations ananlysis happens to be 3 different
assays.Those are GC,Hplc-UV,HPlc-fluorescence,separaterly.As a item,the assay
way is included,labeled as 1,2,3,in order.
And as an introduction from the Mannual, the assay way is arranged as the
intraindividual variability .The syntax is as follows:
IF (ASSY.EQ.1) Y=F*(1+EPS(1))
IF (ASSY.EQ.2) Y=F*(1+EPS(2))
IF (ASSY.EQ.3) Y=F*(1+EPS(3))
And by the way,the pharmacokinetics of ppf were described by a
three-compartment model.So the subroutine of advan 11,trans 4 was applied.
Of course,the combined Additive and CCV error model were considered at the
beginning,but it seems to me that the additive error was so little (0.00001)
that even could be ignored.So the CCV model was applied finally,as mentioned
above.
So there are 6 thetas(Cl,V1,Q2,V2,Q3,V3),6 etas (exp ISV model) and 3 eps in
the base model.Then the problem happened.
No matter what intial estimates I tried,the results of $EST and $COV steps
allways indicate that the model was overparactermized.
The hint of R Matrix is either singular or NON-positive semidefinite appeared
in the output files.And from the PDx-plotter,the plot of objective function Vs
iteration was fairly flat.So I am confirmed that the model was
overparactermized.In addtition,I have checked the R matrix in which some values
in the line of SG22,SG33,are 0.
Here are my questions:
Should I take the assay error as an intraindividual variability?
How about If I take it as a covariate which would have an influence on any
parameter of CL,V,and such and so on?
If there is only one eps in the intraindividual model, without the
consideration of asssy error.Does it sounds reasonable?
Thank you for any comments:
This is my last email at this year.Because next several days are the Chines
traditional Spring Festival.And I will be far away from the
laboratory and stay with my families for celebration.So,taking such a special
opportunity,I would say thanks to whom help me before ,now
and soon.
Also, BEST WISHES TOO ALL THE NMusers.Happy Spring Festival!!!
Yours sincerely,Ye hong bo.
--
工作和生活,都要开心的过.
你好,叶红波在此送上真挚的祝福.祝你开心,
叶红波
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