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How to think about the different determination methods?

From: yhb5442387
Date: Tue, 2 Mar 2010 23:15:27 +0800 (CST)

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!


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.
Colm Farrell
Senior Director, PKPDM&S
ICON Development Solutions
2 Globeside
Globeside Business Park
Bucks SL7 1TB
Phone: + 44 (0)1628 496404
Mobile: +44 (0)771 5750127
Email: Colm.Farrell

From:owner-nmusers m [mailto:owner-nmusers
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.

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Received on Tue Mar 02 2010 - 10:15:27 EST

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