Re: [NMusers] Two compartment model with fixed omega parameters

From: Waroonrat Sukarnjanaset <waroonrat_at_hotmail.com>
Date: Wed, 28 Jun 2017 09:48:45 +0000

Dear Martin and Rik,


Thank you so much for your helpful suggestions, I really appreciate it.


Could you please recommend me which estimation methods would be the possibl=
e methods to estimate IIV for V2 and Q?


Sincerely,


Waroonrat

________________________________
From: Rik Schoemaker <rik.schoemaker_at_occams.com>
Sent: Tuesday, June 27, 2017 11:29 AM
To: Waroonrat Sukarnjanaset
Cc: nmusers_at_globomaxnm.com
Subject: RE: [NMusers] Two compartment model with fixed omega parameters


Dear Waroonrat,



I fully support Martin’s suggestions below, but to come back to your orig=
inal question: the fact that IIVs are set to zero for V2 and Q does not mea=
n the second compartment is ‘gone’. If you would examine your model pre=
dictions, inclusion of the second compartment -even without IIV- would resu=
lt in the characteristic bend in the elimination phase of your compound whe=
n viewed on the log-scale. It is quite often that NONMEM FOCE-I cannot esti=
mate IIV for V2 and Q and fixing them to zero can result in perfect predict=
ions of your observed concentration profiles including the two-compartment =
behaviour. No-one would claim that these parameters are in fact the same fo=
r every single subject, just that the data cannot support making them diffe=
rent for your subjects in this case.



Kind regards,



Rik Schoemaker, PhD

Occams Coöperatie U.A.
Malandolaan 10
1187 HE Amstelveen
The Netherlands

www.occams.com<http://www.occams.com>

[http://www.occams.com/assets/images/PAGE-1.jpg]<http://www.occams.com/>

Occams<http://www.occams.com/>
www.occams.com
Occams: a high-quality strategic services provider to clients in the pharma=
ceutical industry



+31 20 441 6410
rik.schoemaker_at_occams.com<mailto:rik.schoemaker_at_occams.com>



[cid:image003.png_at_01D2EF49.733D6460]







From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] On=
 Behalf Of Martin Bergstrand
Sent: 27 June 2017 11:30
To: Waroonrat Sukarnjanaset <waroonrat_at_hotmail.com>
Cc: nmusers_at_globomaxnm.com
Subject: RE: [NMusers] Two compartment model with fixed omega parameters



Dear Waroonrat,



To know if a model “adequately describe the data” you need to study mod=
el diagnostics. Read more for example here: http://onlinelibrary.wiley.com/=
doi/10.1002/psp4.12161/full



The AIC numbers in your case indicate that the two compartment model is a m=
uch better description of your data than the one compartment model (read on=
 AIC here: https://en.wikipedia.org/wiki/Akaike_information_criterion). How=
ever, this is only a relative comparison and as pointed out before does not=
 say anything about whether any of the models “adequately describe the da=
ta”.



All the best,



Martin Bergstrand, Ph.D.

Senior Consultant

Pharmetheus AB



From: owner-nmusers_at_globomaxnm.com<mailto:owner-nmusers_at_globomaxnm.com> [ma=
ilto:owner-nmusers_at_globomaxnm.com<mailto:owner-nmusers_at_globomaxnm.com>] On =
Behalf Of Waroonrat Sukarnjanaset
Sent: Tuesday, June 27, 2017 10:52 AM
To: nmusers_at_globomaxnm.com<mailto:nmusers_at_globomaxnm.com>
Subject: [NMusers] Two compartment model with fixed omega parameters



Dear NMusers,



I have tried to find an appropriate base model.


I found that two compartment model with fixed Omega of V2 and Omega of Q =
= 0 (AIC 1860.17) provided smaller AIC than one compartment model (AIC 19=
21.83) did.



From these findings (no variability on V2 and Q), is it suggesting that one=
 cpt model could adequately describe the data?



I would truly appreciate it if you could give me some suggestions.



Kind regards,



Waroonrat




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Received on Wed Jun 28 2017 - 05:48:45 EDT

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