NONMEM Users Network Archive

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Re: Model building

From: Indranil Bhattacharya <ibhattacharya>
Date: Fri, 4 Dec 2009 12:11:18 -0500

Jurgen, thanks for your suggestions.
the thetas change according to the model I am trying to fit the data. I
always try to keep the omega to a minimum and on parameters which make more
sense from the viewpoint of population modeling.

The cell kill rate would be say around 2 logs per day.

I am just measuring total cell concentration.

Thanks

Neil

On Thu, Dec 3, 2009 at 9:38 PM, Jurgen Bulitta
<jbulitta

> Dear Neil,
>
>
>
> Two questions:
>
> 1) Could you please give us some information on the number of thetas and
> omegas,
>
> number of cellular sub-populations with different drug susceptibility, and
> typical
>
> rates of growth and killing (e.g. n Log10 killing per hour or day) in your
> model?
>
>
>
> 2) Could you please let us know what your observed variables are? (i.e. are
> you just
>
> measuring total cell concentration or are you specifically measuring
> resistant cells)
>
>
>
> Especially for the FOCE method, too many omegas on initial conditions of
> resistant
>
> subpopulation(s) that only show up later after the susceptible cells have
> been killed
>
> may cause the FOCE method to not finish successfully. I am not overly
> worried about
>
> this and tend to go for the better curve fits. Two solutions would be to
>
> 1) use MC-PEM instead of FOCE or 2) to reduce the number of OMEGAs.
>
> At least for in vitro studies, the run to run variability may be small.
>
>
>
> Best wishes
>
> Juergen
>
>
>
>
>
>
>
>
>
> *From:* owner-nmusers
> *On Behalf Of *Indranil Bhattacharya
> *Sent:* Thursday, December 03, 2009 10:41 AM
> *To:* nmusers
> *Subject:* [NMusers] Model building
>
>
>
> Hi, I am in the process of developing a PK/PD model and have a naive
> question regarding model building.
>
> I currently do not have all the PD data and more data would be available in
> the future. For the current data set, I have tried models say A to D.
>
> Now model A (cell kill) and B (cell kill +transduction) converges using
> FOCE (no CV% but I am willing to live with that) but from the RES and WRES
> plots we can clearly see that there is some bias. The fit is OK but not
> great. The ofv values are around 400.
>
> Now models B (cell cycle specific kill), C (cell + precursor cell kill
> +transduction) and D (cell cycle specific + indirect response model) do not
> converge using FO or FOCE methods but when I look at the fits from the
> terminated runs, the fits are much better than those obtained with Model A,
> and there seems very little bias. Also the ofv values are between 160-250.
>
>
>
> So my question is whether the fits, RES, WRES plots and the ofv values have
> meaning even when the minimization terminates.
>
>
>
> Regards
>
>
>
> Neil
>
> --
> Indranil Bhattacharya
>



--
Indranil Bhattacharya

Received on Fri Dec 04 2009 - 12:11:18 EST

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