RE: Model building
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
Quoted reply history
From: owner-nmusers
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
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Indranil Bhattacharya