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: [email protected] [mailto:[email protected]] On
Behalf Of Indranil Bhattacharya
Sent: Thursday, December 03, 2009 10:41 AM
To: [email protected]
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