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Re: FO vs FOCE, sequential vs simultaneous

From: Leonid Gibiansky <LGibiansky>
Date: Tue, 09 Dec 2008 12:33:25 -0500

Hi Alan,


I used all datasets that I had, and I was not able to find any problem
where FO was superior to FOCE.

Not-converged FOCE is better, in my opinion, than converged FO (although
you can always check using diagnostic plots).

If you cannot use FOCE due to time restrictions, it is better to use FO
than just abandon modeling. Still, I would try to run the final model
with FOCEI.

Concerning sequential vs simultaneous: there are several points to
consider, and this is usually relates to the PK-PD case. For PK-PD, the
main question is the comparison of PK and PD variabilities. Usually, PK
variability is smaller, and PK data are more reliable. Then, sequential
modeling can be more warranted. If PK and PD variabilities are similar
(both residual and inter-subject) you can use joint fit. I usually do PK
first, then PK-PD, and then try to fit combined model at the very last

For parent-metabolite case, both sets of data are equally reliable (or
not reliable), and variability is usually similar. Then the question
boils down to time and convenience. Again, I usually do parent fist,
then fix parameters and do metabolite, and then, if possible, do
simultaneous fit. This often saves time: parent model is more simple, it
can be done in standard ANDANs for 1-2 compartment models that are much
quicker. You can experiment freely with random effect, covariates,
residual error, etc. Joint model often needs to be solved using ADVAN5,
7 or even $DES which are more CPU-consuming. You want to do minimum
number of runs here. Thus, you want to start with good parent model, and
study metabolite part only. The final joint run fits all parts together.


Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
e-mail: LGibiansky at
tel: (301) 767 5566

Xiao, Alan wrote:
> Dear All,
> I know this is an old topic, too, but would like to see the statistics.
> When you have a dataset with about 10% of dense Phase II data (predose, 2, 4, 8, and 12 hrs post dose on day 1 and at steady state, twice-daily dose regimen) and about 90% of very sparse Phase III data (1-2 samples/patient), which method do you prefer: FO or FOCE? or FO for model development but FOCE for model refinement/finalization? If FOCE is not practical because of long run-time or numerical difficulties in converge, do you stop here or would you use FO?
> Thanks,
> Alan
Received on Tue Dec 09 2008 - 12:33:25 EST

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