Hello NONMEM Users,
When clearance changes over time, the classic analytical solution for the 2-compartment linear model is not correct. Nevertheless, if the change is only ~30%, one can say it is still acceptable. Time required to run an analytical and numerical models is drastically different, which can be important for decision making. Did someone had an experience submitting using analytical solution when clearance changes over time to an agency or a journal? Can it be acceptable?
Thanks,
Paul
Numerical integreaion and change in clearance over time
One option is to run all analyses in analytical ADVANs and then re-run the final model in differential equations. If the results are close, it could be used as a justification of the final model. If not, differential equations solution should be preferred, I guess. In our experience, analytical solution is usually pretty close to the differential equations but this may depend on the data (time step of records). One option to increase precision is to place extra EVID=2 records, so that the time step is smaller. Another option is to use MTIME for that, similar to:
https://www.page-meeting.org/default.asp?abstract=1361
Leonid
Quoted reply history
On 12/19/2017 6:15 PM, Pavel Belo wrote:
> Hello NONMEM Users,
>
> When clearance changes over time, the classic analytical solution for the 2-compartment linear model is not correct. Nevertheless, if the change is only ~30%, one can say it is still acceptable. Time required to run an analytical and numerical models is drastically different, which can be important for decision making. Did someone had an experience submitting using analytical solution when clearance changes over time to an agency or a journal? Can it be acceptable?
>
> Thanks,
>
> Paul
Hi Paul,
Leonid has suggested some good methods for initial exploration of the data so if you want to do a good job you can understand the magnitude of the error using a short cut.
The real problem here seems to be poor time management planning. Data does not arrive suddenly out of the blue without any warning with decisions having to be made the next day.
Nick
Quoted reply history
On 20-Dec-17 14:52, Leonid Gibiansky wrote:
> One option is to run all analyses in analytical ADVANs and then re-run the final model in differential equations. If the results are close, it could be used as a justification of the final model. If not, differential equations solution should be preferred, I guess. In our experience, analytical solution is usually pretty close to the differential equations but this may depend on the data (time step of records). One option to increase precision is to place extra EVID=2 records, so that the time step is smaller. Another option is to use MTIME for that, similar to:
>
> https://www.page-meeting.org/default.asp?abstract=1361
>
> Leonid
>
> On 12/19/2017 6:15 PM, Pavel Belo wrote:
>
> > Hello NONMEM Users,
> >
> > When clearance changes over time, the classic analytical solution for the 2-compartment linear model is not correct. Nevertheless, if the change is only ~30%, one can say it is still acceptable. Time required to run an analytical and numerical models is drastically different, which can be important for decision making. Did someone had an experience submitting using analytical solution when clearance changes over time to an agency or a journal? Can it be acceptable?
> >
> > Thanks,
> >
> > Paul
--
Nick Holford, Professor Clinical Pharmacology
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