RE: [NMusers] NonMem and EVID=2

From: Bill Denney <wdenney_at_humanpredictions.com>
Date: Tue, 23 Apr 2019 15:15:28 -0400

Hi Johan,



Since I answered the original message, I’ll respond here, too, thou=
gh with
a less specific answer at this point. If you could provide the control
stream and data (or example of the data), that would help.



My guess is generally similar to my guess in 2016. The integration steps
could be too long and the problem too stiff without the EVID=2 rows.
Usually, this is automatically detected by the integrator, but if there is
a major change in the problem dynamics (e.g. TMDD), the EVID=2 rows could
assist the integrator with an intermediate step. This may show up in the
covariance step because the maximum likelihood estimate has good
convergence properties, but nearby there is a space that has poor
properties (such as the TMDD behavior changing significantly). This could
also occur if you do not have bounds on parameters that require bounds
(such as a linear estimate of clearance which is not restricted to be > 0).



For a more specific answer, I think that I’d need to see the code a=
nd data.



Thanks,



Bill



*From:* owner-nmusers_at_globomaxnm.com <owner-nmusers_at_globomaxnm.com> *On
Behalf Of *Johan Rosenborg
*Sent:* Tuesday, April 23, 2019 11:33 AM
*To:* nmusers_at_globomaxnm.com
*Subject:* [NMusers] NonMem and EVID=2



Hello everybody,

In order to obtain predicted values in a PopPK analysis without covariates
at points in time with no actual values I have inserted extra rows
indicated with EVID=2. The covariance step is completed when including
these extra rows and precision of the parameter estimates are adequate.
When omitting the extra rows {IGNORE=(EVID.EQ.2)}, I get exactly the same
parameter estimates, the covariace step can be completed with some
difficulty, but precision of the parameter estimates are now inadequate. I
use METHOD=1 and just like Ahmed Abbas Suleiman experienced (
https://cognigencorp.com/nonmem/current/2013-February/4440.html 2
<https://cognigencorp.com/nonmem/current/2013-February/4440.html>), my
outcome did not differ between the two conditions when setting METHOD=0. =
I
saw that William Denney has responded to a similar question in 2016 (
https://cognigencorp.com/nonmem/current/2016-February/6085.html 2
<https://cognigencorp.com/nonmem/current/2016-February/6085.html>).

I cannot see any response to Ahmed’s comment; do you Bill or somebo=
dy else
have any idea why the outcomes differ with METHOD=1 but not with METHOD=
=0
in NonMem when including extra rows in the data set?

Thank you in advance and kind regards,

Johan


Received on Tue Apr 23 2019 - 15:15:28 EDT

This archive was generated by hypermail 2.3.0 : Fri Sep 27 2019 - 17:04:36 EDT