Dear Laureen,
I recommend that you determine with exploratory plotting how strong the
evidence for the 3-compartment behavior is (eg. in semi-log plots: is 3 cpt
behavior present in most subjects? are inflection points reasonably collocated?
how do slope changes relate to measurement noise? etc.).
If you do see strong evidence for 3 cpt behavior and have a biological
rationale for a third compartment, I wouldn't just drop the 3 cpt model
because of a high condition number in the model you tested, especially since
you said that precision did not deteriorate.
The fact that the 2 cpt model was borderline ill-conditioned (998 ~ 1000) with
serially sampled IV data suggests that the 2 cpt model was already
over-parameterized. My recommendation is to simplify the 2 cpt model (eg. by
simplifying random structure, looking for large entries in correlation matrix
or RSEs, ...) and then run the comparison again.
Herbert
From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On
Behalf Of Denney, William S.
Sent: Thursday, March 24, 2016 6:53 AM
To: L.A. ten Berg - Lammers; 'nmusers@globomaxnm.com'
Subject: [NMusers] RE: nonmem question regarding condition number
EXTERNAL
Hi Laureen,
Large condition numbers (typically interpreted as >1000) indicate that two or
more parameters in the model are highly correlated in their covariance and that
the model parameters are difficult to identify. Given your description below,
I would not suggest using the 3-compartment model (even with its 180 point
reduction in OFV) because two of your parameters are so highly correlated that
the condition number is reaching the level of computational precision (2E16 is
very large for a condition number). I'd also look at the NONMEM output to see
if the 3-compartment model had any errors around the convergence.
Thanks,
Bill
From: owner-nmus...@globomaxnm.com<mailto:owner-nmus...@globomaxnm.com>
[mailto:owner-nmus...@globomaxnm.com] On Behalf Of L.A. ten Berg - Lammers
Sent: Thursday, March 24, 2016 6:10 AM
To: 'nmusers@globomaxnm.com'
Subject: [NMusers] nonmem question regarding condition number
Dear nmusers,
I am currently analyzing PK profiles after a single iv adminstration.
Volunteers were sampled frequently: 12 samples per curve.
For the structural model 2- and a 3-compartment models are compared. The CWRES
vs time plot of the 2-compartment shows the typical wave, indicative for a
3-compartment model. Introduction of a third compartment eliminated the wave,
OFV decreased with 180 points, precision of the estimates did change notably,
but the condition number increased from 998 to 2.0*E16.
Does anyone know how to interpret this large increase in condition number?
Best wishes,
Laureen ten Berg
[Beschrijving: cid:image001.gif@01CD804B.C9EE1BA0]
Laureen ten Berg-Lammers
Hospital Pharmacist
Academisch Medisch Centrum
Universiteit van Amsterdam
Meibergdreef 9 | 1105 AZ Amsterdam | Room: M01-224
Tel: +31(0)20-5662726 | Pager *62726 |
l.a.tenberg-lamm...@uva.amc.nl<mailto:l.a.tenberg-lamm...@uva.amc.nl>
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