RE: OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS
Dear Jules,
You are correct in pointing out where the problem lies.
However, the covariance matrix is not fine since it is at the boundary just as
much as the translation into correlation.
Correlation is calculated by this equation:
Cor(eta1,eta2)=OM1,2 /(sqrt(OM1,1)*sqrt(OM2,2))
Where:
OM1,1 and OM2,2, represents eta variance (as reported by nonmem output in the
OMEGA cov matrix, i.e. on var scale and not the sd scale that is reported in
the OMEGA corr matrix) and
OM1,2 represents Cov(eta1,eta2), i.e. as reported for the off diagonal on the
OMEGA cov matrix
I did not check your control stream thoroughly, but apparently, with the
current data and model baseline (E0) and Emax are completely correlated on the
individual level, maybe because of lack of information, maybe because of
physiology – you currently have an additive effect, but maybe Emax would be
bringing the PD endpoint all the way to zero or reducing the endpoint by a
certain fraction (i.e. a multiplicative model), or maybe healthy can not be
reduced at all, wheras elevated values can be reduced (almost) down to healthy
values? If you get that “structural” part of your drug-effects model right, you
may then be able to estimate correlation (or conclude with the new structure
these two etas are no longer correlated).
Best regards
Jakob
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Jules Heuberger
Sent: 17 September 2013 11:42
To: [email protected]
Subject: [NMusers] OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS
Dear NM Users,
I ran into a problem with a NM 7.2 run with an OMEGA BLOCK (2), receiving an
error message saying the parameter estimate is near its boundary (See also the
discussion in [NMusers] How to solve it? ERROR: PARAMETER ESTIMATE IS NEAR ITS
BOUNDARY ). After digging through the documentation I am still unsure where the
problem is originating from. What I figured out is that the problem lies in the
OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS *******, a matrix I believe is
only introduced since NM7.2. The estimate in this matrix that is giving
problems is the one for the OMEGA BLOCK, which is estimated to be 1 (a
boundary).
Now, as far as I know, the OMEGA - CORR MATRIX is related to the OMEGA - COV
MATRIX as the sqrt of its estimate. However, it is unclear to me how the OMEGA
BLOCK estimate (COV MATRIX), which gives the correlation between the two ETAs,
is related to the OMEGA - CORR MATRIX value. What does this value actually
mean, and what does it mean for my error message, as the correlation estimate
itself seems to be fine? In the print below you can see the model and resulting
estimates, the important ones being 5.26E-02 (OMEGA - COV MATRIX of ETA1-ETA2)
and 1.00E+00 (OMEGA - CORR MATRIX of ETA1-ETA2). The model has two ETAs and an
proportional error model,
Thanks in advance for any insights and help,
Best,
Jules Heuberger