RE: Simulations with OMEGA BLOCK
Hi Andreas,
You cant fix part of a block in NONMEM, you have to fix the whole block. So the
trick is to construct the covaiance matrix structure you want out of smaller
blocks.
And when you fix an ETA on the diagonal to zero the corresponding covariances
have to be zero as well. (i.e. the left-most variables in you BLOCK(8) matrix)
So what I think you want for your full-matrix is something like:
$OMEGA
0 FIX ; IIV_CL2
$OMEGA BLOCK(7)
0.1 ; IIV_V2
0 0.1 ; IIV_F1
0 0 0.01 ; IIV_KA
0 0 0 0.01 ; IOV_KA
0 0 0 0 0.01
0 0 0 0 0 0.01
0 0 0 0 0 0 0.01
I hope you have LOTS of data since a BLOCK(7) marix has LOTS of paramaters to
estimate.
You are also combining IIV and IOV variances in a single matrix.
Does it make sense to expect the IIV_KA and IOV_KA to be correlated?
I cant imagine how this is supposed to work, but admittedly I havent given it
all that much thought.
It just looks fishy to me. I cant seem to understand what behavior you are
trying to capture in this kind of covariance structure.
warm regards,
Douglas Eleveld
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Quoted reply history
Van: [email protected] [mailto:[email protected]] Namens
Lindauer, A (Andreas)
Verzonden: October 8, 2013 10:22 AM
Aan: [email protected]
Onderwerp: [NMusers] Simulations with OMEGA BLOCK
Hi NMUSERS,
I have a question regarding the use of OMEGA BLOCK statements in simulations
when one (or more) elements of the matrix are 0.
When I use the following lines to describe the OMEGA structure and run the
simulation everything works well:
$OMEGA
0 FIX ; IIV_CL2
0.1 ; IIV_V2
0.1 ; IIV_F1
0.01 ; IIV_KA
$OMEGA BLOCK(1) 0.01 ; IOV_KA
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
However, rewriting the above as a full matrix gives me an error message:
$OMEGA BLOCK(8)
0 FIX
0 0.1
0 0 0.1
0 0 0 0.01
0 0 0 0 0.01
0 0 0 0 0 0.01
0 0 0 0 0 0 0.01
0 0 0 0 0 0 0 0.01
NM-TRAN MESSAGES
AN ERROR WAS FOUND IN THE CONTROL STATEMENTS.
AN ERROR WAS FOUND ON LINE 75 AT THE APPROXIMATE POSITION NOTED:
0 0 0 0 0 0 0 0.01
224 A VARIANCE IS ZERO, BUT THE BLOCK IS NOT FIXED TO ZERO.
I tried numerous different ways of placing the term FIX in the block, or not
mentioning it at all - nothing worked, except replacing the 0 diagonal element
by a very small number. I know that there are certain constrains of using 0
values in an OMEGA BLOCK (band symmetric form), but I always thought this was
only relevant for estimation.
Has anyone come across a similar issue when simulating?
Best regards, Andreas.
Andreas Lindauer, Ph.D.
Associate Principal Scientist, Clinical PKPD
Pharmacokinetics, Pharmacodynamics, and Drug Metabolism
Merck & Co. / MSD
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