Re: Simulations with OMEGA BLOCK
Hi Andreas,
my understanding is that when you FIX a block, the whole block is fixed, you
can't fix only one element. So I guess it doesn't really matter where you put
the word FIX.
FIXED indicates that the entire block is constrained to be fixed
to its initial estimate.
Also, the block matrix is either all zeros and FIXED, or it must be positive
definite. If you fix one of the elements of the diagonal to 0, it goes against
these rules. Additionally, you can put zeros in the off-diagonal terms to form
a banded matrix, in which case, they will be assumed as fixed as well, without
using the word FIX.
My understanding is that NONMEM tries to see if there are zeros in the
off-diagonal terms and automatically assumes the block as banded (and even
diagonal) if possible.
The (entire) initial estimate of the block must be positive defi-
nite. The only exception is when the entire initial estimate of
the block is 0, in which case it must be fixed to this estimate.
Initial estimates of some of the elements of the block may be 0,
while initial estimates of some other elements may be nonzero,
but only in the case where the block is constrained to be of band
symmetric form. That is, given the diagonal and a group of con-
tiguous subdiagonals symmetrically ocurring across the diagonal,
the elements off both the diagonal and the subdiagonals are con-
strained to be zero. To specify the initial estimates of such a
block, the initial estimates of those elements that are to be
constrained to 0 should be given as 0, while all other initial
estimates should be given as nonzero. E.g., with these struc-
tures for $OMEGA BLOCK(3), the 0's are preserved:
x
0x
00x
x
xx
0xx
In your case, I think the only solution is to split into 2 separate blocks, but
maybe some guru will teach us otherwise.. :)
Out of curiosity, are you trying to simulate with a PRIOR? I ran into lots of
troubles when I had FIXED parameters in there, and after a lot of trying I just
gave up and removed them from the model.
I hope this helps.
Greetings from Cape Town,
Paolo
Quoted reply history
On 2013/10/08 10:22, Lindauer, A (Andreas) wrote:
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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Pharmacometrics Group
Division of Clinical Pharmacology
Department of Medicine
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