Yes, SIGMA should be fixed to 1 (do not try anything else, it has to be
done correctly in the code first, and then we should worry about how to
make it work)
For combined error, expression is
W = SQRT(W1**2 + W2**2) (squares in both terms)
Do not worry about error 134, this is harmless, and you can fix it any
time after you get your model right. Add UNCONDITIONAL MATRIX=S to the
$COV step.
For PARAMETER ESTIMATE IS NEAR ITS BOUNDARY try to add
NOSIGMABOUNDTEST NOOMEGABOUNDTEST NOTHETABOUNDTEST
to $est record
Most of the time, numerical difficulties come from the problems with the
data, so it makes sense to clean the data set first as much as possible.
Leonid
On 5/26/2023 9:30 AM, Hiba Sliem wrote:
Hi
I already tried fixing the value of sigma to 1, the covariance step isn't
implemented when I do that.
If I try fixing it to 0.144 the minimization isn't successful.
I also tried a combined error model like this:
LOQ=0.1
IPRED = F
W1 = THETA(8)*IPRED
W2 = THETA(9)
W = SQRT(W1**1 + W2**2)
DEL = 0
IF(W.EQ.0) DEL = 1
IRES = DV - IPRED
IWRES = IRES/(W + DEL)
DUM = (LOQ -IPRED)/(W + DEL)
CUMD = PHI(DUM)
IF(BLQ.EQ.0) THEN
F_FLAG=0
Y= IPRED +W*ERR(1)
ELSE
F_FLAG=1
Y=CUMD
MDVRES = 1
ENDIF
In which case I get a PARAMETER ESTIMATE IS NEAR ITS BOUNDARY error message
When trying to fix Sigma in the combined model I have a MINIMIZATION TERMINATED
DUE TO ROUNDING ERRORS (ERROR=134) message.
My dataset has a lot of predose samples and washouts between different periods,
is it possible the issue comes from my dataset?
Regards
-----Original Message-----
From: Leonid Gibiansky <lgibian...@quantpharm.com>
Sent: Friday, 26 May 2023 14:51
To: Hiba Sliem <hiba.sl...@pharmalex.com>; nmusers@globomaxnm.com
Subject: Re: [NMusers] Problem with estimating sigma when using M3 method
[You don't often get email from lgibian...@quantpharm.com. Learn why this is
important at https://aka.ms/LearnAboutSenderIdentification ]
you should fix
$SIGMA
1 FIX
as you are already estimating the SD using THETA(8).
Leonid
On 5/26/2023 4:57 AM, Hiba Sliem wrote:
Hello
I'm fairly new to nonmem, I'm currently trying to model a phase 1
study with BLQ values, while the run was successful with no error message, my
residual error has a %rse >70 and a confidence interval that includes
zero.
Here's my code:
$ERROR
LOQ=0.1
IPRED = F
SD = THETA(8)*IPRED
DEL = 0
IF(SD.EQ.0) DEL = 1
IRES = DV - IPRED
IWRES = IRES / (SD + DEL)
DUM = (LOQ -IPRED) / (SD + DEL)
CUMD = PHI(DUM) + DEL
IF(BLQ.EQ.0) THEN
F_FLAG=0
Y= IPRED +SD*ERR(1)
ELSE
F_FLAG=1
Y=CUMD
MDVRES = 1
ENDIF
$EST METHOD=1 INTERACTION LAPLACIAN PRINT=5 MAX=9999 SIG=3 SLOW
NUMERICAL MSFO=*.msf
$SIGMA
0.38 ;[P] sigma(1,1) (estimated in a previous model)
Furthermore, when trying to fit this model to my phase 2 dataset,
covariance step fails when I implement it.
Any suggestions are welcome
Thank you
