Hello NMusers,
I have created a model that fit ok with FOCE+I. When I try to fit with SAEM, I
get the following error:
"""
ERROR IN TRANS4 ROUTINE: Q IS ZERO
Elapsed estimation time in seconds: 0.00
INDIVIDUAL OBJECTIVE FUNCTION VALUES ARE ALL ZERO. PROBLEM ENDED
"""
The data is very small, but the model seems acceptable from bootstrap on
FOCE+I. Any ideas are appreciated!
Thank you,
Omar
Omar Elashkar, B.Pharm, MSc
Graduate Assistant
University of Florida | College of Pharmacy
NONMEM Error on SAEM but not FOCEI
most likely, some type in the code. Can you provide the control stream?
Quoted reply history
On 1/26/2024 10:01 AM, Elashkar, Omar I. wrote:
> ERROR IN TRANS4 ROUTINE
Dear Omar,
What you describe is not that strange. It can happen because SAEM does random sampling whereas FOCE-I uses a directed search. Therefore extreme values can occur with SAEM. Please refer to the section I60 of user guide for v7+ "Stable Routines for Estimation Methods and Automated Protection Against Floating Point Exceptions" for more detail, but you could start with including
$ABBR PROTECT
which probably is adequate in your case.
Hope this helps,
Jeroen
http://pd-value.com
[email protected]
@PD_value
+31 6 23118438
-- More value out of your data!
Quoted reply history
On 26-01-2024 16:01, Elashkar, Omar I. wrote:
> Hello NMusers,
>
> I have created a model that fit ok with FOCE+I. When I try to fit with SAEM, I get the following error:
>
> """
> ERROR IN TRANS4 ROUTINE: Q IS ZERO
> Elapsed estimation time in seconds: 0.00
> INDIVIDUAL OBJECTIVE FUNCTION VALUES ARE ALL ZERO. PROBLEM ENDED
> """
>
> The data is very small, but the model seems acceptable from bootstrap on FOCE+I. Any ideas are appreciated!
>
> Thank you,
> Omar
>
> *Omar Elashkar, *B.Pharm, MSc
>
> Graduate Assistant
>
> University of Florida | College of Pharmacy
An interesting undocumented feature of PROTECT. If you have EXP(0), e.g.,
KA = TVKA *EXP(0)
The fortran translation in this case apparently is:
KA=TVKA*PEXP(*)B000092
Which then throws a syntax error.
Doesn't happen without
$ABBR PROTECT
Not sure if that counts as a bug, but does prohibit using PROTECT in automated
methods to run models with/without BSV, or at least makes it a little more
difficult.
Mark Sale M.D.
Vice President
Integrated Drug Development
[email protected]
Remote-Forestville CA
Office Hours 9 AM - 5 PM Eastern Time
+1 302-516-1684
www.certara.com
Quoted reply history
-----Original Message-----
From: [email protected] <[email protected]> On Behalf Of
Leonid Gibiansky
Sent: Friday, January 26, 2024 7:42 AM
To: Jeroen Elassaiss-Schaap (PD-value B.V.) <[email protected]>; Elashkar,
Omar I. <[email protected]>; [email protected]
Subject: Re: [NMusers] NONMEM Error on SAEM but not FOCEI
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This part is easy to solve: if you do it in log space, Q will always be
positive, no PROTECT is needed (and I am not sure it is relevant in the case
when Q is going to be negative).
On 1/26/2024 10:27 AM, Jeroen Elassaiss-Schaap (PD-value B.V.) wrote:
> Dear Omar,
>
>
> What you describe is not that strange. It can happen because SAEM does
> random sampling whereas FOCE-I uses a directed search. Therefore
> extreme values can occur with SAEM. Please refer to the section I60 of
> user guide for v7+ "Stable Routines for Estimation Methods and
> Automated Protection Against Floating Point Exceptions" for more
> detail, but you could start with including
>
> $ABBR PROTECT
>
> which probably is adequate in your case.
>
>
> Hope this helps,
>
> Jeroen
>
>
> https://nam11.safelinks.protection.outlook.com/?url=http%3A%2F%2Fpd-va
> lue.com%2F&data=05%7C02%7CMark.sale%40Certara.com%7Cecb21da5ca6e4a50d8
> b308dc1e865d9a%7C7287abd30220456e98514352bae208c9%7C1%7C0%7C6384188096
> 75762447%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiL
> CJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=4uyLVZH1Zx4EWEQws7xn4
> %2FKR%2BeFIro5ul10iI6LMUM4%3D&reserved=0
> [email protected]
> @PD_value
> +31 6 23118438
> -- More value out of your data!
>
> On 26-01-2024 16:01, Elashkar, Omar I. wrote:
>> Hello NMusers,
>>
>> I have created a model that fit ok with FOCE+I. When I try to fit
>> with SAEM, I get the following error:
>>
>> """
>> ERROR IN TRANS4 ROUTINE: Q IS ZERO
>> Elapsed estimation time in seconds: 0.00
>> INDIVIDUAL OBJECTIVE FUNCTION VALUES ARE ALL ZERO. PROBLEM ENDED """
>>
>> The data is very small, but the model seems acceptable from bootstrap
>> on FOCE+I. Any ideas are appreciated!
>>
>> Thank you,
>> Omar
>>
>>
>>
>> *Omar Elashkar, *B.Pharm, MSc
>>
>> Graduate Assistant
>>
>> University of Florida | College of Pharmacy
>>
>>
>>
>
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Clearly a bug in the $ABBR PROTECT processor. The NMTRAN interpreter removes
the *EXP(0) (because it does not modify the equation), which messes up $ABBR
PROTECT process. This occurs only with EXP(0), but not EXP(1) EXP(2), etc.
Work-arounds are:
KA = TVKA *EXP(-0)
or
ZERO=0.0
KA = TVKA *EXP(ZERO)
Robert J. Bauer, Ph.D.
Senior Director
Pharmacometrics R&D
ICON Early Phase
731 Arbor way, suite 100
Blue Bell, PA 19422
Office: (215) 616-6428
Mobile: (925) 286-0769
[email protected]<mailto:[email protected]>
http://www.iconplc.com/
Quoted reply history
From: [email protected]<mailto:[email protected]>
<[email protected]<mailto:[email protected]>> On Behalf
Of Mark Sale
Sent: Friday, January 26, 2024 10:59 AM
To: Leonid Gibiansky
<[email protected]<mailto:[email protected]>>; Jeroen
Elassaiss-Schaap (PD-value B.V.)
<[email protected]<mailto:[email protected]>>; Elashkar, Omar I.
<[email protected]<mailto:[email protected]>>;
[email protected]<mailto:[email protected]>
Subject: [EXTERNAL] RE: [NMusers] NONMEM Error on SAEM but not FOCEI
An interesting undocumented feature of PROTECT. If you have EXP(0), e.g.,
KA = TVKA *EXP(0)
The fortran translation in this case apparently is:
KA=TVKA*PEXP(*)B000092
Which then throws a syntax error.
Doesn't happen without
$ABBR PROTECT
Not sure if that counts as a bug, but does prohibit using PROTECT in automated
methods to run models with/without BSV, or at least makes it a little more
difficult.
Mark Sale M.D.
Vice President
Integrated Drug Development
[email protected]<mailto:[email protected]>
Remote-Forestville CA
Office Hours 9 AM - 5 PM Eastern Time
+1 302-516-1684
http://www.certara.com