RE: [NMusers] Error in LSODA: Code -5

2015-12-11 Thread Mats Karlsson 
Nicolas,

The suggested error model comes from the reference below. It relaxes the strong 
assumption that the residual error magnitude is the same for all subjects. Such 
an assumption would be valid if assay error would be the dominating error, but 
it seldom is with clinical data.

Assumption testing in population pharmacokinetic models: illustrated with an 
analysis of moxonidine data from congestive heart failure patients.
Karlsson MO, Jonsson EN, Wiltse CG, Wade JR.
J Pharmacokinet Biopharm. 1998 Apr;26(2):207-46.

Best regards,
Mats
Mats Karlsson, PhD
Professor of Pharmacometrics
 
Dept of Pharmaceutical Biosciences
Faculty of Pharmacy
Uppsala University
Box 591
75124 Uppsala
 
Phone: +46 18 4714105
Fax + 46 18 4714003
www.farmbio.uu.se/research/researchgroups/pharmacometrics/


-Original Message-
From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On 
Behalf Of SIMON Nicolas
Sent: Friday, December 11, 2015 8:24 AM
To: Andre Jackson; 'Leonid Gibiansky'; nmusers@globomaxnm.com
Subject: RE: [NMusers] Error in LSODA: Code -5

Leonid,

You suggest the following residual model:

Y=IPRED*(1+W*EXP(ETA())*EPS())

Could you give more information on it?

Best regards
Nicolas


-Message d'origine-
De : owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] De la 
part de Andre Jackson Envoyé : jeudi 10 décembre 2015 21:22 À : 'Leonid 
Gibiansky'; nmusers@globomaxnm.com Objet : RE: [NMusers] Error in LSODA: Code -5

Leonid:

I tried the first suggestion by getting rid of  some of the data that was 
deficient (i.e., subjects with less than 8 concentrations over the 30 hr.
sampling period)  and the LSODA error was not present.   

I will also try your other suggestions sequentially to see if they also improve 
the analysis.

Thanks for your input.

Andre

-Original Message-
From: Leonid Gibiansky [mailto:lgibian...@quantpharm.com]
Sent: Thursday, December 10, 2015 9:59 AM
To: Andre Jackson; nmusers@globomaxnm.com
Subject: Re: [NMusers] Error in LSODA: Code -5

Usually this error message is not informative: it just tells you that something 
is wrong with the model. It can be fixed by (in the order of
importance)
- cleaning the data (look on concentration-time plots to remove obvious 
outliers),
- starting with the better initial parameter values (e.g., your mean analysis 
final estimates),
- setting bounds on THETAs,
- removing some ETAs,
- using combined residual error instead of the purely proportional one,
- using residual error with ETAs (instead of Y=IPRED*(1+W*EPS()) use 
Y=IPRED(1+W*EXP(ETA())*EPS()),
- other model modifications/simplifications/improvements, including changing 
the estimation method (try FO if nothing helps, and then used FO final 
estimates to start something more advanced)

Leonid



--
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web:www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel:(301) 767 5566



On 12/10/2015 8:10 AM, Andre Jackson wrote:
> I have run a control stream that runs okay following MU modeling with 
> the mean data to establish the  best structural model using NM7 with 
> ADVAN 13  TRANS1 TOL=6.
>
> However when I attempt to run the model in a population mode with even 
> one eta on a MU I get the following error.
>
> OCCURS DURING SEARCH FOR ETA AT INITIAL VALUE, ETA=0
>
> ERROR IN LSODA: CODE  -5
>
>   ERROR OCURRED WHILE ATTEMPTING TO OBTAIN INITIAL VALUES FOR ATOL
>
> 0PROGRAM TERMINATED BY OBJ
>
> I have seen some posts in the archives on LSODA and differential 
> equations but nothing that seems to address my problem directly.
>
> Does anyone know of any more definitive posts or have suggestions as 
> to how best to proceed.
>
> Thanks
>
> Andre Jackson
>
> jacksonan1...@gmail.com 
>

[NMusers] Mark Your Calendars! Hold the Dates! ICON NONMEM/PDxPoP Workshops for 2016

2015-12-11 Thread Wilhelm-Lear, Lisa 
The following workshops have been scheduled for 2016:

March 1-3 – San Francisco, California – 3-day NONMEM/PDxPoP Workshop
Location:  Doubletree by Hilton San Francisco Airport, 835 Airport Boulevard, 
Burlingame, CA  94010 (just 10 minutes from the airport!)

March 4 – San Francisco, California – TMDD Workshop presented by Leonid and 
Ekaterina Gibiansky of QuantPharm LLC
Location:  Doubletree by Hilton San Francisco Airport, 835 Airport Boulevard, 
Burlingame, CA  94010 (just 10 minutes from the airport!)

April 12-14 – Howard County Maryland – 3-day NONMEM/PDxPoP Workshop

June 5 – 1 Day Advanced Methods NONMEM workshop – PAGE 2016 – Lisbon, Portugal

September 13-15 – Howard County Maryland – 3-day NONMEM/PDxPoP Workshop

October 22 – 1 Day Advanced Methods NONMEM Workshop – ACoP 2016 – Seattle, 
Washington

The workshops are not yet on our website for registration but if you are 
interested in any of the dates listed or have questions about the workshops, 
please contact me at:  lisa.wilh...@iconplc.com

Kind regards,



Lisa R. Wilhelm-Lear
Customer Service Lead
NONMEM / PDxPoP Software

Phone:  301-944-6771
Fax: 215-789-9549
www.iconplc.com




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Thank You,

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Registered number: 145835

[NMusers] Error in $NONPARAMETRIC

2015-12-11 Thread R.terHeine 
Dear all,

When generating a VPC for a nonparametric ($NONPARAMETRIC subroutine on) model, 
I get the following error message from NONMEM 7.3.0 (installed on OSX 10.10.5, 
PsN 4.4.8), which doesn't occur with creating a VPC for a "normal" parametric 
model.

> “ #TERE:
> 0ERROR IN READING FILE : FILE15/16 USED BY DAT4 “

The control stream that causes this error is just a MAXEVAL=0 to filter the 
original data on IGNORE/ACCEPT and output needed variables defined in the model 
code, so it should not be a difficult task for NONMEM.

Does anyone know what might be the cause of this error?

Sincerely,
Rob
Het Radboudumc staat geregistreerd bij de Kamer van Koophandel in het 
handelsregister onder nummer 41055629.
The Radboud university medical center is listed in the Commercial Register of 
the Chamber of Commerce under file number 41055629.

RE: [NMusers] Error in LSODA: Code -5

2015-12-11 Thread E.Olofsen 
Usually tolerance criteria for ODE solvers apply to the solution at the end of 
an integration interval.  In that case, there is a difference between the 
solution at some time instant if it is preceded by an observation record with 
MDV=1 or not.  So the tolerance settings for ADVAN13 which are ok for the 
"normal" subjects could be problematic for the "deficient" subjects if an 
integration interval gets too large.  So perhaps adding missing observation 
records in between could help preventing LSODA errors.

Erik

From: owner-nmus...@globomaxnm.com [owner-nmus...@globomaxnm.com] on behalf of 
Andre Jackson [jacksonan1...@gmail.com]
Sent: Thursday, December 10, 2015 9:22 PM
To: 'Leonid Gibiansky'; nmusers@globomaxnm.com
Subject: RE: [NMusers] Error in LSODA: Code -5

Leonid:

I tried the first suggestion by getting rid of  some of the data that was
deficient (i.e., subjects with less than 8 concentrations over the 30 hr.
sampling period)  and the LSODA error was not present.

I will also try your other suggestions sequentially to see if they also
improve the analysis.

Thanks for your input.

Andre

-Original Message-
From: Leonid Gibiansky [mailto:lgibian...@quantpharm.com]
Sent: Thursday, December 10, 2015 9:59 AM
To: Andre Jackson; nmusers@globomaxnm.com
Subject: Re: [NMusers] Error in LSODA: Code -5

Usually this error message is not informative: it just tells you that
something is wrong with the model. It can be fixed by (in the order of
importance)
- cleaning the data (look on concentration-time plots to remove obvious
outliers),
- starting with the better initial parameter values (e.g., your mean
analysis final estimates),
- setting bounds on THETAs,
- removing some ETAs,
- using combined residual error instead of the purely proportional one,
- using residual error with ETAs (instead of Y=IPRED*(1+W*EPS()) use
Y=IPRED(1+W*EXP(ETA())*EPS()),
- other model modifications/simplifications/improvements, including changing
the estimation method (try FO if nothing helps, and then used FO final
estimates to start something more advanced)

Leonid



--
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web:www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel:(301) 767 5566



On 12/10/2015 8:10 AM, Andre Jackson wrote:
> I have run a control stream that runs okay following MU modeling with
> the mean data to establish the  best structural model using NM7 with
> ADVAN 13  TRANS1 TOL=6.
>
> However when I attempt to run the model in a population mode with even
> one eta on a MU I get the following error.
>
> OCCURS DURING SEARCH FOR ETA AT INITIAL VALUE, ETA=0
>
> ERROR IN LSODA: CODE  -5
>
>   ERROR OCURRED WHILE ATTEMPTING TO OBTAIN INITIAL VALUES FOR ATOL
>
> 0PROGRAM TERMINATED BY OBJ
>
> I have seen some posts in the archives on LSODA and differential
> equations but nothing that seems to address my problem directly.
>
> Does anyone know of any more definitive posts or have suggestions as to
> how best to proceed.
>
> Thanks
>
> Andre Jackson
>
> jacksonan1...@gmail.com 
>

Re: [NMusers] Error in LSODA: Code -5

2015-12-11 Thread Leonid Gibiansky 
Setting lower TOL values (as low as 2-3-4) may help as well (but it 
should be done carefully as there are examples where TOL=4 solution was 
different from TOL=9 solution; so if this helps, TOL should be increased 
back to 7-8-9 later in the modeling process when the more stable model 
is found)

Leonid


--
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web:www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel:(301) 767 5566



On 12/11/2015 9:40 AM, e.olof...@lumc.nl wrote:

Usually tolerance criteria for ODE solvers apply to the solution at the end of an integration 
interval.  In that case, there is a difference between the solution at some time instant if it is 
preceded by an observation record with MDV=1 or not.  So the tolerance settings for ADVAN13 which 
are ok for the "normal" subjects could be problematic for the "deficient" 
subjects if an integration interval gets too large.  So perhaps adding missing observation records 
in between could help preventing LSODA errors.

Erik

From: owner-nmus...@globomaxnm.com [owner-nmus...@globomaxnm.com] on behalf of 
Andre Jackson [jacksonan1...@gmail.com]
Sent: Thursday, December 10, 2015 9:22 PM
To: 'Leonid Gibiansky'; nmusers@globomaxnm.com
Subject: RE: [NMusers] Error in LSODA: Code -5

Leonid:

I tried the first suggestion by getting rid of  some of the data that was
deficient (i.e., subjects with less than 8 concentrations over the 30 hr.
sampling period)  and the LSODA error was not present.

I will also try your other suggestions sequentially to see if they also
improve the analysis.

Thanks for your input.

Andre

-Original Message-
From: Leonid Gibiansky [mailto:lgibian...@quantpharm.com]
Sent: Thursday, December 10, 2015 9:59 AM
To: Andre Jackson; nmusers@globomaxnm.com
Subject: Re: [NMusers] Error in LSODA: Code -5

Usually this error message is not informative: it just tells you that
something is wrong with the model. It can be fixed by (in the order of
importance)
- cleaning the data (look on concentration-time plots to remove obvious
outliers),
- starting with the better initial parameter values (e.g., your mean
analysis final estimates),
- setting bounds on THETAs,
- removing some ETAs,
- using combined residual error instead of the purely proportional one,
- using residual error with ETAs (instead of Y=IPRED*(1+W*EPS()) use
Y=IPRED(1+W*EXP(ETA())*EPS()),
- other model modifications/simplifications/improvements, including changing
the estimation method (try FO if nothing helps, and then used FO final
estimates to start something more advanced)

Leonid



--
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web:www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel:(301) 767 5566



On 12/10/2015 8:10 AM, Andre Jackson wrote:

I have run a control stream that runs okay following MU modeling with
the mean data to establish the  best structural model using NM7 with
ADVAN 13  TRANS1 TOL=6.

However when I attempt to run the model in a population mode with even
one eta on a MU I get the following error.

OCCURS DURING SEARCH FOR ETA AT INITIAL VALUE, ETA=0

ERROR IN LSODA: CODE  -5

   ERROR OCURRED WHILE ATTEMPTING TO OBTAIN INITIAL VALUES FOR ATOL

0PROGRAM TERMINATED BY OBJ

I have seen some posts in the archives on LSODA and differential
equations but nothing that seems to address my problem directly.

Does anyone know of any more definitive posts or have suggestions as to
how best to proceed.

Thanks

Andre Jackson

jacksonan1...@gmail.com

RE: [NMusers] Error in LSODA: Code -5

2015-12-11 Thread Andre Jackson 
Eric:

I revisited my data set and indeed I do have MDV=1 values in between values
with a positive DV  due to the fact that I am generating data for
compartments where there are no observations.  Oftentimes also a measured
concentration within the sampled compartment had the next time point DV
missing so it was set to MDV=1.

-Original Message-
From: e.olof...@lumc.nl [mailto:e.olof...@lumc.nl] 
Sent: Friday, December 11, 2015 9:40 AM
To: jacksonan1...@gmail.com; lgibian...@quantpharm.com;
nmusers@globomaxnm.com
Subject: RE: [NMusers] Error in LSODA: Code -5

Usually tolerance criteria for ODE solvers apply to the solution at the end
of an integration interval.  In that case, there is a difference between the
solution at some time instant if it is preceded by an observation record
with MDV=1 or not.  So the tolerance settings for ADVAN13 which are ok for
the "normal" subjects could be problematic for the "deficient" subjects if
an integration interval gets too large.  So perhaps adding missing
observation records in between could help preventing LSODA errors.

Erik

From: owner-nmus...@globomaxnm.com [owner-nmus...@globomaxnm.com] on behalf
of Andre Jackson [jacksonan1...@gmail.com]
Sent: Thursday, December 10, 2015 9:22 PM
To: 'Leonid Gibiansky'; nmusers@globomaxnm.com
Subject: RE: [NMusers] Error in LSODA: Code -5

Leonid:

I tried the first suggestion by getting rid of  some of the data that was
deficient (i.e., subjects with less than 8 concentrations over the 30 hr.
sampling period)  and the LSODA error was not present.

I will also try your other suggestions sequentially to see if they also
improve the analysis.

Thanks for your input.

Andre

-Original Message-
From: Leonid Gibiansky [mailto:lgibian...@quantpharm.com]
Sent: Thursday, December 10, 2015 9:59 AM
To: Andre Jackson; nmusers@globomaxnm.com
Subject: Re: [NMusers] Error in LSODA: Code -5

Usually this error message is not informative: it just tells you that
something is wrong with the model. It can be fixed by (in the order of
importance)
- cleaning the data (look on concentration-time plots to remove obvious
outliers),
- starting with the better initial parameter values (e.g., your mean
analysis final estimates),
- setting bounds on THETAs,
- removing some ETAs,
- using combined residual error instead of the purely proportional one,
- using residual error with ETAs (instead of Y=IPRED*(1+W*EPS()) use
Y=IPRED(1+W*EXP(ETA())*EPS()),
- other model modifications/simplifications/improvements, including changing
the estimation method (try FO if nothing helps, and then used FO final
estimates to start something more advanced)

Leonid



--
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web:www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel:(301) 767 5566



On 12/10/2015 8:10 AM, Andre Jackson wrote:
> I have run a control stream that runs okay following MU modeling with 
> the mean data to establish the  best structural model using NM7 with 
> ADVAN 13  TRANS1 TOL=6.
>
> However when I attempt to run the model in a population mode with even 
> one eta on a MU I get the following error.
>
> OCCURS DURING SEARCH FOR ETA AT INITIAL VALUE, ETA=0
>
> ERROR IN LSODA: CODE  -5
>
>   ERROR OCURRED WHILE ATTEMPTING TO OBTAIN INITIAL VALUES FOR ATOL
>
> 0PROGRAM TERMINATED BY OBJ
>
> I have seen some posts in the archives on LSODA and differential 
> equations but nothing that seems to address my problem directly.
>
> Does anyone know of any more definitive posts or have suggestions as 
> to how best to proceed.
>
> Thanks
>
> Andre Jackson
>
> jacksonan1...@gmail.com 
>

[NMusers] DDMoRe launches a new platform

2015-12-11 Thread Mats Karlsson 
Please find a press release at the site below describing the features of a new 
platform aiming to advance quantitative drug development.

http://www.ddmore.eu/sites/ddmore/files/DDMoRe%20press%20release%20Dec%202015.pdf

on behalf of colleagues from the DDMoRe project