NONMEM Users Network Archive

Hosted by Cognigen

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

From: Mats Karlsson <Mats.Karlsson_at_farmbio.uu.se>
Date: Fri, 11 Dec 2015 08:57:12 +0000

Nicolas,

The suggested error model comes from the reference below. It relaxes the st=
rong assumption that the residual error magnitude is the same for all subje=
cts. Such an assumption would be valid if assay error would be the dominati=
ng error, but it seldom is with clinical data.

Assumption testing in population pharmacokinetic models: illustrated with a=
n 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-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] On=
 Behalf Of SIMON Nicolas
Sent: Friday, December 11, 2015 8:24 AM
To: Andre Jackson; 'Leonid Gibiansky'; nmusers_at_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-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] D=
e la part de Andre Jackson Envoyé : jeudi 10 décembre 2015 21:22 À=
 : 'Leonid Gibiansky'; nmusers_at_globomaxnm.com Objet : RE: [NMusers] Err=
or in LSODA: Code -5

Leonid:

I tried the first suggestion by getting rid of some of the data that was d=
eficient (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 imp=
rove the analysis.

Thanks for your input.

Andre

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

Usually this error message is not informative: it just tells you that somet=
hing 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 out=
liers),
- starting with the better initial parameter values (e.g., your mean analys=
is 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 changin=
g the estimation method (try FO if nothing helps, and then used FO final es=
timates 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
>
> Jacksonan1945_at_Gmail.com <mailto:Jacksonan1945_at_Gmail.com>
>

Received on Fri Dec 11 2015 - 03:57:12 EST

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request_at_iconplc.com. Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.