Error in LSODA: Code -5

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 > > [email protected] <mailto:[email protected]>

De : [email protected] [mailto:[email protected]] De la part de Andre Jackson Envoyé : jeudi 10 décembre 2015 21:22 À : 'Leonid Gibiansky'; [email protected] 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:[email protected]] Sent: Thursday, December 10, 2015 9:59 AM To: Andre Jackson; [email protected] 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 > > [email protected] <mailto:[email protected]> >

-----Original Message----- From: [email protected] [mailto:[email protected]] On Behalf Of SIMON Nicolas Sent: Friday, December 11, 2015 8:24 AM To: Andre Jackson; 'Leonid Gibiansky'; [email protected] 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 : [email protected] [mailto:[email protected]] De la part de Andre Jackson Envoyé : jeudi 10 décembre 2015 21:22 À : 'Leonid Gibiansky'; [email protected] 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:[email protected]] Sent: Thursday, December 10, 2015 9:59 AM To: Andre Jackson; [email protected] 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 > > [email protected] <mailto:[email protected]> >

________________________________________ From: owner-nmusers_at_globomaxnm.com [owner-nmusers_at_globomaxnm.com] on behalf of Andre Jackson [jacksonan1945_at_gmail.com] Sent: Thursday, December 10, 2015 9:22 PM To: 'Leonid Gibiansky'; nmusers_at_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: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 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 > > Jacksonan1945_at_Gmail.com <mailto:Jacksonan1945_at_Gmail.com> >

________________________________________ From: [email protected] [[email protected]] on behalf of Andre Jackson [[email protected]] Sent: Thursday, December 10, 2015 9:22 PM To: 'Leonid Gibiansky'; [email protected] 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:[email protected]] Sent: Thursday, December 10, 2015 9:59 AM To: Andre Jackson; [email protected] 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 > > [email protected] <mailto:[email protected]> >

On 12/11/2015 9:40 AM, [email protected] 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: [email protected] [[email protected]] on behalf of > Andre Jackson [[email protected]] > Sent: Thursday, December 10, 2015 9:22 PM > To: 'Leonid Gibiansky'; [email protected] > 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:[email protected]] > Sent: Thursday, December 10, 2015 9:59 AM > To: Andre Jackson; [email protected] > 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 > > > > [email protected] <mailto:[email protected]>

-----Original Message----- From: [email protected] [mailto:[email protected]] Sent: Friday, December 11, 2015 9:40 AM To: [email protected]; [email protected]; [email protected] 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: [email protected] [[email protected]] on behalf of Andre Jackson [[email protected]] Sent: Thursday, December 10, 2015 9:22 PM To: 'Leonid Gibiansky'; [email protected] 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:[email protected]] Sent: Thursday, December 10, 2015 9:59 AM To: Andre Jackson; [email protected] 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 > > [email protected] <mailto:[email protected]> >