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 <mailto:jacksonan1...@gmail.com> >
