Hej, see example code below. Ina Frobel also applied an empirical hazard model (Frobel et al) to catch the pattern, see the model in DDMoRe model repository, with link to publication. http://repository.ddmore.foundation/model/DDMODEL00000065
$PROBLEM Time to first event data $SUBR ADVAN=13 TOL=9 $MODEL COMP=(HAZARD) $PK SIGM= THETA(1)*EXP(ETA(1)) MU=THETA(2) $DES DEL= 1E-12 TIM=T+DEL LNT = LOG(TIM) X1 =(LNT-MU)/SIGM PDF= EXP(-1/2*(X1**2))/SQRT(2*3.14159265) DADT(1)=1/(TIM*SIGM)*PDF/(1-PHI(X1)) $ERROR CHZ = A(1) SURX = EXP(-CHZ) DELX = 1E-12 TIMX=TIME+DELX LNTX = LOG(TIMX) X1X =(LNTX-MU)/SIGM PDFX= EXP(-1/2*(X1X**2))/SQRT(2*3.14159265) HAZNOW=1/(TIMX*SIGM)*PDFX/(1-PHI(X1X)) Y=SURX IF(DV.EQ.1) Y=SURX*HAZNOW $THETA (0,1) ;SIGMA ;1 SD of the log normal distribution $THETA (0) ;MU ;2 Mean of the log normal distribution $OMEGA 0 FIX ;OM1 ;1 ;Only to tell NONMEM that each ID has multiple rows $ESTIM MAXEVAL=9999 METHOD=0 LIKE SIGL=9 NSIG=3 PRINT=1 MSFO=msfb1 BR, Siv Siv Jönsson<http://katalog.uu.se/profile/?id=N96-5738>, PhD Researcher Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Sweden Phone: +46 (0)18 471 4315 Private: +46 (0)733 924 657 www.farmbio.uu.se/research/researchgroups/pharmacometrics/<http://www.farmbio.uu.se/research/researchgroups/pharmacometrics/> From: owner-nmus...@globomaxnm.com <owner-nmus...@globomaxnm.com> On Behalf Of Rik Schoemaker Sent: 29 August 2019 15:33 To: nmusers@globomaxnm.com Subject: [NMusers] Lognormal survival in NONMEM? Dear all, Playing with repeated time to event models, I run into the issue that simple diagnostics for a single time to event outcome suggest that constant hazard and Weibull models are not very appropriate. The lognormal model seems to provide a very nice fit; compared to a constant hazard, the hazard is suggested to be higher in the beginning and then significantly lower at later times. I have not seen any implementations online: does anyone know if the lognormal survival function can be implemented in NONMEM, and/or can anyone suggest alternative approaches? Some time-varying function to modify the hazard? Any and all suggestions appreciated! Kind regards, Rik Rik Schoemaker, PhD Occams Coöperatie U.A. Malandolaan 10 1187 HE Amstelveen The Netherlands www.occams.com<http://www.occams.com> +31 20 441 6410 rik.schoema...@occams.com<mailto:rik.schoema...@occams.com> [cid:image001.png@01D55E80.EB744C70] När du har kontakt med oss på Uppsala universitet med e-post så innebär det att vi behandlar dina personuppgifter. För att läsa mer om hur vi gör det kan du läsa här: http://www.uu.se/om-uu/dataskydd-personuppgifter/ E-mailing Uppsala University means that we will process your personal data. For more information on how this is performed, please read here: http://www.uu.se/en/about-uu/data-protection-policy
