RE: Lognormal survival in NONMEM?
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 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 MAXEVAL99 METHOD=0 LIKE SIGL=9 NSIG=3 PRINT=1 MSFO=msfb1
BR, Siv
Siv 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
http://www.farmbio.uu.se/research/researchgroups/pharmacometrics/
Quoted reply history
From: owner-nmusers_at_globomaxnm.com <owner-nmusers_at_globomaxnm.com> On Behalf Of Rik Schoemaker
Sent: 29 August 2019 15:33
To: nmusers_at_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 Coperatie U.A.
Malandolaan 10
1187 HE Amstelveen
The Netherlands
http://www.occams.com
+31 20 441 6410
rik.schoemaker_at_occams.com<mailto:rik.schoemaker_at_occams.com>
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