[NMusers] RE: Lognormal survival in NONMEM?

From: Siv Jönsson <Siv.Jonsson_at_farmbio.uu.se>
Date: Thu, 29 Aug 2019 14:03:18 +0000

Hej, see example code below.

Ina Frobel also applied an empirical hazard model (Frobel et al) to catch t=
he pattern, see the model in DDMoRe model repository, with link to publicat=
ion.
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=ms=
fb1


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.farmb=
io.uu.se/research/researchgroups/pharmacometrics/>

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 simpl=
e diagnostics for a single time to event outcome suggest that constant haza=
rd and Weibull models are not very appropriate. The lognormal model seems t=
o provide a very nice fit; compared to a constant hazard, the hazard is sug=
gested 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 lognorm=
al survival function can be implemented in NONMEM, and/or can anyone sugges=
t 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.schoemaker_at_occams.com<mailto:rik.schoemaker_at_occams.com>

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Received on Thu Aug 29 2019 - 10:03:18 EDT

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