NONMEM Users Network Archive

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Re: Time to event analysis using NONMEM

From: Nick Holford <n.holford>
Date: Tue, 09 Jun 2009 18:25:52 +0200

Anubha,

You need to have a zero time record for each observation. NONMEM needs
to integrate the hazard from time 0 upto the time of the event.

You should also have CS=DV and use MDV=1 for the TIME zero record and
MDV=0 for the event observation.

The event 'observation' is either 1 (censored) or 0 (actual event).
While there is nothing wrong with the way you describe the events it is
exactly the reverse of the traditional way used in survival analysis
which uses 0 for a censored event and 1 for an actual event.

Note that with single event data the model will run more quickly with
METHOD=ZERO (i.e. FO). There is no need to waste computation time using
METHOD=COND and LAPLACIAN.

Best wishes,

Nick

Anubha_Gupta
>
> Dear NMUsers
>
> I am trying to analyse time to single event data using NONMEM VI. I am
> getting the following termination message. If some body could point
> out what I am doing wrong or may be elaborate on the error message
> that would be very helpful.
>
> Thanks in advance
>
> Anubha
>
>
> 0PROGRAM TERMINATED BY OBJ
> ERROR IN CLIK WITH INDIVIDUAL 1 ID=0.40000000E+01
> CONDITIONAL LIKELIHOOD FOR DATA FROM OBS RECORD 1
> ESTIMATED TO BE NEGLIGIBLE
> MESSAGE ISSUED FROM ESTIMATION STEP
> AT INITIAL OBJ. FUNCTION EVALUATION
>
>
> Data set
>
>
> C STUD ID TIME CS DOSE
> . 101
> 4
>
> 111
>
> 0
>
> 0.4
> . 101
> 5
>
> 51
>
> 0
>
> 0.4
> . 101
> 6
>
> 31
>
> 0
>
> 0.8
> C Missing DV 101
> 7
> . .
> 0.8
> . 101
> 8
>
> 59
>
> 0
>
> 1.6
> . 101
> 9
>
> 477
>
> 1
>
> 3.2
> . 101
> 11
>
> 278
>
> 0
>
> 3.2
> . 101
> 12
>
> 58
>
> 0
>
> 6.4
>
> CS=1 is the censored event
> TIME is in days
>
>
> Model file:
>
> $PROB Time To Event data
>
> $INPUT C STUD ID TIME=DV CS DOSE
>
> $DATA
>
> IGNORE=C
>
> $SUBR ADVAN=6 TOL=6
> $MODEL COMP=(RISK)
>
> $PK
>
> BASE = THETA(1)*EXP(ETA(1)) ;the ETA is a placeholder here
>
> $DES
> DADT(1)=BASE ;hazard
>
> $ERROR
>
>
> HZ = A(1) ;hazard
> SUR = EXP(-HZ) ;survival probability
> DENS=HZ*SUR
> Y = (1-CS)*DENS + CS*SUR
>
> $THETA (0,.025) ; BASE
> $OMEGA 0 FIX
>
> $ESTIM MAXEVAL=9990 METHOD = COND LAPLACE LIKE PRINT=1 MSFO=msfb01
> $COV PRINT=E
>
>
>
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--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
n.holford
mobile: +33 64 271-6369 (Apr 6-Jul 17 2009)
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

Received on Tue Jun 09 2009 - 12:25:52 EDT

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