Re: Time to event analysis using NONMEM

From: Nick Holford <[email protected]> To: nmusers <[email protected]> Date: 09/06/2009 19:17 Subject: Re: [NMusers] Time to event analysis using NONMEM Sent by: [email protected] Leonid, Your suggestion to use $PRED is fine for this simple example with a constant hazard (or easily integrable function). But more generally the hazard may be tough to integrate analytically and thus one must use $PK and and $DES. Serge, This is an interesting suggestion. Can you be more explicit about when truncation to zero might be a problem which would be ameliorated by using -2LL? Nick Leonid Gibiansky wrote: > Anubha > You do not have time=0 records, therefore, A(1)=0 > Try > HZ=BASE*TIME > (and use $PRED rather than $PK) > > Leonid Serge Guzy wrote: > I am not sure it will help but for time to event data I always used > the log-likelihood instead of the likelihood. This is usually done to > prevent truncation to zero (Like the default when using the normal > likelihood). Did you try? > > [email protected] wrote: >> 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 >> >> >> >> THIS EMAIL AND ANY ATTACHED FILES ARE CONFIDENTIAL. >> If you are not the intended recipient you are notified that any >> disclosure, reproduction,copying, distribution, or action taken in >> reliance on the contents of this information is strictly prohibited. >> If you have received this transmission in error please notify the >> sender immediately and then delete this email. Email transmission >> cannot be guaranteed to be secure or error free as information could >> be intercepted, corrupted, lost, destroyed,arrive late or incomplete, >> or contain viruses. The company/sender accepts no liability for any >> changes made to this email during transmission or any damage caused >> by any virus transmitted by this email. Any views or opinions >> expressed in this email are solely those of the author and do not >> necessarily represent those of the company. The company/sender >> accepts no liability for the content of this email, or for the >> consequences of any actions taken on the basis of the information >> provided, unless that information is subsequently confirmed in writing. >> -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand [email protected] tel:+64(9)923-6730 fax:+64(9)373-7090 mobile: +33 64 271-6369 (Apr 6-Jul 17 2009) http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford ______________________________________________________________________ This email has been scanned by the MessageLabs Email Security System. For more information please visit http://www.messagelabs.com/email ______________________________________________________________________ THIS EMAIL AND ANY ATTACHED FILES ARE CONFIDENTIAL. If you are not the intended recipient you are notified that any disclosure, reproduction,copying, distribution, or action taken in reliance on the contents of this information is strictly prohibited. If you have received this transmission in error please notify the sender immediately and then delete this email. Email transmission cannot be guaranteed to be secure or error free as information could be intercepted, corrupted, lost, destroyed,arrive late or incomplete, or contain viruses. The company/sender accepts no liability for any changes made to this email during transmission or any damage caused by any virus transmitted by this email. Any views or opinions expressed in this email are solely those of the author and do not necessarily represent those of the company. The company/sender accepts no liability for the content of this email, or for the consequences of any actions taken on the basis of the information provided, unless that information is subsequently confirmed in writing. <<inline: graycol.gif>> <<inline: ecblank.gif>>