Time to event analysis using NONMEM

From: [email protected] [mailto:[email protected]] On Behalf Of [email protected] Sent: Tuesday, June 09, 2009 5:24 PM To: [email protected] Subject: [NMusers] Time to event analysis using NONMEM 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.

________________________________ From: [email protected] [mailto:[email protected]] On Behalf Of [email protected] Sent: Tuesday, June 09, 2009 8:24 AM To: [email protected] Subject: [NMusers] Time to event analysis using NONMEM 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. -- The information contained in this email message may contain confidential or legally privileged information and is intended solely for the use of the named recipient(s). No confidentiality or privilege is waived or lost by any transmission error. If the reader of this message is not the intended recipient, please immediately delete the e-mail and all copies of it from your system, destroy any hard copies of it and notify the sender either by telephone or return e-mail. Any direct or indirect use, disclosure, distribution, printing, or copying of any part of this message is prohibited. Any views expressed in this message are those of the individual sender, except where the message states otherwise and the sender is authorized to state them to be the views of XOMA.

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. 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