Re: Time to event analysis using NONMEM

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 [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