Dear NMuser I am trying to analyze time to repeated event data using NONMEM. The response were obtained till 24 hours after drug administration. Inhibitory Emax model was implemented. I am getting unreasonable parameter estimates which is far beyond what data say. If some body can point out what i am doing wrong, it would be very helpful. Thank you in advance.
Hyewon Data set (# of observations =62, # of patients=50 ) C ID TIME CS MDV AUC . 101 0 . 1 1.111 . 101 0.05 0 0 1.111 . 101 2 0 0 1.111 . 102 0 . 1 0 . 102 24 1 0 0 . 103 0 . 1 0.999 . 103 0.75 . 0 0.999 .... Model File $PROB RUN# 101 $INPUT C ID TIME CS MDV AUC ;CS:0=having event,1=censored $DATA .data.csv IGNORE=C $SUBROUTINE ADVAN=6 TOL=6 $MODEL COMP=(HAZARD) $PK LAMD=THETA(1)*EXP(ETA(1)) ;scale factor ALPH=THETA(2) ;shape factor EC=THETA(3) ;AUC when effect is half of its max EFF=1-AUC/(EC+AUC) ;drug effect $DES DEL=1E-6 DADT(1)=LAMD*ALPH*(TIME+DEL)**(ALPH-1)*EXP(-LAMD*(TIME+DEL)**ALPH)*EFF $ERROR DEL2=1E-6 IF(NEWIND.NE.2) OLDCHZ=0 CHZ=A(1)-OLDCHZ OLDCHZ=A(1) SUR=EXP(-CHZ) HAZNOW=LAMD*ALPH*(TIME+DEL2)**(ALPH-1)*EXP(-LAMD*(TIME+DEL2)**ALPH)*EFF IF(CS.EQ.1) Y=SUR ;survival prob of censored IF(CS.EQ.0) Y=SUR*HAZNOW ;pdf of event $THETA (0,10) ;[scale factor] (0,1.0) ;[shaph factor] (0,0.01) ;[AUC at half of Emax] $OMEGA 0.01 ;[p] omega(1,1) $EST METHOD=COND LIKE LAPLACIAN PRINT=5 SIG=3 MAX=9999 MSFO=101.msf $COV PRINT=E $TABLE ID TIME SUR AUC ONEHEADER NOPRINT FILE=101.tab
