Use of NONMEM With The Standard Two-Stage Estimation Method

NONMEM may be used to quickly and conveniently obtain the first-stage PK estimates with the standard two stage estima- tion method. Using (for the sake of illustration) a simple one-compartment model with constant cv residual error, the control stream should include the following: $SUBROUTINE ADVAN1 TRANS2 $PK CL=THETA(1)*EXP(ETA(1)) V =THETA(2)*EXP(ETA(2)) $ERROR Y=F+F*EXP(ETA(3))*ERR(1) $THETA 5 50 ;these are rough typical population values $OMEGA 100 100 100 $SIGMA 1 FIXED $ESTIMATION MAXEVAL=0 POSTHOC FOCE INTERACTION $TABLE CL V FILE=firststage MAXEVALS=0 means that no population estimation will occur POSTHOC means that individual conditional estimates of CL and V will be obtained. The Bayesian influence is nill, since OMEGA is purposely chosen to be very large. What results then, are simple extended least squares estimates. FOCE needed only because without it, INTERACTION cannot also be used. INTERACTION means that individual estimates of ETA(3) are also obtained. EXP(ETA(3)) is in effect, the standard deviation of ERR(1) since SIGMA is fixed to 1. Were SIGMA not fixed to 1, and were EXP(ETA(3)) absent, then all residual errors, for all individuals, would have the same cv. The way it is, the cv varies between individuals, as "with the STS method". CL and V the first-stage (ELS) estimates