Unexpected differences in predictions between NM 6.2.0 and NM 7.1.2

Dear R-users, I have recently observed a very puzzling difference of behavior between NM 6.2.0 and NM 7.1.2, while trying to reproduce the simulation examples described in Martin Bergstrand's paper 'Handling data below the limit of quantification in mixed effect models' (AAPS Journal 2009, 11-2). My model corresponds to Martins' model B (2-cmt linear model with single IV dosing) and implement my interpretation of the residual variability described in his equation 3 (see code below). When I run the code in NONMEM 7.1.2,, all the PRED values are reported as NaN and RES values either as NaN or 0. NM6 returns non-NaN values for PRED and RES, but there does not seem to be any differences in simulated DV. Did anybody experienced the same differences? In my case, could they be explained by an improper implementation of the RV model? As a side note, I would also be interested to know if a reference in the literature would describe the properties of this particular RUV model. Thank you Sebastien Bihorel -------- $PROBLEM base-2cmt-sim $DATA basedata.csv IGNORE=@ $INPUT ID TIME AMT RATE CMT EVID DV MDV STDY $THETA (0.,5.) ;1- clearance (0.,20.) ;2- central compartment volume (0.,5.) ;3- distribution clearance (0.,100.) ;4- peripheral compartment volume (0.,0.1) ;5- 'additive' log RV (0.,0.1) ;6- 'second' log RV term $OMEGA 0.3 ;1- IIV in clearance 0.3 ;2- IIV in central compartment volume 0.3 ;3- IIV in distribution clearance 0.3 ;4- IIV in peripheral compartment volume $SIGMA 1 FIX ;1- 'additive' log RV 1 FIX ;2- 'second' log RV term $SUBROUTINES ADVAN3 TRANS4 $PK ; Model parameter assignment TVCL=THETA(1) TVV1=THETA(2) TVQ =THETA(3) TVV2=THETA(4) ECL=EXP(ETA(1)) EV1=EXP(ETA(2)) EQ =EXP(ETA(3)) EV2=EXP(ETA(4)) ; PREDPP required variables F1=1.0 ; bioavailability in central compartment CL=TVCL*ECL ; elimination clearance V1=TVV1*EV1 ; volume of the central compartment Q =TVQ*EQ ; inter-compartment distribution clearance V2=TVV2*EV2 ; volume of the peripheral compartment S1=V1 $ERROR ;set up Dose flag DFLG=0 IF(AMT.GT.0)DFLG=1 IPRED=LOG(F+DFLG) W1=THETA(5)*EPS(1) W2=THETA(6)*EPS(2) W=SQRT(W1*W1+(W2*(1-F/(0.5+F)))**2) Y=IPRED+W $SIM (123456) ONLYSIM $TABLE ID TIME AMT RATE CMT EVID DV MDV STDY W NOPRINT ONEHEADER FILE=base-2cmt-sim.tbl basedata.csv Description: MS-Excel spreadsheet