Matthew, I'm guessing this error occurs because you fix the $OMEGA BLOCK(1) for ETA_CL_OCC1 to 0. The way the model is parameterized, to get rid of the IOV, you only need to fix the OMG_CL_OCC to 0 in the $THETA block, and leave the $OMEGA BLOCK(1) for ETA_CL_OCC1 alone (fixed to 1). Agree with Leonid to reduce the IOVs to a more manageable number.
Ken -----Original Message----- From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On Behalf Of Leonid Gibiansky Sent: Friday, February 02, 2018 7:13 AM To: HUI, Ka Ho <matthew....@link.cuhk.edu.hk>; nmusers@globomaxnm.com Subject: Re: [NMusers] unidentified cause of "F OR DERIVATIVE RETURNED BY PRED IS INFINITE (INF) OR NOT A NUMBER (NAN)" I think this is overkill to have 10 occasions, and this could be a problem. Try to start first with 2 occasions (e.g, first 5 doses and the rest). If this works it means that it is just a numerical problem. Also, just to check, try Y=LOG(F+0.0001)+EPS_EXP to remove the possibility of F=0. Thanks Leonid On 2/2/2018 4:17 AM, HUI, Ka Ho wrote: > Dear nmusers, > > I have trouble figuring out the cause of the error I am encountering: > > 0INDIVIDUAL NO. 1 ID= 2.00000000000000E+00 > (WITHIN-INDIVIDUAL) DATA REC NO. 2 > > ... > > OCCURS DURING SEARCH FOR ETA AT INITIAL VALUE, ETA=0 > > F OR DERIVATIVE RETURNED BY PRED IS INFINITE (INF) OR NOT A NUMBER (NAN). > > To my own experience, this error is usually due to some mistakes in > the coding, such as the div/0 error occurring at the dosing record. > However, for this time, after I eliminated a few other possible > causes, it appears that the error will occur whenever I remove the > occasional variability from the model (by fixing variability to ZERO), > and this makes no sense to me. > > I have attached a minimal reproducible example at the bottom. Any help > is appreciated and thank you for your attention. > > Best Regards, > > Matthew > > $SIZES DIMTMP=1000 > > $PROBLEM MODEL > > $INPUT C ID DOSE_N AMT=DOSE_UM RATE=RATE_UM TIME CP_UM > DV=CP_LN_UM MDV EVID > > $DATA DATAFILE_TEST.csv IGNORE=@ > > $SUBROUTINE ADVAN3 TRANS4 > > $PK > > ;SETTING LLOQ > > IF (NEWIND.EQ.0) THEN > > LN_LLOQ=-2.9999 > > ENDIF > > ;INTEROCCASION VARIABILITY > > OCC1=0 > > IF (DOSE_N.EQ.1) OCC1=1 > > OCC2=0 > > IF (DOSE_N.EQ.2) OCC2=1 > > OCC3=0 > > IF (DOSE_N.EQ.3) OCC3=1 > > OCC4=0 > > IF (DOSE_N.EQ.4) OCC4=1 > > OCC5=0 > > IF (DOSE_N.EQ.5) OCC5=1 > > OCC6=0 > > IF (DOSE_N.EQ.6) OCC6=1 > > OCC7=0 > > IF (DOSE_N.EQ.7) OCC7=1 > > OCC8=0 > > IF (DOSE_N.EQ.8) OCC8=1 > > OCC9=0 > > IF (DOSE_N.EQ.9) OCC9=1 > > OCC10=0 > > IF (DOSE_N.EQ.10) OCC10=1 > > OCC11=0 > > IF (DOSE_N.EQ.11) OCC11=1 > > OCC12=0 > > IF (DOSE_N.EQ.12) OCC12=1 > > ;THETA DEFINITION > > TVCL=THETA(1) > > TVV1=THETA(2) > > TVQ=THETA(3) > > TVV2=THETA(4) > > OMG_CL=THETA(5) > > OMG_V1=THETA(6) > > OMG_Q=THETA(7) > > OMG_V2=THETA(8) > > SGM_EXP=THETA(9) > > OMG_CL_OCC=THETA(10) > > ;ETA DEFINITION > > ETA_CL=OMG_CL*ETA(1) > > ETA_V1=OMG_V1*ETA(2) > > ETA_Q=OMG_Q*ETA(3) > > ETA_V2=OMG_V2*ETA(4) > > > ETA_CL_OCC=OMG_CL_OCC*(OCC1*ETA(5)+OCC2*ETA(6)+OCC3*ETA(7)+OCC4*ETA(8) > +OCC5*ETA(9)+OCC6*ETA(10)+OCC7*ETA(11)+OCC8*ETA(12)+OCC9*ETA(13)+OCC10 > *ETA(14)+OCC11*ETA(15)+OCC12*ETA(16)) > > ;EFFECT DEFINITION > > ;CLEARANCE > > POP_CL=TVCL > > CL=POP_CL*EXP(ETA_CL+ETA_CL_OCC) > > ;CENTRAL VOLUME > > POP_V1=TVV1 > > V1=POP_V1*EXP(ETA_V1) > > ;INTERCOMPARTMENTAL CLEARANCE > > POP_Q=TVQ > > Q=POP_Q*EXP(ETA_Q) > > ;PERIPHERAL VOLUME > > POP_V2=TVV2 > > V2=POP_V2*EXP(ETA_V2) > > ;REQUIRED CONSTANT > > S1=V1 > > $THETA > > (0,9,1000000) ;TVCL > > (0,18,1000000) ;TVV1 > > (0,0.75,1000000) ;TVQ > > (0,7,1000000) ;TVV2 > > (0,0.3,1000000) ;OMG_CL > > (0,0.3,1000000) ;OMG_V1 > > (0,0.3,1000000) ;OMG_Q > > (0,0.3,1000000) ;OMG_V2 > > (0,0.3,1000000) ;SGM_EXP > > (0,0.3,1000000) ;OMG_CL_OCC ;Change to 0 FIX to remove occasional > variability > > $ERROR > > EPS_EXP=SGM_EXP*EPS(1) > > Y=LOG(F)+EPS_EXP > > $OMEGA BLOCK(1) 1 FIX ;ETA_CL > > $OMEGA BLOCK(1) 1 FIX ;ETA_V1 > > $OMEGA BLOCK(1) 1 FIX ;ETA_Q > > $OMEGA BLOCK(1) 1 FIX ;ETA_V2 > > $OMEGA BLOCK(1) 1 FIX ;ETA_CL_OCC1 ;Change to 0 FIX to remove > occasional variability > > $OMEGA BLOCK(1) SAME ;ETA_CL_OCC2 > > $OMEGA BLOCK(1) SAME ;ETA_CL_OCC3 > > $OMEGA BLOCK(1) SAME ;ETA_CL_OCC4 > > $OMEGA BLOCK(1) SAME ;ETA_CL_OCC5 > > $OMEGA BLOCK(1) SAME ;ETA_CL_OCC6 > > $OMEGA BLOCK(1) SAME ;ETA_CL_OCC7 > > $OMEGA BLOCK(1) SAME ;ETA_CL_OCC8 > > $OMEGA BLOCK(1) SAME ;ETA_CL_OCC9 > > $OMEGA BLOCK(1) SAME ;ETA_CL_OCC10 > > $OMEGA BLOCK(1) SAME ;ETA_CL_OCC11 > > $OMEGA BLOCK(1) SAME ;ETA_CL_OCC12 > > $SIGMA > > 1 FIX ;EPS_EXP > > $ESTIMATION MAXEVAL=9999 PRINT=1 METHOD=1 INTERACTION NUMERICAL SLOW > LAPLACIAN NOABORT > > $COVARIANCE PRINT=E > > C,ID,DOSE_N,AMT=DOSE_UM,RATE=RATE_UM,TIME,CP_UM,DV=CP_LN_UM,MDV,EVID > > .,2,1,32743.59651,5457.27,0,0,0,1,1 > > .,2,1,0,0,6,730,6.593044534,0,0 > > .,2,1,0,0,24,140,4.941642423,0,0 > > .,2,1,0,0,48,20,2.995732274,0,0 > > .,2,1,0,0,72,5.1,1.62924054,0,0 > > .,2,1,0,0,96,1.7,0.530628251,0,0 > > .,2,1,0,0,120,0.97,-0.030459207,0,0 > > .,2,1,0,0,144,0.005,-3,0,0 > > .,2,2,27286.33043,4547.72,0,0,0,1,4 > > .,2,2,0,0,6,920,6.82437367,0,0 > > .,2,2,0,0,24,46,3.828641396,0,0 > > .,2,2,0,0,48,0.93,-0.072570693,0,0 > > .,2,2,0,0,72,0.23,-1.46967597,0,0 > > c,2,2,0,0,96,14,2.63905733,0,0 > > .,2,2,0,0,120,0.06,-2.813410717,0,0 > > .,2,3,27286.33043,4547.72,0,0,0,1,4 > > .,2,3,0,0,6,910,6.8134446,0,0 > > .,2,3,0,0,24,16,2.772588722,0,0 > > .,2,3,0,0,48,0.28,-1.272965676,0,0 > > .,2,3,0,0,72,0.09,-2.407945609,0,0 > > .,2,3,0,0,96,0,0,1,2 > > .,2,4,27286.33043,4547.72,0,0,0,1,4 > > .,2,4,0,0,6,820,6.70930434,0,0 > > .,2,4,0,0,24,9.7,2.272125886,0,0 > > .,2,4,0,0,48,1.7,0.530628251,0,0 > > .,2,4,0,0,72,0.14,-1.966112856,0,0 > > .,2,4,0,0,96,0.005,-3,0,0 > > .,2,5,27286.33043,4547.72,0,0,0,1,4 > > .,2,5,0,0,6,900,6.802394763,0,0 > > .,2,5,0,0,24,30,3.401197382,0,0 > > .,2,5,0,0,48,1.9,0.641853886,0,0 > > .,2,5,0,0,72,0.32,-1.139434283,0,0 > > .,2,5,0,0,96,0.19,-1.660731207,0,0 > > .,2,5,0,0,120,0.07,-2.659260037,0,0 > > .,2,6,27286.33043,4547.72,0,0,0,1,4 > > .,2,6,0,0,6,710,6.56526497,0,0 > > .,2,6,0,0,24,6.3,1.840549633,0,0 > > .,2,6,0,0,48,0.27,-1.30933332,0,0 > > .,2,6,0,0,72,0.08,-2.525728644,0,0 > > .,3,1,48235.19056,8039.2,0,0,0,1,1 > > .,3,1,0,0,6,750,6.620073207,0,0 > > .,3,1,0,0,24,29.5,3.384390263,0,0 > > .,3,1,0,0,48,3.5,1.252762968,0,0 > > .,3,1,0,0,72,0.77,-0.261364764,0,0 > > .,3,1,0,0,96,0.47,-0.755022584,0,0 > > .,3,1,0,0,120,0.005,-3,0,0 > > .,3,2,30146.9941,5024.5,0,0,0,1,4 > > .,3,2,0,0,24,30,3.401197382,0,0 > > .,3,2,0,0,48,1.7,0.530628251,0,0 > > .,3,2,0,0,72,0.71,-0.342490309,0,0 > > .,3,2,0,0,96,0.35,-1.049822124,0,0 > > .,3,2,0,0,120,0.29,-1.237874356,0,0 > > .,3,2,0,0,144,0.005,-3,0,0 > > .,3,3,24117.59528,4019.6,0,0,0,1,4 > > .,3,3,0,0,6,660,6.492239835,0,0 > > .,3,3,0,0,24,18.5,2.917770732,0,0 > > .,3,3,0,0,48,0.95,-0.051293294,0,0 > > .,3,3,0,0,72,0.41,-0.891598119,0,0 > > .,3,3,0,0,96,0.19,-1.660731207,0,0 > > .,3,3,0,0,120,0.13,-2.040220829,0,0 > > .,3,3,0,0,144,0.005,-3,0,0 > > .,3,4,24117.59528,4019.6,0,0,0,1,4 > > .,3,4,0,0,6,620,6.429719478,0,0 > > .,3,4,0,0,24,8.3,2.116255515,0,0 > > .,3,4,0,0,48,1.7,0.530628251,0,0 > > .,3,4,0,0,72,0.17,-1.771956842,0,0 > > .,3,4,0,0,96,0.09,-2.407945609,0,0 > > .,3,5,27132.29469,4522.05,0,0,0,1,4 > > .,3,5,0,0,6,870,6.768493212,0,0 > > .,3,5,0,0,24,22.5,3.113515309,0,0 > > .,3,5,0,0,48,0.94,-0.061875404,0,0 > > .,3,5,0,0,72,0.43,-0.84397007,0,0 > > .,3,5,0,0,96,0.21,-1.560647748,0,0 > > .,3,5,0,0,120,0.14,-1.966112856,0,0 > > .,3,5,0,0,144,0.005,-3,0,0 > > .,3,6,27132.29469,4522.05,0,0,0,1,4 > > .,3,6,0,0,6,660,6.492239835,0,0 > > .,3,6,0,0,24,7.2,1.974081026,0,0 > > .,3,6,0,0,48,0.6,-0.510825624,0,0 > > .,3,6,0,0,72,0.21,-1.560647748,0,0 > > .,3,6,0,0,96,0.1,-2.302585093,0,0 > > .,3,6,0,0,120,0.005,-3,0,0 > > .,3,7,27132.29469,4522.05,0,0,0,1,4 > > .,3,7,0,0,6,720,6.579251212,0,0 > > .,3,7,0,0,24,14.4,2.667228207,0,0 > > .,3,7,0,0,48,0.51,-0.673344553,0,0 > > .,3,7,0,0,72,0.17,-1.771956842,0,0 > > .,3,7,0,0,96,0.09,-2.407945609,0,0 > > .,3,8,27132.29469,4522.05,0,0,0,1,4 > > .,3,8,0,0,6,830,6.721425701,0,0 > > .,3,8,0,0,24,12.5,2.525728644,0,0 > > .,3,8,0,0,48,0.85,-0.162518929,0,0 > > .,3,8,0,0,72,0.44,-0.820980552,0,0 > > .,3,8,0,0,96,0.29,-1.237874356,0,0 > > .,3,8,0,0,120,0.2,-1.609437912,0,0 > > .,3,8,0,0,144,0.005,-3,0,0 > > .,3,9,27132.29469,4522.05,0,0,0,1,4 > > .,3,9,0,0,6,670,6.507277712,0,0 > > .,3,9,0,0,24,8.5,2.140066163,0,0 > > .,3,9,0,0,48,0.77,-0.261364764,0,0 > > .,3,9,0,0,72,0.34,-1.078809661,0,0 > > .,3,9,0,0,96,0.18,-1.714798428,0,0 > > .,3,9,0,0,120,0.05,-2.995732274,0,0 > > .,3,10,27132.29469,4522.05,0,0,0,1,4 > > .,3,10,0,0,6,1080,6.98471632,0,0 > > .,3,10,0,0,24,56,4.025351691,0,0 > > .,3,10,0,0,48,5.1,1.62924054,0,0 > > .,3,10,0,0,72,1.5,0.405465108,0,0 > > .,3,10,0,0,96,0.64,-0.446287103,0,0 > > .,3,10,0,0,120,0.54,-0.616186139,0,0 > > .,3,10,0,0,144,0.31,-1.171182982,0,0 > > .,3,10,0,0,168,0.23,-1.46967597,0,0 > > .,3,10,0,0,192,0.12,-2.120263536,0,0 > > .,3,10,0,0,216,0.06,-2.813410717,0,0 > > .,3,11,24117.59528,4019.6,0,0,0,1,4 > > .,3,11,0,0,6,870,6.768493212,0,0 > > .,3,11,0,0,24,19.2,2.954910279,0,0 > > .,3,11,0,0,48,0.87,-0.139262067,0,0 > > .,3,11,0,0,72,0.4,-0.916290732,0,0 > > .,3,11,0,0,96,0.2,-1.609437912,0,0 > > .,3,11,0,0,120,0.12,-2.120263536,0,0 > > .,3,11,0,0,144,0.005,-3,0,0 > This e-mail, including any attachments, is meant only for the intended recipient of the transmission, and may be a confidential or privileged communication. 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