RE: unidentified cause of "F OR DERIVATIVE RETURNED BY PRED IS INFINITE (INF) OR NOT A NUMBER (NAN)"
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
Quoted reply history
-----Original Message-----
From: [email protected] [mailto:[email protected]] On
Behalf Of Leonid Gibiansky
Sent: Friday, February 02, 2018 7:13 AM
To: HUI, Ka Ho <[email protected]>; [email protected]
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
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>
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>
> 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
>
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>
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>
> .,2,4,27286.33043,4547.72,0,0,0,1,4
>
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>
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>
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>
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>
> .,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
>
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>
> .,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
>
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>
> .,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
>
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>
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>
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>
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>
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>
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>
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>
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>
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