RE: [NMusers] ERROR NUMBER OF BASIC PK PARAMETERS EXCEEDS VALUE OF NPARAM IN $MODEL
Thank you, Alison! Paul Hutson, PharmD, BCOP Professor UWisc School of Pharmacy T: 608.263.2496 F: 608.265.5421 -Original Message- From: Alison Boeckmann Sent: Wednesday, July 31, 2019 1:04 PM To: Paul Hutson ; Leonid Gibiansky ; 'nmusers' ; ajbf Subject: Re: [NMusers] ERROR NUMBER OF BASIC PK PARAMETERS EXCEEDS VALUE OF NPARAM IN $MODEL (1) I agree with Leonid: don't code NPARAM. NPARAM is required when the user writes a Fortran DES routine, e.g., $SUBR DES=mydes When $DES abbreviated code is present, NMTRAN will count the basic PK parameters and set NPARAM in the generated MODEL routine. For example, if you omit NPARAM from the $MODEL record, the generated MODEL routine sets NPAR=007 This is reported in the PREDPP portion of the NONMEM output: MAXIMUM NO. OF BASIC PK PARAMETERS: 7 If both $DES and NPARAM are present, NPARAM must be at least as large as the number counted by NMTRAN, but may not be smaller. (NMTRAN uses the larger value in the MODEL routine.) (2) You ask: "It appears that NONMEM wants additional parameters added to NPARAM when I added calculated value CC in the $DES block. " The code in $PK is MIC=0.12 ; SEEKING TIME AND AUC ABOVE 0.12 MCG/ML The code in $DES is CC=A(1)/V1 IF(CC.GT.MIC) RT=1 It is MIC that looks to NMTRAN like a basic PK parameter. You can see the following code in subroutine PK in FSUBS: P02=MIC GG(0002,1,1)=P02 (3) You ask: "What is also odd to me is that the fault is called on the line defining DADT(2)." I'll pass on this one. Sometimes NMTRAN may report an error on a line near where the error is detected, not the exact line. It may be easy to fix for this example and yet the fix may break some other control stream. -- Alison On Wed, Jul 31, 2019, at 5:56 AM, Paul Hutson wrote: > Hello, Leonid, and thank you for the correction on the IWRES and the > suggestion on the IRES. > Regarding NPARAM, you are correct, the model runs if the NPARM count is > removed from the $MODEL statement. It was curious to me that if it > was included that it was counting the calculated value CC in the $DES > block as a parameter. > Take care. > Paul > > Paul Hutson, PharmD, BCOP > Professor > UWisc School of Pharmacy > T: 608.263.2496 > F: 608.265.5421 > > -Original Message- > From: Leonid Gibiansky > Sent: Tuesday, July 30, 2019 11:53 PM > To: Paul Hutson ; 'nmusers' > > Subject: Re: [NMusers] ERROR NUMBER OF BASIC PK PARAMETERS EXCEEDS > VALUE OF NPARAM IN $MODEL > > Not sure why would we need NPARAM there, is it necessary? I think one > can skip it. > > On the different topic, expression for IWRES is not correct: > > IWRES=IRES/(IPRED * EPS(1) + EPS(2)) > > This is the version that should be used: > > IWRES=IRES/SQRT(IPRED**2 * SIGMA(1,1) + SIGMA(2,2)) > > Also it is more traditional to define IRES=DV-IPRED (negative residual > corresponds to over-predictions; observed=predicted + residual error). > > Regards > Leonid > > > On 7/29/2019 2:49 PM, Paul Hutson wrote: > > I've fixed it by increasing NPARAM until it worked (increasing to > > 7), but can anyone explain why I get this message for a 3 > > compartment model with additional compartments to output a time > > above a concentration threshold (#4) and AUC while above that concentration > > threshold (#5)? > > It appears that NONMEM wants additional parameters added to NPARAM > > when I added calculated value CC in the $DES block. What is also > > odd to me is that the fault is called on the line defining DADT(2). > > Thanks in advance. Paul > > > > $SUBROUTINES ADVAN6 TOL=3 > > > > $MODEL NCOMP=5 NPARAM=6 > > > > COMP=(CENTRAL DEFDOSE DEFOBS) > > > > COMP=(TISU1) > > > > COMP=(TISU2) > > > > COMP=(TTIME) > > > > COMP=(AUCC) > > > > ;--PK BLOCK > > > > $PK > > > > MIC=0.12 ; SEEKING TIME AND AUC ABOVE 0.12 MCG/ML > > > > TVCL = POP_CL > > > > TVV1=POP_V1 > > > > TVQ2=POP_Q2 > > > > TVV2=POP_V2 > > > > TVQ3=POP_Q3 > > > > TVV3=POP_V3 > > > > CL=TVCL * EXP(ETA(1)) > > > > V1=TVV1 * EXP(ETA(2)) > > > > Q2=TVQ2 * EXP(ETA(3)) > > > > V2=TVV2 * EXP(ETA(4)) > > > > Q3=TVQ3 * EXP(ETA(5)) > > > > V3=TVV3 * EXP(ETA(6)) > > > > K10=CL/V1 > > > > K12=Q2/V1 > > > > K21=Q2/V2 > > > > K13=Q3/V1 > > > > K31=Q3/V3 > > > > ;DES BLOCK > > > > $DES > > > > CC=A(1)/V1 > > > > RT=0 > > > > IF(CC.GT.MIC) RT=1 > > > > DADT(1) = - A(1) * (K10 + K12 + K13) + A(2) * K21 + A(3)*K31 > > > > DADT(2) = A(1) * K12 - A(2) * K21 > > > > DADT(3) = A(1) * K13 - A(3) * K31 > > > > DADT(4)=RT ; TIME ABOVE THRESHOLD TAT > > > > DADT(5)=RT*CC ; AUC ABOVE THRESHOLD AUCAT > > > > ;- ERROR MODEL -- > > > > $ERROR > > > > IPRED = F > > > > IRES=IPRED-DV > > > > Y=IPRED * (1 + EPS(1)) + EPS(2) > > > > IWRES=IRES/(IPRED * EPS(1) + EPS(2)) > > > > TAT=A(4) > > > > AUCAT=A(5) > > > > TIS2 = A(2)/V2 > > > > TIS3 = A(3)/V3 > > > > Paul Hutson,
Re: [NMusers] ERROR NUMBER OF BASIC PK PARAMETERS EXCEEDS VALUE OF NPARAM IN $MODEL
(1) I agree with Leonid: don't code NPARAM. NPARAM is required when the user writes a Fortran DES routine, e.g., $SUBR DES=mydes When $DES abbreviated code is present, NMTRAN will count the basic PK parameters and set NPARAM in the generated MODEL routine. For example, if you omit NPARAM from the $MODEL record, the generated MODEL routine sets NPAR=007 This is reported in the PREDPP portion of the NONMEM output: MAXIMUM NO. OF BASIC PK PARAMETERS: 7 If both $DES and NPARAM are present, NPARAM must be at least as large as the number counted by NMTRAN, but may not be smaller. (NMTRAN uses the larger value in the MODEL routine.) (2) You ask: "It appears that NONMEM wants additional parameters added to NPARAM when I added calculated value CC in the $DES block. " The code in $PK is MIC=0.12 ; SEEKING TIME AND AUC ABOVE 0.12 MCG/ML The code in $DES is CC=A(1)/V1 IF(CC.GT.MIC) RT=1 It is MIC that looks to NMTRAN like a basic PK parameter. You can see the following code in subroutine PK in FSUBS: P02=MIC GG(0002,1,1)=P02 (3) You ask: "What is also odd to me is that the fault is called on the line defining DADT(2)." I'll pass on this one. Sometimes NMTRAN may report an error on a line near where the error is detected, not the exact line. It may be easy to fix for this example and yet the fix may break some other control stream. -- Alison On Wed, Jul 31, 2019, at 5:56 AM, Paul Hutson wrote: > Hello, Leonid, and thank you for the correction on the IWRES and the > suggestion on the IRES. > Regarding NPARAM, you are correct, the model runs if the NPARM count is > removed from the $MODEL statement. It was curious to me that if it > was included that it was counting the calculated value CC in the $DES > block as a parameter. > Take care. > Paul > > Paul Hutson, PharmD, BCOP > Professor > UWisc School of Pharmacy > T: 608.263.2496 > F: 608.265.5421 > > -Original Message- > From: Leonid Gibiansky > Sent: Tuesday, July 30, 2019 11:53 PM > To: Paul Hutson ; 'nmusers' > > Subject: Re: [NMusers] ERROR NUMBER OF BASIC PK PARAMETERS EXCEEDS > VALUE OF NPARAM IN $MODEL > > Not sure why would we need NPARAM there, is it necessary? I think one > can skip it. > > On the different topic, expression for IWRES is not correct: > > IWRES=IRES/(IPRED * EPS(1) + EPS(2)) > > This is the version that should be used: > > IWRES=IRES/SQRT(IPRED**2 * SIGMA(1,1) + SIGMA(2,2)) > > Also it is more traditional to define IRES=DV-IPRED (negative residual > corresponds to over-predictions; observed=predicted + residual error). > > Regards > Leonid > > > On 7/29/2019 2:49 PM, Paul Hutson wrote: > > I've fixed it by increasing NPARAM until it worked (increasing to 7), > > but can anyone explain why I get this message for a 3 compartment > > model with additional compartments to output a time above a > > concentration threshold (#4) and AUC while above that concentration > > threshold (#5)? > > It appears that NONMEM wants additional parameters added to NPARAM > > when I added calculated value CC in the $DES block. What is also odd > > to me is that the fault is called on the line defining DADT(2). Thanks > > in advance. Paul > > > > $SUBROUTINES ADVAN6 TOL=3 > > > > $MODEL NCOMP=5 NPARAM=6 > > > > COMP=(CENTRAL DEFDOSE DEFOBS) > > > > COMP=(TISU1) > > > > COMP=(TISU2) > > > > COMP=(TTIME) > > > > COMP=(AUCC) > > > > ;--PK BLOCK > > > > $PK > > > > MIC=0.12 ; SEEKING TIME AND AUC ABOVE 0.12 MCG/ML > > > > TVCL = POP_CL > > > > TVV1=POP_V1 > > > > TVQ2=POP_Q2 > > > > TVV2=POP_V2 > > > > TVQ3=POP_Q3 > > > > TVV3=POP_V3 > > > > CL=TVCL * EXP(ETA(1)) > > > > V1=TVV1 * EXP(ETA(2)) > > > > Q2=TVQ2 * EXP(ETA(3)) > > > > V2=TVV2 * EXP(ETA(4)) > > > > Q3=TVQ3 * EXP(ETA(5)) > > > > V3=TVV3 * EXP(ETA(6)) > > > > K10=CL/V1 > > > > K12=Q2/V1 > > > > K21=Q2/V2 > > > > K13=Q3/V1 > > > > K31=Q3/V3 > > > > ;DES BLOCK > > > > $DES > > > > CC=A(1)/V1 > > > > RT=0 > > > > IF(CC.GT.MIC) RT=1 > > > > DADT(1) = - A(1) * (K10 + K12 + K13) + A(2) * K21 + A(3)*K31 > > > > DADT(2) = A(1) * K12 - A(2) * K21 > > > > DADT(3) = A(1) * K13 - A(3) * K31 > > > > DADT(4)=RT ; TIME ABOVE THRESHOLD TAT > > > > DADT(5)=RT*CC ; AUC ABOVE THRESHOLD AUCAT > > > > ;- ERROR MODEL -- > > > > $ERROR > > > > IPRED = F > > > > IRES=IPRED-DV > > > > Y=IPRED * (1 + EPS(1)) + EPS(2) > > > > IWRES=IRES/(IPRED * EPS(1) + EPS(2)) > > > > TAT=A(4) > > > > AUCAT=A(5) > > > > TIS2 = A(2)/V2 > > > > TIS3 = A(3)/V3 > > > > Paul Hutson, PharmD, BCOP > > > > Professor > > > > UWisc School of Pharmacy > > > > T: 608.263.2496 > > > > F: 608.265.5421 > > > > -- Alison Boeckmann alisonboeckm...@fastmail.fm
RE: [NMusers] ERROR NUMBER OF BASIC PK PARAMETERS EXCEEDS VALUE OF NPARAM IN $MODEL
Hello, Leonid, and thank you for the correction on the IWRES and the suggestion on the IRES. Regarding NPARAM, you are correct, the model runs if the NPARM count is removed from the $MODEL statement. It was curious to me that if it was included that it was counting the calculated value CC in the $DES block as a parameter. Take care. Paul Paul Hutson, PharmD, BCOP Professor UWisc School of Pharmacy T: 608.263.2496 F: 608.265.5421 -Original Message- From: Leonid Gibiansky Sent: Tuesday, July 30, 2019 11:53 PM To: Paul Hutson ; 'nmusers' Subject: Re: [NMusers] ERROR NUMBER OF BASIC PK PARAMETERS EXCEEDS VALUE OF NPARAM IN $MODEL Not sure why would we need NPARAM there, is it necessary? I think one can skip it. On the different topic, expression for IWRES is not correct: IWRES=IRES/(IPRED * EPS(1) + EPS(2)) This is the version that should be used: IWRES=IRES/SQRT(IPRED**2 * SIGMA(1,1) + SIGMA(2,2)) Also it is more traditional to define IRES=DV-IPRED (negative residual corresponds to over-predictions; observed=predicted + residual error). Regards Leonid On 7/29/2019 2:49 PM, Paul Hutson wrote: > I've fixed it by increasing NPARAM until it worked (increasing to 7), > but can anyone explain why I get this message for a 3 compartment > model with additional compartments to output a time above a > concentration threshold (#4) and AUC while above that concentration threshold > (#5)? > It appears that NONMEM wants additional parameters added to NPARAM > when I added calculated value CC in the $DES block. What is also odd > to me is that the fault is called on the line defining DADT(2). Thanks > in advance. Paul > > $SUBROUTINES ADVAN6 TOL=3 > > $MODEL NCOMP=5 NPARAM=6 > > COMP=(CENTRAL DEFDOSE DEFOBS) > > COMP=(TISU1) > > COMP=(TISU2) > > COMP=(TTIME) > > COMP=(AUCC) > > ;--PK BLOCK > > $PK > > MIC=0.12 ; SEEKING TIME AND AUC ABOVE 0.12 MCG/ML > > TVCL = POP_CL > > TVV1=POP_V1 > > TVQ2=POP_Q2 > > TVV2=POP_V2 > > TVQ3=POP_Q3 > > TVV3=POP_V3 > > CL=TVCL * EXP(ETA(1)) > > V1=TVV1 * EXP(ETA(2)) > > Q2=TVQ2 * EXP(ETA(3)) > > V2=TVV2 * EXP(ETA(4)) > > Q3=TVQ3 * EXP(ETA(5)) > > V3=TVV3 * EXP(ETA(6)) > > K10=CL/V1 > > K12=Q2/V1 > > K21=Q2/V2 > > K13=Q3/V1 > > K31=Q3/V3 > > ;DES BLOCK > > $DES > > CC=A(1)/V1 > > RT=0 > > IF(CC.GT.MIC) RT=1 > > DADT(1) = - A(1) * (K10 + K12 + K13) + A(2) * K21 + A(3)*K31 > > DADT(2) = A(1) * K12 - A(2) * K21 > > DADT(3) = A(1) * K13 - A(3) * K31 > > DADT(4)=RT ; TIME ABOVE THRESHOLD TAT > > DADT(5)=RT*CC ; AUC ABOVE THRESHOLD AUCAT > > ;- ERROR MODEL -- > > $ERROR > > IPRED = F > > IRES=IPRED-DV > > Y=IPRED * (1 + EPS(1)) + EPS(2) > > IWRES=IRES/(IPRED * EPS(1) + EPS(2)) > > TAT=A(4) > > AUCAT=A(5) > > TIS2 = A(2)/V2 > > TIS3 = A(3)/V3 > > Paul Hutson, PharmD, BCOP > > Professor > > UWisc School of Pharmacy > > T: 608.263.2496 > > F: 608.265.5421 >
Re: [NMusers] ERROR NUMBER OF BASIC PK PARAMETERS EXCEEDS VALUE OF NPARAM IN $MODEL
Not sure why would we need NPARAM there, is it necessary? I think one can skip it. On the different topic, expression for IWRES is not correct: IWRES=IRES/(IPRED * EPS(1) + EPS(2)) This is the version that should be used: IWRES=IRES/SQRT(IPRED**2 * SIGMA(1,1) + SIGMA(2,2)) Also it is more traditional to define IRES=DV-IPRED (negative residual corresponds to over-predictions; observed=predicted + residual error). Regards Leonid On 7/29/2019 2:49 PM, Paul Hutson wrote: I’ve fixed it by increasing NPARAM until it worked (increasing to 7), but can anyone explain why I get this message for a 3 compartment model with additional compartments to output a time above a concentration threshold (#4) and AUC while above that concentration threshold (#5)? It appears that NONMEM wants additional parameters added to NPARAM when I added calculated value CC in the $DES block. What is also odd to me is that the fault is called on the line defining DADT(2). Thanks in advance. Paul $SUBROUTINES ADVAN6 TOL=3 $MODEL NCOMP=5 NPARAM=6 COMP=(CENTRAL DEFDOSE DEFOBS) COMP=(TISU1) COMP=(TISU2) COMP=(TTIME) COMP=(AUCC) ;--PK BLOCK $PK MIC=0.12 ; SEEKING TIME AND AUC ABOVE 0.12 MCG/ML TVCL = POP_CL TVV1=POP_V1 TVQ2=POP_Q2 TVV2=POP_V2 TVQ3=POP_Q3 TVV3=POP_V3 CL=TVCL * EXP(ETA(1)) V1=TVV1 * EXP(ETA(2)) Q2=TVQ2 * EXP(ETA(3)) V2=TVV2 * EXP(ETA(4)) Q3=TVQ3 * EXP(ETA(5)) V3=TVV3 * EXP(ETA(6)) K10=CL/V1 K12=Q2/V1 K21=Q2/V2 K13=Q3/V1 K31=Q3/V3 ;DES BLOCK $DES CC=A(1)/V1 RT=0 IF(CC.GT.MIC) RT=1 DADT(1) = - A(1) * (K10 + K12 + K13) + A(2) * K21 + A(3)*K31 DADT(2) = A(1) * K12 - A(2) * K21 DADT(3) = A(1) * K13 - A(3) * K31 DADT(4)=RT ; TIME ABOVE THRESHOLD TAT DADT(5)=RT*CC ; AUC ABOVE THRESHOLD AUCAT ;- ERROR MODEL -- $ERROR IPRED = F IRES=IPRED-DV Y=IPRED * (1 + EPS(1)) + EPS(2) IWRES=IRES/(IPRED * EPS(1) + EPS(2)) TAT=A(4) AUCAT=A(5) TIS2 = A(2)/V2 TIS3 = A(3)/V3 Paul Hutson, PharmD, BCOP Professor UWisc School of Pharmacy T: 608.263.2496 F: 608.265.5421
[NMusers] ERROR NUMBER OF BASIC PK PARAMETERS EXCEEDS VALUE OF NPARAM IN $MODEL
I've fixed it by increasing NPARAM until it worked (increasing to 7), but can anyone explain why I get this message for a 3 compartment model with additional compartments to output a time above a concentration threshold (#4) and AUC while above that concentration threshold (#5)? It appears that NONMEM wants additional parameters added to NPARAM when I added calculated value CC in the $DES block. What is also odd to me is that the fault is called on the line defining DADT(2). Thanks in advance. Paul $SUBROUTINES ADVAN6 TOL=3 $MODEL NCOMP=5 NPARAM=6 COMP=(CENTRAL DEFDOSE DEFOBS) COMP=(TISU1) COMP=(TISU2) COMP=(TTIME) COMP=(AUCC) ;--PK BLOCK $PK MIC=0.12 ; SEEKING TIME AND AUC ABOVE 0.12 MCG/ML TVCL = POP_CL TVV1=POP_V1 TVQ2=POP_Q2 TVV2=POP_V2 TVQ3=POP_Q3 TVV3=POP_V3 CL=TVCL * EXP(ETA(1)) V1=TVV1 * EXP(ETA(2)) Q2=TVQ2 * EXP(ETA(3)) V2=TVV2 * EXP(ETA(4)) Q3=TVQ3 * EXP(ETA(5)) V3=TVV3 * EXP(ETA(6)) K10=CL/V1 K12=Q2/V1 K21=Q2/V2 K13=Q3/V1 K31=Q3/V3 ;DES BLOCK $DES CC=A(1)/V1 RT=0 IF(CC.GT.MIC) RT=1 DADT(1) = - A(1) * (K10 + K12 + K13) + A(2) * K21 + A(3)*K31 DADT(2) = A(1) * K12 - A(2) * K21 DADT(3) = A(1) * K13 - A(3) * K31 DADT(4)=RT ; TIME ABOVE THRESHOLD TAT DADT(5)=RT*CC ; AUC ABOVE THRESHOLD AUCAT ;- ERROR MODEL -- $ERROR IPRED = F IRES=IPRED-DV Y=IPRED * (1 + EPS(1)) + EPS(2) IWRES=IRES/(IPRED * EPS(1) + EPS(2)) TAT=A(4) AUCAT=A(5) TIS2 = A(2)/V2 TIS3 = A(3)/V3 Paul Hutson, PharmD, BCOP Professor UWisc School of Pharmacy T: 608.263.2496 F: 608.265.5421
