Re: [NMusers] $PRIOR and $MIX for ABCB1 3435 and 2677 data

[Jeroen Elassaiss-Schaap (PD-value B.V.)]

Dear Mohd, This one I am not sure about but you might want to try use the mixnum in every of the four IF statements. This way there may be a gradient for all subjects. Please refer to our model at https://ascpt.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fpsp4.12140&file=psp412140-sup-0001-suppinfoS01.docx for an example that did work with mixnum and a covariate driven assignment together.  I do not know about the impact of using a prior in this setting. An option would be to first test without. Hope this helps, Jeroen http://pd-value.com jer...@pd-value.com @PD_value +31 6 23118438 -- More value out of your data! Op 15 mrt 2026 om 20:49 heeft Mohd Rahimi <rahimi1...@gmail.com> het volgende geschreven:  Greetings, I have a rifampicin PK dataset combining sparse and rich sampling data. The dataset includes ABCB1 3435 and 2677 genotype information, but these data are available only for 70 individuals in the sparse-sampling group, while the remaining 46 individuals in the rich-sampling group have missing genotype data. I attempted to use $PRIOR and $MIX to quantify the effects of ABCB1 3435 and 2677 on the PK parameters of rifampicin, but I am currently encountering a zero-gradient issue. The results are as follows. 0ITERATION NO.:    2    OBJECTIVE VALUE:   273052.291852277        NO. OF FUNC. EVALS.:   0  CUMULATIVE NO. OF FUNC. EVALS.:       30  NPARAMETR:  1.0000E-02  1.0000E-02  1.0000E-02  1.0000E-02  1.0000E-02  1.0000E-02  1.0000E-01  1.0000E-02  1.0000E-02  1.0000E-02              1.0000E-02  PARAMETER:  1.0000E-01  1.0000E-01  1.0000E-01  1.0000E-01  1.0000E-01  1.0000E-01  1.0000E-01  1.0000E-01  1.0000E-01  1.0000E-01              1.0000E-01  GRADIENT:  -3.9851E+04 -1.2262E+04  5.1571E+04 -1.9717E+03 -2.1652E+05 -1.6134E+04 -8.0853E+01         NaN         NaN         NaN and the code I am using: $INPUT      ID TIME AMT ODV DV BLQ MDV EVID CMT OCC ABCB11 MISS ABCB12 MDR12 ABCB13 RACE AGE CXR_BASE GENDER WT SMOK $DATA      RIF_NEW_02_PGX03.csv IGNORE=# $SUBROUTINE ADVAN2 TRANS2 $PRIOR NWPRI $PK EST = MIXEST IF(MISS.EQ.0.AND.ABCB11.LE.2) ABCB = 1 IF(MISS.EQ.0.AND.ABCB11.EQ.3) ABCB = 0 IF(MISS.EQ.1.AND.MIXNUM.EQ.1) ABCB = 1 IF(MISS.EQ.1.AND.MIXNUM.EQ.2) ABCB = 0    TVCL = THETA(1)*(WT/70)**0.75**ABCB    TVV = THETA(2)*(WT/70)**1    TVKA = THETA(3)    TVALAG1 = THETA(4)    CL = TVCL*EXP(ETA(1))     V = TVV*EXP(ETA(2))    KA = TVKA*EXP(ETA(3))    ALAG1 = TVALAG1*EXP(ETA(4))  S2 = V $MIX NSPOP = 2 P(1) = THETA(7) P(2) = 1-P(1) $ERROR IPRED = LOG(F + 0.000001) IRES = DV-IPRED W = SQRT(THETA(5)**2 + (THETA(6)/F)**2) IF(W.EQ.0) W = 1 IWRES = IRES/W Y = IPRED + W*EPS(1) $THETA    (0,0.01) ; TVCL  (0,0.01) ; TVV  (0,0.01) ; TVKA  (0,0.01) ; ALAG1  (0,0.01) ; PROPRUV  (0,0.01) ; ADDRUV  (0,0.1)    ; P (1)  ;(0,0.001)    ; ABCB $OMEGA 0.01  ; BSVCL (initial estimate) 0.01  ; BSVV 0.01  ; BSVKA 0.01  ; ALAG1 $SIGMA  1 FIX  ; ADDRUV (initial estimate) $THETAP 13.8441 FIX     ; PRIOR OF Cl $THETAP 76.3173 FIX     ; PRIOR OF Vd $THETAP 0.95741 FIX     ; PRIOR OF Ka ;$THETAP 0.11603 FIX     ; PRIOR OF Tlag $THETAPV 0.1806 FIX ; PRIOR UNCERTAINTY - Cl $THETAPV 0.2489 FIX ; PRIOR UNCERTAINTY - Vd $THETAPV 1.2538 FIX ; PRIOR UNCERTAINTY - Ka ;$THETAPV 0.1183 FIX ; PRIOR UNCERTAINTY - Tlag $ESTIMATION METHOD=COND INTER SIGDIGITS=3 MAXEVAL=9999 PRINT=1 NOABORT $COVARIANCE MATRIX=R ; COVARIANCE STEP $TABLE ID TIME DV IPRED CWRES WRES IWRES PRED NOPRINT ONEHEADER FILE=sdtab560 $TABLE ID TIME DV ETA(1) ETA(2) ETA(3) NOPRINT ONEHEADER FILE=patab560 $TABLE ID TIME AMT ODV DV BLQ MDV EVID CMT OCC ABCB11 MISS ABCB12 MDR12 ABCB13 RACE AGE CXR_BASE GENDER WT SMOK KA CL V NOPRINT ONEHEADER FILE=xptab560 Any input or suggestions would be greatly appreciated, as I have been trying to resolve this issue for several weeks. Thank you. MOHD. RAHIMI BIN MUDA