If prior on CL is 13.8441, why initial value on 0.01 (etc.)? I would
start with prior values on all parameters.
Also, what is your indented use of
TVCL = THETA(1)*(WT/70)**0.75**ABCB
Why would ABCB1 affect dependence of WT on CL?
I think you need to fit the model with available data first (was it
done?) and then start from the solution with fixed population parameters
+ mixture model and include those with missing info (was it done?), and
only if this is working, attempt to combine mixture + priors, starting
from the final values of the simpler model.
Thank you
Leonid
On 3/15/2026 8:01 PM, Sam Liao wrote:
Try copilot or Gemini to resolve your coding issues.
Sam
On 03/15/2026 12:38 PM PDT Mohd Rahimi <[email protected]> wrote:
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*
