help on diagnostic of a problem -- about M3 method for LLOQ:
Dear users,
I am working on a dataset with not small percentage below LLOQ.
when I implemented M3 method to account for this, I always getting this error
message:
0PROGRAM TERMINATED BY OBJ
ERROR IN CLIK WITH INDIVIDUAL 2 ID=0.19000000E+02
CONDITIONAL LIKELIHOOD FOR SOME OBSERVATION ESTIMATED TO BE NEGLIGIBLE
note that ID 19 is the first subject in the dataset.
this is how I specify the $ERR (a combinative erro) and $EST:
__________
$ERROR
IPRED = F
IRES = DV-IPRED
FLAG=1
IF(STDY.GT.3) FLAG=0
DEL=0
W = SQRT(THETA(7)**2*FLAG+THETA(8)**2*(1-FLAG)+THETA(9)**2*IPRED**2)
IF(W.EQ.0)DEL=1
IWRES = IRES/(W+DEL)
IF (TYPE.EQ.2.AND.CMT.EQ.2)
DUM=(LOQ-IPRED)/(THETA(7)**2*FLAG+THETA(8)**2*(1-FLAG)+THETA(9)**2*IPRED**2)
CUMD=PHI(DUM)
IF (TYPE.EQ.2) THEN
F_FLAG=1
Y=CUMD
ENDIF
IF (TYPE.EQ.1) THEN
F_FLAG=0
Y = IPRED+W*EPS(1)
ENDIF
$ESTIMATION METHOD=1 LAPLACIAN MAXEVAL=9999 PRINT=10 NOABORT
or this:
$ESTIMATION METHOD=1 INT LAPLACIAN MAXEVAL=9999 PRINT=10 NOABORT
_____
Interstingly, when I use Log-transformed data, the model would run fine. this
is how I specify $ERR (an additive error) and $EST, all the other aspects of
model are the same between two tries.
Could someone help me understand what is happening? Thanks.
_____
$ERROR
DEL = 0
IF(F.LE.0) DEL = 1
IPRED = LOG(F+DEL)
IRES = DV-IPRED
FLAG=1
IF(STDY.GT.3) FLAG=0
W = SQRT(THETA(7)**2*FLAG+THETA(8)**2*(1-FLAG))
DEL1=0
IF(W.EQ.0)DEL1=1
IWRES = IRES/(W+DEL1)
IF (TYPE.EQ.2.AND.CMT.EQ.2) DUM =
(LOG(LOQ)-IPRED)/(THETA(7)*FLAG+THETA(8)*(1-FLAG))
CUMD=PHI(DUM)
IF (TYPE.EQ.2) THEN
F_FLAG=1
Y=CUMD
ENDIF
IF (TYPE.EQ.1) THEN
F_FLAG=0
Y=IPRED +EPS(1)*W
ENDIF
$ESTIMATION METHOD=1 LAPLACIAN MAXEVAL=9999 PRINT=10 NOABORT