# RE: help on diagnostic of a problem -- about M3 method for LLOQ:

From: Ahn, Jae Eun <jaeeun.ahn>
Date: Thu, 11 Feb 2010 12:06:49 -0500

Dear Ethan,

The denominator of DUM should be in the standard deviation level, not
variance, so it should be

W = =
SQRT(THETA(7)**2*FLAG+THETA(8)**2*(1-FLAG)+THETA(9)**2*IPRED**2)

IF (TYPE.EQ.2.AND.CMT.EQ.2) DUM=(LOQ-IPRED)/W

Note that the way you coded DUM is equivalent to DUM=(LOQ-IPRED)/W**2

In your code for log-transformed data, I see that the denominator is
specified as a standard deviation.

However, it is not clear to me whether you want to use a different
magnitude of proportional error or additive error for studies whose
number is greater than 3. In the code for natural DV, THETA(8) is for
the different additive error of such studies, whereas THETA(8) in the
log DV corresponds to the different proportional error.

Best regards,

Jae Eun

________________________________

From: owner-nmusers
On Behalf Of Ethan Wu
Sent: Thursday, February 11, 2010 10:53 AM
To: nmusers
Subject: [NMusers] 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*IPRE=
D
**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

Received on Thu Feb 11 2010 - 12:06:49 EST

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