From: Ethan Wu <*ethan.wu75*>

Date: Thu, 11 Feb 2010 10:40:40 -0800 (PST)

ominator to be variance. after changing it, the model works fine n=

ow. I meant to have different additive error for study greater=

than 3. When I used log transformed data, I didn't see the need to have co=

mbination error model, but, I still kept estimating different err for studi=

es. ________________________________ From: "Ahn, Jae Eun" <jaeeun=

.ahn

com Sent: Thu, February 11, 2010 12:06:49 PM Subject: RE: [NMusers] hel=

p on diagnostic of a problem -- about M3 method for LLOQ: Dear Etha=

n, The denominator of DUM should be in the standard deviation level=

, not variance, so it should be W = SQRT(THETA(7)**2*FLAG+T=

HETA(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 D=

UM=(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 pro=

portional 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 differe=

nt proportional error. Best regards, Jae Eun _________=

_______________________ From:owner-nmusers

r-nmusers

11, 2010 10:53 AM To: nmusers

diagnostic of a problem -- about M3 method for LLOQ: Dear users,=

his error message: 0PROGRAM TERMINATED BY OBJ ERROR IN CLIK WITH INDIVI=

DUAL 2 ID=0.19000000E+02 CONDITIONAL LIKELIHOOD FOR SOME OBSERVATION ES=

TIMATED TO BE NEGLIGIBLE note that ID 19 is the first subject in th=

e dataset. this is how I specify the $ERR (a combinative erro) and $EST:=

S = 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)=

) THEN F_FLAG=0 Y = IPRED+W*EPS(1) ENDIF $ESTIMATION MET=

HOD=1 LAPLACIAN MAXEVAL=9999 PRINT=10 NOABORT or this: $ESTIM=

ATION METHOD=1 INT LAPLACIAN MAXEVAL=9999 PRINT=10 NOABORT __=

___ Interstingly, when I use Log-transformed data, the model would run fi=

ne. this is how I specify $ERR (an additive error) and $EST, all the othe=

r 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=

DEL1=0 IF(W.EQ.0)DEL1=1 IWRES = IRES/( W+DEL=

1 ) IF (TYPE.EQ.2.AND.CMT.EQ.2) DUM = (LOG(LOQ)-IPRED)/(THETA(7)*FLA=

G+THETA(8)*(1-FLAG)) CUMD=PHI(DUM) IF (TYPE.EQ.2) THEN F_FLA=

G=1 Y=CUMD ENDIF IF (TYPE.EQ.1) THEN F_FLAG=0 Y=IPRED +=

EPS(1)* W ENDIF $ESTIMATION METHOD=1 LAPLACIAN MAXEVAL=9999 P=

RINT=10 NOABORT

Received on Thu Feb 11 2010 - 13:40:40 EST

Date: Thu, 11 Feb 2010 10:40:40 -0800 (PST)

ominator to be variance. after changing it, the model works fine n=

ow. I meant to have different additive error for study greater=

than 3. When I used log transformed data, I didn't see the need to have co=

mbination error model, but, I still kept estimating different err for studi=

es. ________________________________ From: "Ahn, Jae Eun" <jaeeun=

.ahn

com Sent: Thu, February 11, 2010 12:06:49 PM Subject: RE: [NMusers] hel=

p on diagnostic of a problem -- about M3 method for LLOQ: Dear Etha=

n, The denominator of DUM should be in the standard deviation level=

, not variance, so it should be W = SQRT(THETA(7)**2*FLAG+T=

HETA(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 D=

UM=(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 pro=

portional 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 differe=

nt proportional error. Best regards, Jae Eun _________=

_______________________ From:owner-nmusers

r-nmusers

11, 2010 10:53 AM To: nmusers

diagnostic of a problem -- about M3 method for LLOQ: Dear users,=

his error message: 0PROGRAM TERMINATED BY OBJ ERROR IN CLIK WITH INDIVI=

DUAL 2 ID=0.19000000E+02 CONDITIONAL LIKELIHOOD FOR SOME OBSERVATION ES=

TIMATED TO BE NEGLIGIBLE note that ID 19 is the first subject in th=

e dataset. this is how I specify the $ERR (a combinative erro) and $EST:=

S = 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)=

) THEN F_FLAG=0 Y = IPRED+W*EPS(1) ENDIF $ESTIMATION MET=

HOD=1 LAPLACIAN MAXEVAL=9999 PRINT=10 NOABORT or this: $ESTIM=

ATION METHOD=1 INT LAPLACIAN MAXEVAL=9999 PRINT=10 NOABORT __=

___ Interstingly, when I use Log-transformed data, the model would run fi=

ne. this is how I specify $ERR (an additive error) and $EST, all the othe=

r 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=

DEL1=0 IF(W.EQ.0)DEL1=1 IWRES = IRES/( W+DEL=

1 ) IF (TYPE.EQ.2.AND.CMT.EQ.2) DUM = (LOG(LOQ)-IPRED)/(THETA(7)*FLA=

G+THETA(8)*(1-FLAG)) CUMD=PHI(DUM) IF (TYPE.EQ.2) THEN F_FLA=

G=1 Y=CUMD ENDIF IF (TYPE.EQ.1) THEN F_FLAG=0 Y=IPRED +=

EPS(1)* W ENDIF $ESTIMATION METHOD=1 LAPLACIAN MAXEVAL=9999 P=

RINT=10 NOABORT

Received on Thu Feb 11 2010 - 13:40:40 EST