From: Mona.Alameddine

Date: Tue, 15 Dec 2009 14:53:50 +0100

Dear nmusers,

I am getting funny results when i add age as a covariate on oral clearance:

The OF decreases by 16 points,

but :

BSV on CL increases from 35% to 37%

BSV on V decreases from 49% to 47%

Intra-Individual variability decreases from 41% to 38%

And the most important is that the age had a positive effect on CL

Where CL INCREASED with age (THETA2 = -0.37 ). Age is not correlated

to other covariates and remained significant in the final model

together with the body weight.

I also tried several ways to test the effect of age , but NONMEM

didn't converge.

I also had funny results when i tried FOCE-I method, because i got a

very small variability on oral CL (0.7%) though i had much lower OF

(-55 points)

and the Covariance step failed.

I used the following:

$SUB ADVAN2 TRANS2

$PK

MAGE = 40 ; Median age

FAGE = (AGE-MAGE)/MAGE ; Fractional effect of age

TVCL = THETA(1)* (1- THETA(2)*FAGE)

CL = TVCL * EXP (ETA(1))

V = THETA(3)* EXP (ETA(2))

KA = THETA(4)

F1 = THETA(5)

S2=V/1000

$THETA (0,10)(0.5)(0,100)(0,0.6)(1 FIX)

$OMEGA 0.5 0.5

$ERROR

Y=F*EXP(ERR(1))

IPRED=F

IRES=DV-IPRED

W=F; if err prop W=F else W=1

IWRES=IRES/W

$SIGMA 0.5

$ESTIMATION SIGDIGITS=3 METHOD=1 MAXEVAL=9999 NOABORT POSTHOC PRINT=1

$TABLE UNCONDITIONAL ID TIME AMT CL V KA DV PRED IPRED IRES RES WRES IWRES

AGE SEX BW HGT ETA1 ETA2 EVID NOPRINT ONEHEADER FILE=run08.table.txt

Any suggestions on how to handle these results??

Thank you in advance for your help

Mona

Received on Tue Dec 15 2009 - 08:53:50 EST

Date: Tue, 15 Dec 2009 14:53:50 +0100

Dear nmusers,

I am getting funny results when i add age as a covariate on oral clearance:

The OF decreases by 16 points,

but :

BSV on CL increases from 35% to 37%

BSV on V decreases from 49% to 47%

Intra-Individual variability decreases from 41% to 38%

And the most important is that the age had a positive effect on CL

Where CL INCREASED with age (THETA2 = -0.37 ). Age is not correlated

to other covariates and remained significant in the final model

together with the body weight.

I also tried several ways to test the effect of age , but NONMEM

didn't converge.

I also had funny results when i tried FOCE-I method, because i got a

very small variability on oral CL (0.7%) though i had much lower OF

(-55 points)

and the Covariance step failed.

I used the following:

$SUB ADVAN2 TRANS2

$PK

MAGE = 40 ; Median age

FAGE = (AGE-MAGE)/MAGE ; Fractional effect of age

TVCL = THETA(1)* (1- THETA(2)*FAGE)

CL = TVCL * EXP (ETA(1))

V = THETA(3)* EXP (ETA(2))

KA = THETA(4)

F1 = THETA(5)

S2=V/1000

$THETA (0,10)(0.5)(0,100)(0,0.6)(1 FIX)

$OMEGA 0.5 0.5

$ERROR

Y=F*EXP(ERR(1))

IPRED=F

IRES=DV-IPRED

W=F; if err prop W=F else W=1

IWRES=IRES/W

$SIGMA 0.5

$ESTIMATION SIGDIGITS=3 METHOD=1 MAXEVAL=9999 NOABORT POSTHOC PRINT=1

$TABLE UNCONDITIONAL ID TIME AMT CL V KA DV PRED IPRED IRES RES WRES IWRES

AGE SEX BW HGT ETA1 ETA2 EVID NOPRINT ONEHEADER FILE=run08.table.txt

Any suggestions on how to handle these results??

Thank you in advance for your help

Mona

Received on Tue Dec 15 2009 - 08:53:50 EST