From: saik.urien.svp <*saik.urien*>

Date: Tue, 15 Dec 2009 16:57:47 +0100

Mona

Some observations:

1- Because your residual error is an exp or proportional model, it is

advised to use the INTER option (FOCEI)

2-The Omega structure seems unstable, because you have oral PK data, it is

likely that there is (are) some significant covariance term(s), at least

between CL and V. By taking this into account, the BSV on CL (under FOCEI)

will not be anymore near 0.

3-The BSV variations are not significant (+-2%)

4-To have some ideas about the effect of age in this context, info on the

size of the population, the age range, bodyweight range will be usefull

Saik

----- Original Message -----

From: <Mona.Alameddine

To: <nmusers

Sent: Tuesday, December 15, 2009 2:53 PM

Subject: [NMusers] Age effect on Clearance

*> 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 - 10:57:47 EST

Date: Tue, 15 Dec 2009 16:57:47 +0100

Mona

Some observations:

1- Because your residual error is an exp or proportional model, it is

advised to use the INTER option (FOCEI)

2-The Omega structure seems unstable, because you have oral PK data, it is

likely that there is (are) some significant covariance term(s), at least

between CL and V. By taking this into account, the BSV on CL (under FOCEI)

will not be anymore near 0.

3-The BSV variations are not significant (+-2%)

4-To have some ideas about the effect of age in this context, info on the

size of the population, the age range, bodyweight range will be usefull

Saik

----- Original Message -----

From: <Mona.Alameddine

To: <nmusers

Sent: Tuesday, December 15, 2009 2:53 PM

Subject: [NMusers] Age effect on Clearance

clearance:

Received on Tue Dec 15 2009 - 10:57:47 EST