Mixed Models

On Wed, Mar 21, 2012 at 10:39 AM, Shankar Lanke <[email protected]>wrote: > Dear All, > > I am running a pop pk IV infusion data, the observed values are collected > form obese patients and normal patients. > I used WINONLIN to estimate the initial parameters. Patients who weigh > more than 350 lbs are following 2CM and less than 350 are following 1CM. > I confirmed the models based on AIC, CV% (of parameters), graphical > representation. Vd increases with weight (1CM). > > So I used IF(WT<=350)THEN statements from the beginning ($MODEL, $ PK, $ > DES, $THETA). I have the following error. > AN ERROR WAS FOUND IN THE CONTROL STATEMENTS. > > AN ERROR WAS FOUND ON LINE 10 AT THE APPROXIMATE POSITION NOTED: > IF(WT<=350)THEN > X > THE CHARACTERS IN ERROR ARE: IF > > Thank you very much in advance for your suggestions. > > > Regards, > Shankar Lanke Ph.D. > > -- Indrajeet Singh,PhD Sr. Clinical Pharmacokineticist Abbott Labs, North Chicago, IL

On a more practical note, the apparent WT dependence of the disposition model might disappear if you use normal fat mass instead of total body WT to scale the PK parameters (see Anderson & Holford 2009) Nick Anderson BJ, Holford NHG. Mechanistic basis of using body size and maturation to predict clearance in humans. Drug Metab Pharmacokinet 2009; 24: 25-36. On 21/03/2012 5:22 p.m., indrajeet singh wrote: > Shankar: > > I hope you are not, but you can not change true value variables in conditional statements > > eg. > IF (...) THEN > CL= TVCL+eta(1) > ELSE > CL=TVCL+eta(2) > ENDIF > > There are alternate ways of doing that by creating new identifier for your WT ranges. > > I hope this helps. > > On Wed, Mar 21, 2012 at 10:39 AM, Shankar Lanke < [email protected] < mailto: [email protected] >> wrote: > > Dear All, > > I am running a pop pk IV infusion data, the observed values are > collected form obese patients and normal patients. > I used WINONLIN to estimate the initial parameters. Patients who > weigh more than 350 lbs are following 2CM and less than 350 are > following 1CM. I confirmed the models based on AIC, CV% (of > parameters), graphical representation. Vd increases with weight (1CM). > > So I used IF(WT<=350)THEN statements from the beginning ($MODEL, $ > PK, $ DES, $THETA). I have the following error. > AN ERROR WAS FOUND IN THE CONTROL STATEMENTS. > AN ERROR WAS FOUND ON LINE 10 AT THE APPROXIMATE POSITION NOTED: > IF(WT<=350)THEN > X > THE CHARACTERS IN ERROR ARE: IF > > Thank you very much in advance for your suggestions. > > Regards, > Shankar Lanke Ph.D. > > -- > Indrajeet Singh,PhD > Sr. Clinical Pharmacokineticist > Abbott Labs, North Chicago, IL -- Nick Holford, Professor Clinical Pharmacology Dept Pharmacology& Clinical Pharmacology, Bldg 505 Room 202D University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53 email: [email protected] http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford First World Conference on Pharmacometrics, 5-7 September 2012 Seoul, Korea http://www.go-wcop.org

On Wed, Mar 21, 2012 at 3:47 PM, Nick Holford <[email protected]>wrote: > Hi, > > I don't really understand the post from Indrajeet (what is a 'true' > value?). > > The following code is legal in NM7: > > IF (WT<=350) THEN > CL=THETA(1) + ETA(1) > ELSE > CL=THETA(1) + ETA(2) > ENDIF > > but won't work in NMVI where you have to use f77 syntax for logical > expressions: > > IF (WT.LE.350) THEN > CL=THETA(1) + ETA(1) > ELSE > CL=THETA(1) + ETA(2) > ENDIF > > Perhaps Shankar is using NMVI? > > On a more practical note, the apparent WT dependence of the disposition > model might disappear if you use normal fat mass instead of total body WT > to scale the PK parameters (see Anderson & Holford 2009) > > Nick > > Anderson BJ, Holford NHG. Mechanistic basis of using body size and > maturation to predict clearance in humans. Drug Metab Pharmacokinet 2009; > 24: 25-36. > > > > On 21/03/2012 5:22 p.m., indrajeet singh wrote: > >> Shankar: >> >> I hope you are not, but you can not change true value variables in >> conditional statements >> eg. >> IF (...) THEN >> CL= TVCL+eta(1) >> ELSE >> CL=TVCL+eta(2) >> ENDIF >> >> There are alternate ways of doing that by creating new identifier for >> your WT ranges. >> >> I hope this helps. >> >> >> >> >> On Wed, Mar 21, 2012 at 10:39 AM, Shankar Lanke >> <[email protected]<mailto: >> [email protected]**>> wrote: >> >> Dear All, >> >> I am running a pop pk IV infusion data, the observed values are >> collected form obese patients and normal patients. >> I used WINONLIN to estimate the initial parameters. Patients who >> weigh more than 350 lbs are following 2CM and less than 350 are >> following 1CM. I confirmed the models based on AIC, CV% (of >> parameters), graphical representation. Vd increases with weight (1CM). >> >> So I used IF(WT<=350)THEN statements from the beginning ($MODEL, $ >> PK, $ DES, $THETA). I have the following error. >> AN ERROR WAS FOUND IN THE CONTROL STATEMENTS. >> AN ERROR WAS FOUND ON LINE 10 AT THE APPROXIMATE POSITION NOTED: >> IF(WT<=350)THEN >> X >> THE CHARACTERS IN ERROR ARE: IF >> >> Thank you very much in advance for your suggestions. >> >> >> Regards, >> Shankar Lanke Ph.D. >> >> >> >> >> -- >> Indrajeet Singh,PhD >> Sr. Clinical Pharmacokineticist >> Abbott Labs, North Chicago, IL >> >> > -- > Nick Holford, Professor Clinical Pharmacology > Dept Pharmacology& Clinical Pharmacology, Bldg 505 Room 202D > University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand > tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53 > email: [email protected] > http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford > > First World Conference on Pharmacometrics, 5-7 September 2012 > Seoul, Korea http://www.go-wcop.org > > > -- Regards, Shankar Lanke Ph.D. Assistant Professor Department of Pharmaceutical Sciences College of Pharmacy The University of Findlay (C) 678-232-3567 (O) 419-434-5448 Fax# 419-434-4390