RE: [NMusers] Estimation of Intake Time

From: Andrzej Bienczak <andrzej.bienczak_at_googlemail.com>
Date: Thu, 18 Jun 2015 19:27:41 +0200

Thanks everyone for the tips!

 

I’m actually running a mixture model on ALAG like Jean =
suggested. Thought that would be a more robust way to distinguish =
between patients with correct and incorrect dosing history. NONMEM can =
allocate patients to a subpopulation with ALAG1 equal to either 0 or =
12h.

 

Depending on the run results I was planning on modifying the data set =
for the flagged patients similar to Emmanuel’s suggestions.

 

I forgot to mention that the model was first developed based on =
intensive data only (data with observed intake) and it already has a =
transit model for the delay in the absorption with BOV added on the MTT. =


 

Regards,

 

Andrzej

 

 

From: Lavigne, Jean [mailto:jean.lavigne_at_celerion.com]
Sent: 18 June 2015 06:07 PM
To: Emmanuel Chigutsa; Andrzej Bienczak; nmusers_at_globomaxnm.com
Subject: RE: [NMusers] Estimation of Intake Time

 

Dear Andrej,

 

Perhaps, you may want to consider using a mixture model for the =
introduction or not of a 12 hours lag time difference. This way NONMEM =
would estimate for you if the ALAG was 0 or 12.

 

Best regards,

 

Jean

 

________________________________________________________________

Jean R. Lavigne, M.Sc. │Associate Director, Clinical =
Pharmacology

Celerion

100 Boul. Alexis-Nihon, Suite 360│St-Laurent QC│H4M 2N8 =
Canada

T: +1 514 744 8726│F: + 1 514 744-8700

jean.lavigne_at_celerion.com <mailto:jean.lavigne_at_celerion.com> =
│www.celerion.com

 <http://www.linkedin.com/company/celerion?trk=company_logo> =
<http://www.youtube.com/user/CelerionCRO>

 

Celerion Expands Belfast Facility with Containment Room to Enable Live =
Biologics and Vaccine Studies =
<http://celerion.com/news/2013/06/04/celerion-expands-belfast-facility-wi=
th-containment-room-to-enable-live-biologics-and-vaccine-studies> .

Celerion Builds on Respiratory Capabilities With the Addition of an =
On-site Bronchoscopy =
<http://celerion.com/news/2013/01/09/bronchoscopy-suite> Suite.

 

From: owner-nmusers_at_globomaxnm.com <mailto:owner-nmusers_at_globomaxnm.com> =
 [mailto:owner-nmusers_at_globomaxnm.com] On Behalf Of Emmanuel Chigutsa
Sent: Thursday, June 18, 2015 11:42 AM
To: Andrzej Bienczak; nmusers_at_globomaxnm.com =
<mailto:nmusers_at_globomaxnm.com>
Subject: Re: [NMusers] Estimation of Intake Time

 

Hi Andrej,

You can try something along the following lines:

-subtract 12 hours from the time of all doses in the dataset (create new =
time column)

-add a fixed ALAG of 12 hours and some variability on it. You could also =
fix the variability to a big number. You can also test covariates =
(patient subgroups) on this ALAG.

 

Good luck,

Mannie

 

  _____

From: Andrzej Bienczak <andrzej.bienczak_at_googlemail.com =
<mailto:andrzej.bienczak_at_googlemail.com> >
To: nmusers_at_globomaxnm.com <mailto:nmusers_at_globomaxnm.com>
Sent: Thursday, June 18, 2015 9:35 AM
Subject: [NMusers] Estimation of Intake Time

 

Dear NMusers,

 

I would like to present you with a problem that some of you might have =
faced before. I am currently building a PK model for a drug with once =
daily oral administration. The drug has a long half-life and can be =
taken either in the morning or at night. Unfortunately due to lack of =
consistency in the recording of the administration times by the study =
team part of the patients flagged to have taken the medication in the =
mornings were in fact taking it at night (i.e. 08:25 corresponds to =
20:25 the previous day). At this stage there is no way of tracking back =
what the correct intake times were.

 

The data consists of 2 sparse measurements per patient and indeed =
looking at individual profiles you can clearly see that some samples are =
from the elimination phase, indicating the drug was taken more than 12h =
prior. I could correct the dataset based on an empirical judgement =
backed up by the visual analysis but I was hoping there would be a more =
robust way.

 

Is there any way to put a THETA on the dosage time for those patients to =
let NONMEM estimate a corrected administration time?

 

I tried simply adding an extra parameter on the intake time for those =
patients (placed the code in $PK):

IF(FLAG_AM.EQ.1) TIME=TIME-THETA(17)

 

But received the following error message:

 

AN ERROR WAS FOUND IN THE CONTROL STATEMENTS.

 AN ERROR WAS FOUND ON LINE 30 AT THE APPROXIMATE POSITION NOTED:

    IF(FLAG_AM.EQ.1) TIME=TIME-THETA(17)

                     X

 THE CHARACTERS IN ERROR ARE: TIME

236 DATA ITEM MAY NOT BE CHANGED WITH THIS VALUE OF ICALL.

 

 

I would be grateful for some suggestions on how to deal with this issue.

 

Regards,

 

Andrzej

 

 

Andrzej Bienczak

MSc, MPharm, DiplPharm

Pharmacometrics Group

Division of Clinical Pharmacology

Department of Medicine

University of Cape Town

 

 

 


This electronic transmission may contain confidential and/or proprietary =
information and is intended to be for the use of the individual or =
entity named above. If you are not the intended recipient, be aware that =
any disclosure, copying, distribution or use of the contents of this =
electronic transmission is prohibited. If you have received this =
electronic transmission in error, please destroy it and immediately =
notify us of the error. Thank you.






image001.png
(image/png attachment: image001.png)

image002.png
(image/png attachment: image002.png)

Received on Thu Jun 18 2015 - 13:27:41 EDT

This archive was generated by hypermail 2.3.0 : Fri Sep 27 2019 - 16:44:47 EDT