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 <[email protected]>
To: [email protected]
Sent: Thursday, June 18, 2015 9:35 AM
Subject: [NMusers] Estimation of Intake Time
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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, DiplPharmPharmacometrics GroupDivision of Clinical
PharmacologyDepartment of MedicineUniversity of Cape Town
