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