Re: Time-varying input/flexibility to change input rate on the fly

On 8/6/2021 4:20 PM, Robin Michelet wrote: > Hi Bill, > > Thank you for your quick answer. As far as I understand Nonmem's inner workings, bio availability is only applied at the onset of dosing and adding variability on it would not be able to capture a transient change in input. For example in the case of a patch, if it would detach partly during the dosing interval one would still need an input (i.e. infusion-style input in the depot) but it would just be lower than before. Changing F1 would in this case not do much right? > > Kind regards, > > Robin > > Dr. ir. Robin Michelet > Senior scientist > > Freie Universitaet Berlin > Institute of Pharmacy > Dept. of Clinical Pharmacy & Biochemistry > Kelchstr. 31 > 12169 Berlin > Germany > Phone: + 49 30 838 50659 > Fax: + 49 30 838 4 50656 > Email: [email protected] > www.clinical-pharmacy.eu > https://fair-flagellin.eu/ > > On 06-08-21 10:15 PM, Bill Denney wrote: > > > Hi Robin, > > > > I don't think that I've seen an update. That said, the need I had then was for a very specific need for an unusual drug. I've only seen this type of > > > > issue once where it seemed to need time-dependent effects. Generally, > > > > effects similar-- but not identical-- to what I was experiencing at the time > > > > are better-modeled with simpler systems. For example, adsorption to > > > > infusion sets can almost always be modeled as a decrease in bioavailability > > > > and/or a lag time (it's not typically time-dependent behavior). > > > > I would assume that loss of part of a tablet or detachment of a patch could > > > > be simply modeled as random variability (or a fixed effect) on > > bioavailability. Random pump malfunction would depend on how it > > > > malfunctioned, but I would be wary of trying to model random effects as this > > > > more complex time-dependent bioavailability unless you had data on the > > malfunction method-- in which case I would suggest putting it into the > > dataset as a different dosing record. > > > > Thanks, > > > > Bill > > > > -----Original Message----- > > > > From: [email protected] < [email protected] > On Behalf > > > > Of Robin Michelet > > Sent: Friday, August 6, 2021 3:38 PM > > To: [email protected] > > Subject: [NMusers] Time-varying input/flexibility to change input rate on > > the fly > > > > Dear all, > > > > I was wondering if any progress has been made on the topic raised originally > > > > by Bill Denney in 2018: > > > > https://www.mail-archive.com/[email protected]/msg06990.html > > > > Are there any simpler ways in NM 7.5 to adapt input (e.g. infusion > > rates) in $DES during the integration step without adapting the dataset > > itself? I.e. to model the malfunctioning of an infusion pump (at random), > > the loss of part of a tablet, or the detachment of a patch? > > > > Thank you! I could not answer to the original topic which is why I just > > linked to it. > > > > -- > > Dr. ir. Robin Michelet > > Senior scientist > > > > Freie Universitaet Berlin > > Institute of Pharmacy > > Dept. of Clinical Pharmacy & Biochemistry Kelchstr. 31 > > 12169 Berlin > > Germany > > Phone: + 49 30 838 50659 > > Fax: + 49 30 838 4 50656 > > Email: [email protected] > > www.clinical-pharmacy.eu > > https://fair-flagellin.eu/