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: robin.michelet > 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: owner-nmusers >> Behalf >> Of Robin Michelet >> Sent: Friday, August 6, 2021 3:38 PM >> To: nmusers >> 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/nmusers >> >> 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: robin.michelet >> www.clinical-pharmacy.eu >> https://fair-flagellin.eu/ >