Re: [NMusers] Time-varying input/flexibility to change input rate on the fly
ind 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.miche...@fu-berlin.de > 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-nmus...@globomaxnm.com On > Behalf > > Of Robin Michelet > > Sent: Friday, August 6, 2021 3:38 PM > > To: nmusers@globomaxnm.com > > 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@globomaxnm.com/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: robin.miche...@fu-berlin.de > > www.clinical-pharmacy.eu > > https://fair-flagellin.eu/ > > -- Eliford Ngaimisi Kitabi Pharmacometrician, FDA mobile: +2405477565 Joy is my target
Re: [NMusers] Time-varying input/flexibility to change input rate on the fly
one can do it by hands, like set F1=1 and then use DA1/dt = -KA*A(1) DA2/dt = FF1(any function of time)*A(1) .. will it do the trick? Leonid 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.miche...@fu-berlin.de 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-nmus...@globomaxnm.com On Behalf Of Robin Michelet Sent: Friday, August 6, 2021 3:38 PM To: nmusers@globomaxnm.com 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@globomaxnm.com/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: robin.miche...@fu-berlin.de www.clinical-pharmacy.eu https://fair-flagellin.eu/
Re: [NMusers] Time-varying input/flexibility to change input rate on the fly
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.miche...@fu-berlin.de 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-nmus...@globomaxnm.com On Behalf Of Robin Michelet Sent: Friday, August 6, 2021 3:38 PM To: nmusers@globomaxnm.com 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@globomaxnm.com/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: robin.miche...@fu-berlin.de www.clinical-pharmacy.eu https://fair-flagellin.eu/
RE: [NMusers] Time-varying input/flexibility to change input rate on the fly
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-nmus...@globomaxnm.com On Behalf Of Robin Michelet Sent: Friday, August 6, 2021 3:38 PM To: nmusers@globomaxnm.com 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@globomaxnm.com/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: robin.miche...@fu-berlin.de www.clinical-pharmacy.eu https://fair-flagellin.eu/
[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@globomaxnm.com/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: robin.miche...@fu-berlin.de www.clinical-pharmacy.eu https://fair-flagellin.eu/
