Dear NMUsers,
I would like advice in the best practice to use evid 0 before dosing,
which is to say an observation just before a dosing (*to estimate the
value in that compartment just before dosing event).
Thank you,
Carlos,
Using evid 0 before dosing
Hi Carlos,
It is commonly used. For most datasets, there will be at least one
observation that occurs before dosing to estimate the baseline value, and in
almost every scenario, the modeling dataset should mirror the real world
actions. So, there is no issue with it, and usually you will have an EVID=0
before the first dose.
Thanks,
Bill
Quoted reply history
-----Original Message-----
From: [email protected] <[email protected]> On Behalf
Of Carlos ST
Sent: Wednesday, November 6, 2019 10:03 AM
To: [email protected]
Subject: [NMusers] Using evid 0 before dosing
Dear NMUsers,
I would like advice in the best practice to use evid 0 before dosing, which
is to say an observation just before a dosing (*to estimate the value in
that compartment just before dosing event).
Thank you,
Carlos,
Dear Carlos,
You could also use an EVID=2 to do a read-out of a certain compartment.
Cheers,
Rob
-----Oorspronkelijk bericht-----
Quoted reply history
Van: owner-nmusers_at_globomaxnm.com <owner-nmusers_at_globomaxnm.com> Namens Bill Denney
Verzonden: woensdag 6 november 2019 16:12
Aan: Carlos ST <carlos.serra91_at_gmail.com>; nmusers_at_globomaxnm.com
Onderwerp: RE: [NMusers] Using evid 0 before dosing
Hi Carlos,
It is commonly used. For most datasets, there will be at least one observation that occurs before dosing to estimate the baseline value, and in almost every scenario, the modeling dataset should mirror the real world actions. So, there is no issue with it, and usually you will have an EVID=0 before the first dose.
Thanks,
Bill
-----Original Message-----
From: owner-nmusers_at_globomaxnm.com <owner-nmusers_at_globomaxnm.com> On Behalf Of Carlos ST
Sent: Wednesday, November 6, 2019 10:03 AM
To: nmusers_at_globomaxnm.com
Subject: [NMusers] Using evid 0 before dosing
Dear NMUsers,
I would like advice in the best practice to use evid 0 before dosing, which is to say an observation just before a dosing (*to estimate the value in that compartment just before dosing event).
Thank you,
Carlos,
De informatie in dit bericht is uitsluitend bestemd voor de geadresseerde. Aan dit bericht en de bijlagen kunnen geen rechten worden ontleend. Heeft u deze e-mail onbedoeld ontvangen? Dan verzoeken wij u het te vernietigen en de afzender te informeren. Openbaar maken, kopiëren en verspreiden van deze e-mail of informatie uit deze e-mail is alleen toegestaan met voorafgaande schriftelijke toestemming van de afzender. Het Radboudumc staat geregistreerd bij de Kamer van Koophandel in het handelsregister onder nummer 41055629.
The content of this message is intended solely for the addressee. No rights can be derived from this message or its attachments. If you are not the intended recipient, we kindly request you to delete the message and inform the sender. It is strictly prohibited to disclose, copy or distribute this email or the information inside it, without a written consent from the sender. Radboud university medical center is registered with the Dutch Chamber of Commerce trade register with number 41055629.
Bill
I think that the issue is more complicated than you acknowledge.
Assuming that the drug is not an endogenous substance, the pre-dose
concentration is likely to be BQL. However, there are two kinds of BQL values:
1. Samples that are truly zero because they were obtained pre-dose
2. Samples that are > 0 but < LOQ.
Yet both are reported as BQL.
From my perspective, a BQL value pre-dose provides no information to NONMEM.
Therefore, one should apply EVID=2 to that sample. This allows a prediction at
that timepoint but the sample does not influence the analysis.
Dennis
Dennis Fisher MD
P < (The "P Less Than" Company)
Phone / Fax: 1-866-PLessThan (1-866-753-7784)
www.PLessThan.com http://www.plessthan.com/
Quoted reply history
> On Nov 6, 2019, at 7:12 AM, Bill Denney <[email protected]> wrote:
>
> Hi Carlos,
>
> It is commonly used. For most datasets, there will be at least one
> observation that occurs before dosing to estimate the baseline value, and in
> almost every scenario, the modeling dataset should mirror the real world
> actions. So, there is no issue with it, and usually you will have an EVID=0
> before the first dose.
>
> Thanks,
>
> Bill
>
> -----Original Message-----
> From: [email protected] <[email protected]> On Behalf
> Of Carlos ST
> Sent: Wednesday, November 6, 2019 10:03 AM
> To: [email protected]
> Subject: [NMusers] Using evid 0 before dosing
>
> Dear NMUsers,
>
> I would like advice in the best practice to use evid 0 before dosing, which
> is to say an observation just before a dosing (*to estimate the value in
> that compartment just before dosing event).
>
> Thank you,
>
> Carlos,
>
Dear Carlos,
You could also use an EVID=2 to do a read-out of a certain compartment.
Cheers,
Rob
-----Oorspronkelijk bericht-----
Quoted reply history
Van: [email protected] <[email protected]> Namens Bill
Denney
Verzonden: woensdag 6 november 2019 16:12
Aan: Carlos ST <[email protected]>; [email protected]
Onderwerp: RE: [NMusers] Using evid 0 before dosing
Hi Carlos,
It is commonly used. For most datasets, there will be at least one observation
that occurs before dosing to estimate the baseline value, and in almost every
scenario, the modeling dataset should mirror the real world actions. So, there
is no issue with it, and usually you will have an EVID=0 before the first dose.
Thanks,
Bill
-----Original Message-----
From: [email protected] <[email protected]> On Behalf Of
Carlos ST
Sent: Wednesday, November 6, 2019 10:03 AM
To: [email protected]
Subject: [NMusers] Using evid 0 before dosing
Dear NMUsers,
I would like advice in the best practice to use evid 0 before dosing, which is
to say an observation just before a dosing (*to estimate the value in that
compartment just before dosing event).
Thank you,
Carlos,
De informatie in dit bericht is uitsluitend bestemd voor de geadresseerde. Aan
dit bericht en de bijlagen kunnen geen rechten worden ontleend. Heeft u deze
e-mail onbedoeld ontvangen? Dan verzoeken wij u het te vernietigen en de
afzender te informeren. Openbaar maken, kopiëren en verspreiden van deze e-mail
of informatie uit deze e-mail is alleen toegestaan met voorafgaande
schriftelijke toestemming van de afzender. Het Radboudumc staat geregistreerd
bij de Kamer van Koophandel in het handelsregister onder nummer 41055629.
The content of this message is intended solely for the addressee. No rights can
be derived from this message or its attachments. If you are not the intended
recipient, we kindly request you to delete the message and inform the sender.
It is strictly prohibited to disclose, copy or distribute this email or the
information inside it, without a written consent from the sender. Radboud
university medical center is registered with the Dutch Chamber of Commerce
trade register with number 41055629.
Hi Carlos,
Adding to what the others suggested, please note that, if that EVID=0
record is the very first record for that patient, NONMEM will predict
all compartments to be empty (all amounts = 0) at that time (unless you
initialise as discussed below).
If indeed there were no doses before that sample and therefore the
pre-dose sample is expected to contain no drug (it will come back as
undetectable, or BLQ), then I think you should just use it as a check,
but I would NOT fit that sample in the model, as it does not add much,
and it is possibly a bit tricky to implement in NONMEM due to the 0
predictions.
If, on the other hand, there were other doses before and the
concentration in that sample could be (or maybe it's even expected to
be) detectable, then you should fit that data point in the model.
For that to happen, though, NONMEM needs to be able to predict something
other than 0, in there, so you need to
1. either include in the dataset all the records for the previous doses
(preferred if the dosing history is available)
2. or initialise the system to some value.
For some ideas on approached for initialisation, you can have a look at
the paper below.
Dansirikul, C., Silber, H. E., & Karlsson, M. O. (2008). Approaches to
handling pharmacodynamic baseline responses. Journal of Pharmacokinetics
and Pharmacodynamics, 35(3), 269–283.
https://doi.org/10.1007/s10928-008-9088-2
Good luck.
Paolo
Quoted reply history
On 2019/11/06 17:48, Carlos ST wrote:
> Hi NMUsers community for you excellent suggestions. I will work through it.
> Thanks,
>
> Carlos
>
>
>
> On Wed, 6 Nov 2019 at 15:12, Bill Denney <[email protected]> wrote:
>> Hi Carlos,
>>
>> It is commonly used. For most datasets, there will be at least one
>> observation that occurs before dosing to estimate the baseline value, and in
>> almost every scenario, the modeling dataset should mirror the real world
>> actions. So, there is no issue with it, and usually you will have an EVID=0
>> before the first dose.
>>
>> Thanks,
>>
>> Bill
>>
>> -----Original Message-----
>> From: [email protected] <[email protected]> On Behalf
>> Of Carlos ST
>> Sent: Wednesday, November 6, 2019 10:03 AM
>> To: [email protected]
>> Subject: [NMusers] Using evid 0 before dosing
>>
>> Dear NMUsers,
>>
>> I would like advice in the best practice to use evid 0 before dosing, which
>> is to say an observation just before a dosing (*to estimate the value in
>> that compartment just before dosing event).
>>
>> Thank you,
>>
>> Carlos,
--
------------------------------------------------
Paolo Denti, PhD
A/Prof of Pharmacometrics
Division of Clinical Pharmacology
Department of Medicine
University of Cape Town
K45 Old Main Building
Groote Schuur Hospital
Observatory, Cape Town
7925 South Africa
phone: +27 21 404 7719
fax: +27 021 650 5410
email: [email protected]
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Dennis,
I may have to disagree, a little. There is information, a little, in a pre dose
BQL, about assay precision. I think you might agree that is a pre dose sample
is NOT BQL (which happens), tells you (and NONMEM) something about the assay.
Converse, even a BQL predose sample has a small amount of information.
That not withstanding, we also remove and pre-dose BQLs from the data set.
Mark Sale M.D.
Senior Vice President, Pharmacometrics
Nuventra Inc.
2525 Meridian Parkway, Suite 200
Durham, NC 27713
Phone (919)-973-0383
[email protected]<[email protected]>
CONFIDENTIALITY NOTICE The information in this transmittal (including
attachments, if any) may be privileged and confidential and is intended only
for the recipient(s) listed above. Any review, use, disclosure, distribution or
copying of this transmittal, in any form, is prohibited except by or on behalf
of the intended recipient(s). If you have received this transmittal in error,
please notify me immediately by reply email and destroy all copies of the
transmittal.
Quoted reply history
________________________________
From: [email protected] <[email protected]> on behalf of
Dennis Fisher <[email protected]>
Sent: Wednesday, November 6, 2019 7:23 AM
To: [email protected] <[email protected]>; Bill Denney
<[email protected]>
Cc: Carlos ST <[email protected]>; Steven Shafer
<[email protected]>
Subject: Re: [NMusers] Using evid 0 before dosing
WARNING: This email originated from outside of the company. Do not click links
or open attachments unless you recognize the sender and are expecting the
message.
Bill
I think that the issue is more complicated than you acknowledge.
Assuming that the drug is not an endogenous substance, the pre-dose
concentration is likely to be BQL. However, there are two kinds of BQL values:
1. Samples that are truly zero because they were obtained pre-dose
2. Samples that are > 0 but < LOQ.
Yet both are reported as BQL.
>From my perspective, a BQL value pre-dose provides no information to NONMEM.
>Therefore, one should apply EVID=2 to that sample. This allows a prediction
>at that timepoint but the sample does not influence the analysis.
Dennis
Dennis Fisher MD
P < (The "P Less Than" Company)
Phone / Fax: 1-866-PLessThan (1-866-753-7784)
http://www.plessthan.com/
On Nov 6, 2019, at 7:12 AM, Bill Denney
<[email protected]<mailto:[email protected]>> wrote:
Hi Carlos,
It is commonly used. For most datasets, there will be at least one
observation that occurs before dosing to estimate the baseline value, and in
almost every scenario, the modeling dataset should mirror the real world
actions. So, there is no issue with it, and usually you will have an EVID=0
before the first dose.
Thanks,
Bill
-----Original Message-----
From: [email protected]<mailto:[email protected]>
<[email protected]<mailto:[email protected]>> On Behalf
Of Carlos ST
Sent: Wednesday, November 6, 2019 10:03 AM
To: [email protected]<mailto:[email protected]>
Subject: [NMusers] Using evid 0 before dosing
Dear NMUsers,
I would like advice in the best practice to use evid 0 before dosing, which
is to say an observation just before a dosing (*to estimate the value in
that compartment just before dosing event).
Thank you,
Carlos,
Hi all
In theory a sample that has an expected concentration=0 and if you using an
additive error then this sample will provide information about \sigma_add.
However, this will only be the case if the assay result is reported exactly as
is (which would allow negative observations). However, since this is generally
not the case (i.e. the assay result is not reported exactly) then I agree it
will not provide useful information to the estimation process.
Cheers
Steve
………………………………………………………………………………………………………………………..……………………..………………………………………
Stephen
http://www.otago.ac.nz/pharmacy/people/profile/index.html?id=350 I
Professor of Clinical Pharmacy
Otago Pharmacometrics Group
School of Pharmacy | Te Kura Mātauraka Wai-whakaora
University of Otago | Te Whare Wānanga o Otāgo
Dunedin | Ōtepoti
Ph: 64 3 479 5099
Website | http://www.pharmacometrics.co.nz/
Quoted reply history
From: [email protected] <[email protected]> On Behalf Of
Dennis Fisher
Sent: Thursday, 7 November 2019 5:45 a.m.
To: Mark Sale <[email protected]>
Cc: [email protected]
Subject: Re: [NMusers] Using evid 0 before dosing
Mark
I disagree (more than a little). If a sample is reported as BQL and the
expected value is 0 (i.e., pre-dose, not endogenous), what information is there
about assay precision. If the error model is additive (or additive +
proportional), the sample will contribute zero to the objective function. If
the error model is proportional, NONMEM will report an error (0/0). I agree
that pre-dose samples > LOQ provide IMPORTANT information about assay precision.
Were you evacuated during the fires?
Dennis
Dennis Fisher MD
P < (The "P Less Than" Company)
Phone / Fax: 1-866-PLessThan (1-866-753-7784)
www.plessthan.com%2F&data=02%7C01%7Cstephen.duffull%40otago.ac.nz%7Cbacc42042d8942312bc608d762d97d4a%7C0225efc578fe4928b1579ef24809e9ba%7C1%7C0%7C637086558625087255&sdata=7yYTKHuQtvfdvaXYpZZBuRCO%2FaGLgYYmWy3sWhAdXEc%3D&reserved=0">https://apc01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.plessthan.com%2F&data=02%7C01%7Cstephen.duffull%40otago.ac.nz%7Cbacc42042d8942312bc608d762d97d4a%7C0225efc578fe4928b1579ef24809e9ba%7C1%7C0%7C637086558625087255&sdata=7yYTKHuQtvfdvaXYpZZBuRCO%2FaGLgYYmWy3sWhAdXEc%3D&reserved=0
On Nov 6, 2019, at 8:40 AM, Mark Sale
<[email protected]<mailto:[email protected]>> wrote:
Dennis,
I may have to disagree, a little. There is information, a little, in a pre dose
BQL, about assay precision. I think you might agree that is a pre dose sample
is NOT BQL (which happens), tells you (and NONMEM) something about the assay.
Converse, even a BQL predose sample has a small amount of information.
That not withstanding, we also remove and pre-dose BQLs from the data set.
Mark Sale M.D.
Senior Vice President, Pharmacometrics
Nuventra Inc.
2525 Meridian Parkway, Suite 200
Durham, NC 27713
Phone (919)-973-0383
[email protected]<x-msg://138/[email protected]>
CONFIDENTIALITY NOTICE The information in this transmittal (including
attachments, if any) may be privileged and confidential and is intended only
for the recipient(s) listed above. Any review, use, disclosure, distribution or
copying of this transmittal, in any form, is prohibited except by or on behalf
of the intended recipient(s). If you have received this transmittal in error,
please notify me immediately by reply email and destroy all copies of the
transmittal.
________________________________
From: [email protected]<mailto:[email protected]>
<[email protected]<mailto:[email protected]>> on behalf
of Dennis Fisher <[email protected]<mailto:[email protected]>>
Sent: Wednesday, November 6, 2019 7:23 AM
To: [email protected]<mailto:[email protected]>
<[email protected]<mailto:[email protected]>>; Bill Denney
<[email protected]<mailto:[email protected]>>
Cc: Carlos ST <[email protected]<mailto:[email protected]>>;
Steven Shafer <[email protected]<mailto:[email protected]>>
Subject: Re: [NMusers] Using evid 0 before dosing
WARNING: This email originated from outside of the company. Do not click links
or open attachments unless you recognize the sender and are expecting the
message.
Bill
I think that the issue is more complicated than you acknowledge.
Assuming that the drug is not an endogenous substance, the pre-dose
concentration is likely to be BQL. However, there are two kinds of BQL values:
1. Samples that are truly zero because they were obtained pre-dose
2. Samples that are > 0 but < LOQ.
Yet both are reported as BQL.
>From my perspective, a BQL value pre-dose provides no information to NONMEM.
>Therefore, one should apply EVID=2 to that sample. This allows a prediction
>at that timepoint but the sample does not influence the analysis.
Dennis
Dennis Fisher MD
P < (The "P Less Than" Company)
Phone / Fax: 1-866-PLessThan (1-866-753-7784)
www.plessthan.com%2F&data=02%7C01%7Cstephen.duffull%40otago.ac.nz%7Cbacc42042d8942312bc608d762d97d4a%7C0225efc578fe4928b1579ef24809e9ba%7C1%7C0%7C637086558625087255&sdata=7yYTKHuQtvfdvaXYpZZBuRCO%2FaGLgYYmWy3sWhAdXEc%3D&reserved=0">https://apc01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.plessthan.com%2F&data=02%7C01%7Cstephen.duffull%40otago.ac.nz%7Cbacc42042d8942312bc608d762d97d4a%7C0225efc578fe4928b1579ef24809e9ba%7C1%7C0%7C637086558625087255&sdata=7yYTKHuQtvfdvaXYpZZBuRCO%2FaGLgYYmWy3sWhAdXEc%3D&reserved=0
On Nov 6, 2019, at 7:12 AM, Bill Denney
<[email protected]<mailto:[email protected]>> wrote:
Hi Carlos,
It is commonly used. For most datasets, there will be at least one
observation that occurs before dosing to estimate the baseline value, and in
almost every scenario, the modeling dataset should mirror the real world
actions. So, there is no issue with it, and usually you will have an EVID=0
before the first dose.
Thanks,
Bill
-----Original Message-----
From: [email protected]<mailto:[email protected]>
<[email protected]<mailto:[email protected]>> On Behalf
Of Carlos ST
Sent: Wednesday, November 6, 2019 10:03 AM
To: [email protected]<mailto:[email protected]>
Subject: [NMusers] Using evid 0 before dosing
Dear NMUsers,
I would like advice in the best practice to use evid 0 before dosing, which
is to say an observation just before a dosing (*to estimate the value in
that compartment just before dosing event).
Thank you,
Carlos,