Dear Group members,
I have recently started using NONMEM for population analysis.
I need you help in understanding Bayesian estimation using NONMEM.
Can any body provide me a sample control stream along with data file
(Excel or csv format) and also explain the output.
I use Visual NM to run NONMEM version V.
Thanking you in anticipation.
Regards
Tausif Ahmed Ph.D.
Metabolism and Pharmacokinetics Department
Ranbaxy Research Lab
India
(i) The information contained in this e-mail message is intended only for the
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Departmental.gif
Description:
Departmental.gif
Bayesian estimation example
Tausif,
Why do you want to use Bayesian Estimation? If you have only just started to
use NONMEM then perhaps you have misunderstood the reasons for using it. It is
very rarely needed.
Nick
> Dear Group members,
>
> I have recently started using NONMEM for population analysis.
> I need you help in understanding Bayesian estimation using NONMEM.
> Can any body provide me a sample control stream along with data file (Excel
> or csv format) and also explain the output.
> I use Visual NM to run NONMEM version V.
>
> Thanking you in anticipation.
>
> Regards
> Tausif Ahmed Ph.D.
> Metabolism and Pharmacokinetics Department
> Ranbaxy Research Lab
> India
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
email:[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
Hello Tausif
Please visit ( http://www.accp1.org/ <BLOCKED:: http://www.accp1.org/> )
and click on Pharmacometrics Learning Tool. It has some datafiles and
sample control streams. If you can be more specific on what you would
like to understand in the NONMEM output, it would be easier.
Atul
Venkatesh Atul Bhattaram
Pharmacometrics
US Food and Drug Administration
"The contents of this message are mine personally and do not necessarily
reflect any position of the Government or the Food and Drug
Administration."
________________________________
Quoted reply history
From: [EMAIL PROTECTED]
[mailto:[EMAIL PROTECTED] On Behalf Of Tausif Ahmed
Sent: Wednesday, April 11, 2007 6:50 AM
To: [email protected]
Subject: [NMusers] Bayesian estimation example
Dear Group members,
I have recently started using NONMEM for population analysis.
I need you help in understanding Bayesian estimation using
NONMEM.
Can any body provide me a sample control stream along with data
file (Excel or csv format) and also explain the output.
I use Visual NM to run NONMEM version V.
Thanking you in anticipation.
Regards
Tausif Ahmed Ph.D.
Metabolism and Pharmacokinetics Department
Ranbaxy Research Lab
India
(i) The information contained in this e-mail message is intended only
for the confidential use of the recipient(s) named above. This message
is privileged and confidential. If the reader of this message is not the
intended recipient or an agent responsible for delivering it to the
intended recipient, you are hereby notified that you have received this
document in error and that any review, dissemination, distribution, or
copying of this message is strictly prohibited. If you have received
this communication in error, please notify us immediately by e-mail, and
delete the original message.
(ii) The sender confirms that Ranbaxy shall not be responsible if this
email message is used for any indecent, unsolicited or illegal purposes,
which are in violation of any existing laws and the same shall solely be
the responsibility of the sender and that Ranbaxy shall at all times be
indemnified of any civil and/ or criminal liabilities or consequences
there.
Departmental.gif
Description:
Departmental.gif
Hi Tausif,
You are probably talking about two different things. You can obviously get
the emperical bayesian individual esimates using NONMEM. But performing a
Bayesian Estimation is a different approach which utlizes prior information and
current data to generate posterior distribution of the parameter estimates.
There is an excellent pharmacometerics learning tool on www.accp1.org which
provides theory and examples on population analysis and might be very helpful
to you.
Hope this helps
Regards
Nitin
Tausif Ahmed <[EMAIL PROTECTED]> wrote:
Dear Group members,
I have recently started using NONMEM for population analysis.
I need you help in understanding Bayesian estimation using NONMEM.
Can any body provide me a sample control stream along with data file (Excel
or csv format) and also explain the output.
I use Visual NM to run NONMEM version V.
Thanking you in anticipation.
Regards
Tausif Ahmed Ph.D.
Metabolism and Pharmacokinetics Department
Ranbaxy Research Lab
India
(i) The information contained in this e-mail message is intended only
for the confidential use of the recipient(s) named above. This message is
privileged and confidential. If the reader of this message is not the intended
recipient or an agent responsible for delivering it to the intended recipient,
you are hereby notified that you have received this document in error and that
any review, dissemination, distribution, or copying of this message is strictly
prohibited. If you have received this communication in error, please notify us
immediately by e-mail, and delete the original message.
(ii) The sender confirms that Ranbaxy shall not be responsible if this email
message is used for any indecent, unsolicited or illegal purposes, which are in
violation of any existing laws and the same shall solely be the responsibility
of the sender and that Ranbaxy shall at all times be indemnified of any civil
and/ or criminal liabilities or consequences there.
Nitin Mehrotra, Ph.D
Post Doctoral Research Fellow
874 Union Avenue, Suite4.5p/5p
Department of Pharmaceutical Sciences
University of Tennessee Health Science Center
Memphis, TN, USA-38163
901-448-3385 (Lab)
[EMAIL PROTECTED]
---------------------------------
Don't pick lemons.
See all the new 2007 cars at Yahoo! Autos.
Dear Group members,
I will make my objective more clear- I have a drug X in which I have
information in healthy volunteers with extensive sampling done, single
dose (12-14 samples).
I have data on appx. 100 volunteers at different dose levels from phase
I studies.
We also have a data in 16 patients at one dose only, with extensive
sampling.
Now we have data from 200 patients, with 2-3 blood samples collected
from each patient at different doses.
It is also seen that the PK changes in patients.
What I am interested is that can we use Bayesian estimates, (and I think
posthoc estimate from NONMEM, as Yaning mentions) to determine the
pharmacokinetics (PK) of the whole population from these 2-3 blood
samples collected per patient.
Hope it is more clear.
I have checked at website- ( http://www.accp1.org/)as suggested by many
but could not find any control stream on Bayesian. Can the group help me
on this.
I thank the experts for giving their comments on the same.
Regards
Tausif Ahmed Ph.D.
Metabolism and Pharmacokinetics Department
Ranbaxy Research Lab India
Quoted reply history
-----Original Message-----
From: Wang, Yaning [mailto:[EMAIL PROTECTED]
Sent: Wednesday, April 11, 2007 8:30 PM
To: Nick Holford; Tausif Ahmed
Subject: RE: [NMusers] Bayesian estimation example
Nick:
Tausif may be referring to the posthoc estimate from NONMEM (empirical
Bayesian estimate).
Yaning
-----Original Message-----
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]
On Behalf Of Nick Holford
Sent: Wednesday, April 11, 2007 10:43 AM
To: Tausif Ahmed
Cc: [EMAIL PROTECTED]
Subject: Re: [NMusers] Bayesian estimation example
Tausif,
Why do you want to use Bayesian Estimation? If you have only just
started to use NONMEM then perhaps you have misunderstood the reasons
for using it. It is very rarely needed.
Nick
> Dear Group members,
>
> I have recently started using NONMEM for population analysis.
> I need you help in understanding Bayesian estimation using NONMEM.
> Can any body provide me a sample control stream along with data file
(Excel or csv format) and also explain the output.
> I use Visual NM to run NONMEM version V.
>
> Thanking you in anticipation.
>
> Regards
> Tausif Ahmed Ph.D.
> Metabolism and Pharmacokinetics Department Ranbaxy Research Lab India
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology University of
Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
email:[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
(i) The information contained in this e-mail message is intended only for the
confidential use of the recipient(s) named above. This message is privileged
and confidential. If the reader of this message is not the intended recipient
or an agent responsible for delivering it to the intended recipient, you are
hereby notified that you have received this document in error and that any
review, dissemination, distribution, or copying of this message is strictly
prohibited. If you have received this communication in error, please notify us
immediately by e-mail, and delete the original message.
(ii) The sender confirms that Ranbaxy shall not be responsible if this email
message is used for any indecent, unsolicited or illegal purposes, which are in
violation of any existing laws and the same shall solely be the responsibility
of the sender and that Ranbaxy shall at all times be indemnified of any civil
and/ or criminal liabilities or consequences there.
Hello Tausif
One of the many ways to analyze the data you have:
1. Understand the structural model in healthy volunteers using the
average concentration-time data using WinNonlin for example.
2. Use these estimates as your initial parameters and run MAXEVAL=0 in
NONMEM and see how the predictions are (This will give you some idea
about the data from patients and your starting model).
3. You can fix some of the parameters (for example ka) and estimate
the parameters of interest.
If your drug has long half-life and the samples that you have are drawn
at pre-dose, then you can use a simpler model (Css=F*Dose/(CL*Tau)) and
estimate CL.
With data from 200 patients and 2 or 3 samples (depending on when they
were collected), I think you should be able to estimate the parameters
of interest. You don't need any specific control stream for Bayesian
for this purpose. Regular control stream in NONMEM should work for you.
Atul
Venkatesh Atul Bhattaram
Pharmacometrics
US Food and Drug Administration
"The contents of this message are mine personally and do not necessarily
reflect any position of the Government or the Food and Drug
Administration."
Quoted reply history
-----Original Message-----
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]
On Behalf Of Tausif Ahmed
Sent: Thursday, April 12, 2007 7:03 AM
To: [EMAIL PROTECTED]
Subject: RE: [NMusers] Bayesian estimation example
Dear Group members,
I will make my objective more clear- I have a drug X in which I have
information in healthy volunteers with extensive sampling done, single
dose (12-14 samples).
I have data on appx. 100 volunteers at different dose levels from phase
I studies.
We also have a data in 16 patients at one dose only, with extensive
sampling.
Now we have data from 200 patients, with 2-3 blood samples collected
from each patient at different doses.
It is also seen that the PK changes in patients.
What I am interested is that can we use Bayesian estimates, (and I think
posthoc estimate from NONMEM, as Yaning mentions) to determine the
pharmacokinetics (PK) of the whole population from these 2-3 blood
samples collected per patient.
Hope it is more clear.
I have checked at website- ( http://www.accp1.org/)as suggested by many
but could not find any control stream on Bayesian. Can the group help me
on this.
I thank the experts for giving their comments on the same.
Regards
Tausif Ahmed Ph.D.
Metabolism and Pharmacokinetics Department
Ranbaxy Research Lab India
-----Original Message-----
From: Wang, Yaning [mailto:[EMAIL PROTECTED]
Sent: Wednesday, April 11, 2007 8:30 PM
To: Nick Holford; Tausif Ahmed
Subject: RE: [NMusers] Bayesian estimation example
Nick:
Tausif may be referring to the posthoc estimate from NONMEM (empirical
Bayesian estimate).
Yaning
-----Original Message-----
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]
On Behalf Of Nick Holford
Sent: Wednesday, April 11, 2007 10:43 AM
To: Tausif Ahmed
Cc: [EMAIL PROTECTED]
Subject: Re: [NMusers] Bayesian estimation example
Tausif,
Why do you want to use Bayesian Estimation? If you have only just
started to use NONMEM then perhaps you have misunderstood the reasons
for using it. It is very rarely needed.
Nick
> Dear Group members,
>
> I have recently started using NONMEM for population analysis.
> I need you help in understanding Bayesian estimation using NONMEM.
> Can any body provide me a sample control stream along with data file
(Excel or csv format) and also explain the output.
> I use Visual NM to run NONMEM version V.
>
> Thanking you in anticipation.
>
> Regards
> Tausif Ahmed Ph.D.
> Metabolism and Pharmacokinetics Department Ranbaxy Research Lab India
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology University of
Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
email:[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
(i) The information contained in this e-mail message is intended only
for the confidential use of the recipient(s) named above. This message
is privileged and confidential. If the reader of this message is not the
intended recipient or an agent responsible for delivering it to the
intended recipient, you are hereby notified that you have received this
document in error and that any review, dissemination, distribution, or
copying of this message is strictly prohibited. If you have received
this communication in error, please notify us immediately by e-mail, and
delete the original message.
(ii) The sender confirms that Ranbaxy shall not be responsible if this
email message is used for any indecent, unsolicited or illegal purposes,
which are in violation of any existing laws and the same shall solely be
the responsibility of the sender and that Ranbaxy shall at all times be
indemnified of any civil and/ or criminal liabilities or consequences
there.
A standard population PK approach would be appropriate.
Serge Guzy
President, CEO, POP-PHARM
Quoted reply history
-----Original Message-----
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]
On Behalf Of Tausif Ahmed
Sent: Thursday, April 12, 2007 4:03 AM
To: [EMAIL PROTECTED]
Subject: RE: [NMusers] Bayesian estimation example
Dear Group members,
I will make my objective more clear- I have a drug X in which I have
information in healthy volunteers with extensive sampling done, single
dose (12-14 samples).
I have data on appx. 100 volunteers at different dose levels from phase
I studies.
We also have a data in 16 patients at one dose only, with extensive
sampling.
Now we have data from 200 patients, with 2-3 blood samples collected
from each patient at different doses.
It is also seen that the PK changes in patients.
What I am interested is that can we use Bayesian estimates, (and I think
posthoc estimate from NONMEM, as Yaning mentions) to determine the
pharmacokinetics (PK) of the whole population from these 2-3 blood
samples collected per patient.
Hope it is more clear.
I have checked at website- ( http://www.accp1.org/)as suggested by many
but could not find any control stream on Bayesian. Can the group help me
on this.
I thank the experts for giving their comments on the same.
Regards
Tausif Ahmed Ph.D.
Metabolism and Pharmacokinetics Department
Ranbaxy Research Lab India
-----Original Message-----
From: Wang, Yaning [mailto:[EMAIL PROTECTED]
Sent: Wednesday, April 11, 2007 8:30 PM
To: Nick Holford; Tausif Ahmed
Subject: RE: [NMusers] Bayesian estimation example
Nick:
Tausif may be referring to the posthoc estimate from NONMEM (empirical
Bayesian estimate).
Yaning
-----Original Message-----
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]
On Behalf Of Nick Holford
Sent: Wednesday, April 11, 2007 10:43 AM
To: Tausif Ahmed
Cc: [EMAIL PROTECTED]
Subject: Re: [NMusers] Bayesian estimation example
Tausif,
Why do you want to use Bayesian Estimation? If you have only just
started to use NONMEM then perhaps you have misunderstood the reasons
for using it. It is very rarely needed.
Nick
> Dear Group members,
>
> I have recently started using NONMEM for population analysis.
> I need you help in understanding Bayesian estimation using NONMEM.
> Can any body provide me a sample control stream along with data file
(Excel or csv format) and also explain the output.
> I use Visual NM to run NONMEM version V.
>
> Thanking you in anticipation.
>
> Regards
> Tausif Ahmed Ph.D.
> Metabolism and Pharmacokinetics Department Ranbaxy Research Lab India
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology University of
Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
email:[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
(i) The information contained in this e-mail message is intended only
for the confidential use of the recipient(s) named above. This message
is privileged and confidential. If the reader of this message is not the
intended recipient or an agent responsible for delivering it to the
intended recipient, you are hereby notified that you have received this
document in error and that any review, dissemination, distribution, or
copying of this message is strictly prohibited. If you have received
this communication in error, please notify us immediately by e-mail, and
delete the original message.
(ii) The sender confirms that Ranbaxy shall not be responsible if this
email message is used for any indecent, unsolicited or illegal purposes,
which are in violation of any existing laws and the same shall solely be
the responsibility of the sender and that Ranbaxy shall at all times be
indemnified of any civil and/ or criminal liabilities or consequences
there.
--
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Analysis of the data (perform PK analysis on individual subject data & obtaib mean parameters) from initial studies in voulnteers helps in NONMEM analysis of the data from 200 patients. If the data points are widely distributed (entire time range) it is possible to get reasonable estimates of average (pop) values of PK parameters and to study the influence of different covariates. It is advisable to run both FO & FOCE estimations. Plz. read this article: http://www.aapsj.org/view.asp?art=aapsj0901007 in which a survey on different analysis methods (including Bayesian) has been well described by Bauer et al.,
- Best wishes,
Krishna R Devarakonda, PhD
Division of Pharmacology & Clinical Pharmacy,
Kakatiya University,
University College of Pharm. Sci.,
WARANGAL 506 009
----- Original Message ----- From: "Tausif Ahmed" <[EMAIL PROTECTED]>
To: <[EMAIL PROTECTED]>
Sent: Thursday, April 12, 2007 4:33 PM
Subject: RE: [NMusers] Bayesian estimation example
Dear Group members,
I will make my objective more clear- I have a drug X in which I have
information in healthy volunteers with extensive sampling done, single
dose (12-14 samples).
I have data on appx. 100 volunteers at different dose levels from phase
I studies.
We also have a data in 16 patients at one dose only, with extensive
sampling.
Now we have data from 200 patients, with 2-3 blood samples collected
from each patient at different doses.
It is also seen that the PK changes in patients.
What I am interested is that can we use Bayesian estimates, (and I think
posthoc estimate from NONMEM, as Yaning mentions) to determine the
pharmacokinetics (PK) of the whole population from these 2-3 blood
samples collected per patient.
Hope it is more clear.
I have checked at website- ( http://www.accp1.org/)as suggested by many
but could not find any control stream on Bayesian. Can the group help me
on this.
I thank the experts for giving their comments on the same.
Regards
Tausif Ahmed Ph.D.
Metabolism and Pharmacokinetics Department
Ranbaxy Research Lab India
Quoted reply history
-----Original Message-----
From: Wang, Yaning [mailto:[EMAIL PROTECTED]
Sent: Wednesday, April 11, 2007 8:30 PM
To: Nick Holford; Tausif Ahmed
Subject: RE: [NMusers] Bayesian estimation example
Nick:
Tausif may be referring to the posthoc estimate from NONMEM (empirical
Bayesian estimate).
Yaning
-----Original Message-----
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]
On Behalf Of Nick Holford
Sent: Wednesday, April 11, 2007 10:43 AM
To: Tausif Ahmed
Cc: [EMAIL PROTECTED]
Subject: Re: [NMusers] Bayesian estimation example
Tausif,
Why do you want to use Bayesian Estimation? If you have only just
started to use NONMEM then perhaps you have misunderstood the reasons
for using it. It is very rarely needed.
Nick
> Dear Group members,
>
> I have recently started using NONMEM for population analysis.
> I need you help in understanding Bayesian estimation using NONMEM.
> Can any body provide me a sample control stream along with data file
(Excel or csv format) and also explain the output.
> I use Visual NM to run NONMEM version V.
>
> Thanking you in anticipation.
>
> Regards
> Tausif Ahmed Ph.D.
> Metabolism and Pharmacokinetics Department Ranbaxy Research Lab India
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology University of
Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
email:[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
(i) The information contained in this e-mail message is intended only for the confidential use of the recipient(s) named above. This message is privileged and confidential. If the reader of this message is not the intended recipient or an agent responsible for delivering it to the intended recipient, you are hereby notified that you have received this document in error and that any review, dissemination, distribution, or copying of this message is strictly prohibited. If you have received this communication in error, please notify us immediately by e-mail, and delete the original message.
(ii) The sender confirms that Ranbaxy shall not be responsible if this email message is used for any indecent, unsolicited or illegal purposes, which are in violation of any existing laws and the same shall solely be the responsibility of the sender and that Ranbaxy shall at all times be indemnified of any civil and/ or criminal liabilities or consequences there.