date:20151222

RE: [NMusers] Problem of STS in NONMEM

2015-12-22 Thread Mills, Richard

Hi Anyue,

You need to amend MAXEVAL=0 in $EST (I suggest MAXEVAL=) in order to allow 
estimation.

Kind regards,
Richard
Richard Mills PhD
Senior Scientist, PKPDM&S
 [http://emailsignature/stationary/Icon_Development_Solutions.gif]

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From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On 
Behalf Of Anyue Yin
Sent: 22 December 2015 06:36
To: nmusers@globomaxnm.com
Subject: [NMusers] Problem of STS in NONMEM

Dear all,

I got a problem when using NONMEM with STS method. My aim is to get individual 
parameter estimates. I would like to let NONMEM estimate individual parameter 
one subject by one subject. My control stream is partially listed below, which 
is edited according to this thread 
http://www.cognigencorp.com/nonmem/nmo/topic035.html

$SUBROUTINES ADVAN1 TRANS2

$PK
CL = THETA(1) * EXP(ETA(1))
V  = THETA(2) * EXP(ETA(2))
S1 = V

$ERROR
IPRED = F
W = F
Y = IPRED*(1+EXP(ETA(3))*EPS(1))
 IRES = DV-IPRED
IWRES = IRES/W

$THETA
(10,20,30)   ; CL
(10,80,100)  ; V

$OMEGA
100 ; IIV CL
100 ; IIV V
100 ; IIV SIGMA

$SIGMA
1 FIXED ; PRO
$EST METHOD=1 INTER MAXEVAL=0 NOABORT SIG=3 PRINT=1 POSTHOC
$COV
$TABLE ID TIME AMT CMT DV PRED IPRED IWRES CL V ETA(1) ETA(2) ETA(3) ONEHEADER 
NOPRINT FILE=sdtab101.tab

The model can run successfully, and I got individual parameter estimates from 
output file. I found that for each subject the individual parameter estimate 
changed  if I change the initial value of THETA. It seems that NONMEM regarded 
the initial value fixed (just like a fixed typical value). But I expected 
NONMEM to estimate individual parameters based on individual data rather than 
the initial value. Is there anything wrong with the code? Thanks in advance.

Anyue

Re: [NMusers] Problem of STS in NONMEM

2015-12-22 Thread Jeroen Elassaiss-Schaap (PD-value B.V.)

Dear Anyue,

It has been a long time since I used this method. Nowadays NONMEM has
much added functionality, such as the non-parameteric step and the
possibility to repeat problems over individuals in your dataset. My
advise would actually be to use those. The latter especially gives you a
much cleaner implementation of extended least squares if that is what
you are looking for.

Anyway, your code seems fine. Your entries into $THETA and $SIGMA
however do matter. I would suggest to run this once, and than take the
median of parameters and input that into $THETA. Also take the variance
of residuals and put that number into $SIGMA. Now run it again, and the
result should be unbiased. I do not have a reference for this recipe,
please use this at your own discretion.

Hope this helps,
Jeroen

http://pd-value.com
jer...@pd-value.com
@PD_value
+31 6 23118438
-- More value out of your data!

On 12/22/2015 07:36 AM, Anyue Yin wrote:
> Dear all,
>
> I got a problem when using NONMEM with STS method. My aim is to get
> individual parameter estimates. I would like to let NONMEM estimate
> individual parameter one subject by one subject. My control stream is
> partially listed below, which is edited according to this thread
> http://www.cognigencorp.com/nonmem/nmo/topic035.html
>
> /$SUBROUTINES ADVAN1 TRANS2/
> /
> /
> /$PK/
> /CL = THETA(1) * EXP(ETA(1))/
> /V  = THETA(2) * EXP(ETA(2))/
> /S1 = V/
> /
> /
> /$ERROR/
> /IPRED = F/
> /W = F/
> /Y = IPRED*(1+EXP(ETA(3))*EPS(1))/
> / IRES = DV-IPRED/
> /IWRES = IRES/W/
> /
> /
> /$THETA/
> /(10,20,30)   ; CL/
> /(10,80,100)  ; V/
> /
> /
> /$OMEGA/
> /100 ; IIV CL/
> /100 ; IIV V/
> /100 ; IIV SIGMA/
> /
> /
> /$SIGMA/
> /1 FIXED ; PRO/
> /$EST METHOD=1 INTER MAXEVAL=0 NOABORT SIG=3 PRINT=1 POSTHOC/
> /$COV/
> /$TABLE ID TIME AMT CMT DV PRED IPRED IWRES CL V ETA(1) ETA(2) ETA(3)
> ONEHEADER NOPRINT FILE=sdtab101.tab/
>
> The model can run successfully, and I got individual parameter
> estimates from output file. I found that for each subject the
> individual parameter estimate changed  if I change the initial value
> of THETA. It seems that NONMEM regarded the initial value fixed (just
> like a fixed typical value). But I expected NONMEM to estimate
> individual parameters based on individual data rather than the initial
> value. Is there anything wrong with the code? Thanks in advance.
>
> Anyue

RE: [NMusers] Problem of STS in NONMEM

2015-12-22 Thread Mats Karlsson

Dear Anyue,

I don’t know what you mean by “the individual parameter estimate changed  if I 
change the initial value of THETA”

If you mean that individual ETA estimates change, that is expected when you 
change THETA. For CL and V to be the same, ETA need to change when THETA 
change. It may be that you are at local minima for EBEs. You may want to add 
MCETA=1000 on the $EST line in order to test more initial estimates. I would 
use MAXEVAL=0, not MAXEVAL=. Possibly I would use MAXEVAL= after having 
fixed $OMEGA parameters to the high values you use now.

Best regards,
Mats


Mats Karlsson, PhD
Professor of Pharmacometrics

Dept of Pharmaceutical Biosciences
Faculty of Pharmacy
Uppsala University
Box 591
75124 Uppsala

Phone: +46 18 4714105
Fax + 46 18 4714003
www.farmbio.uu.se/research/researchgroups/pharmacometrics/

From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On 
Behalf Of Mills, Richard
Sent: Tuesday, December 22, 2015 8:54 AM
To: Anyue Yin; nmusers@globomaxnm.com
Subject: RE: [NMusers] Problem of STS in NONMEM

Hi Anyue,

You need to amend MAXEVAL=0 in $EST (I suggest MAXEVAL=) in order to allow 
estimation.

Kind regards,
Richard
Richard Mills PhD
Senior Scientist, PKPDM&S
 [http://emailsignature/stationary/Icon_Development_Solutions.gif]

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If you
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distribution, or reliance upon the contents of this e-mail is strictly 
prohibited. If
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ICON plc can arrange for proper delivery, and then please delete the message.
Thank You,
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Ireland
Registered number: 145835



From: owner-nmus...@globomaxnm.com 
[mailto:owner-nmus...@globomaxnm.com] On Behalf Of Anyue Yin
Sent: 22 December 2015 06:36
To: nmusers@globomaxnm.com
Subject: [NMusers] Problem of STS in NONMEM

Dear all,

I got a problem when using NONMEM with STS method. My aim is to get individual 
parameter estimates. I would like to let NONMEM estimate individual parameter 
one subject by one subject. My control stream is partially listed below, which 
is edited according to this thread 
http://www.cognigencorp.com/nonmem/nmo/topic035.html

$SUBROUTINES ADVAN1 TRANS2

$PK
CL = THETA(1) * EXP(ETA(1))
V  = THETA(2) * EXP(ETA(2))
S1 = V

$ERROR
IPRED = F
W = F
Y = IPRED*(1+EXP(ETA(3))*EPS(1))
 IRES = DV-IPRED
IWRES = IRES/W

$THETA
(10,20,30)   ; CL
(10,80,100)  ; V

$OMEGA
100 ; IIV CL
100 ; IIV V
100 ; IIV SIGMA

$SIGMA
1 FIXED ; PRO
$EST METHOD=1 INTER MAXEVAL=0 NOABORT SIG=3 PRINT=1 POSTHOC
$COV
$TABLE ID TIME AMT CMT DV PRED IPRED IWRES CL V ETA(1) ETA(2) ETA(3) ONEHEADER 
NOPRINT FILE=sdtab101.tab

The model can run successfully, and I got individual parameter estimates from 
output file. I found that for each subject the individual parameter estimate 
changed  if I change the initial value of THETA. It seems that NONMEM regarded 
the initial value fixed (just like a fixed typical value). But I expected 
NONMEM to estimate individual parameters based on individual data rather than 
the initial value. Is there anything wrong with the code? Thanks in advance.

Anyue

Re: [NMusers] Problem of STS in NONMEM

2015-12-22 Thread Anyue Yin

Dear all,

Thanks for replying me.

I am trying to carry out the first stage of Standard Two Stage estimation
method in NONMEM (i.e. estimate individual parameter by ID). For the sake
of argument, let's assume that I have a data file which includes 10
subjects (ID from 1 to 10). Now I wish to estimate individual parameter by
fitting each individual data, so I will be able to get 10 individual
parameter estimates. But I found that these 10 individual parameter
estimates were all around the initial value what I assigned to the THETA.
For example, if I assign 20 to the initial value of THETA, then these 10
parameter estimates are all around 20. If I assign 30, then all around
30... It looks like NONMEM uses initial value of THETA as prior to estimate
individual parameters. What I expect is to estimate individual parameters
by ID, as if these 10 subjects are separated into 10 data file and estimate
10 times to get each result. So the key point of my question is individual
parameter estimation by the first stage of STS in NONMEM. Thank you very
much.

Sincerely,
Anyue

On Tue, Dec 22, 2015 at 5:33 PM, Mats Karlsson 
wrote:

> Dear Anyue,
>
>
>
> I don’t know what you mean by “the individual parameter estimate changed
>  if I change the initial value of THETA”
>
>
>
> If you mean that individual ETA estimates change, that is expected when
> you change THETA. For CL and V to be the same, ETA need to change when
> THETA change. It may be that you are at local minima for EBEs. You may want
> to add MCETA=1000 on the $EST line in order to test more initial estimates.
> I would use MAXEVAL=0, not MAXEVAL=. Possibly I would use MAXEVAL=
> after having fixed $OMEGA parameters to the high values you use now.
>
>
>
> Best regards,
>
> Mats
>
>
>
>
>
> Mats Karlsson, PhD
>
> Professor of Pharmacometrics
>
>
>
> Dept of Pharmaceutical Biosciences
>
> Faculty of Pharmacy
>
> Uppsala University
>
> Box 591
>
> 75124 Uppsala
>
>
>
> Phone: +46 18 4714105
>
> Fax + 46 18 4714003
>
> www.farmbio.uu.se/research/researchgroups/pharmacometrics/
>
>
>
> *From:* owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com]
> *On Behalf Of *Mills, Richard
> *Sent:* Tuesday, December 22, 2015 8:54 AM
> *To:* Anyue Yin; nmusers@globomaxnm.com
> *Subject:* RE: [NMusers] Problem of STS in NONMEM
>
>
>
> Hi Anyue,
>
>
>
> You need to amend MAXEVAL=0 in $EST (I suggest MAXEVAL=) in order to
> allow estimation.
>
>
>
> Kind regards,
>
> Richard
>
>
> *Richard Mills PhD Senior Scientist, PKPDM&S*
>
>  [image: http://emailsignature/stationary/Icon_Development_Solutions.gif]
>
>
>
> ICON plc made the following annotations.
>
>
> --
>
> This e-mail transmission may contain confidential or legally privileged
> information
>
> that is intended only for the individual or entity named in the e-mail
> address. If you
>
> are not the intended recipient, you are hereby notified that any
> disclosure, copying,
>
> distribution, or reliance upon the contents of this e-mail is strictly
> prohibited. If
>
> you have received this e-mail transmission in error, please reply to the
> sender, so that
>
> ICON plc can arrange for proper delivery, and then please delete the
> message.
>
> Thank You,
>
> ICON plc
>
> South County Business Park
>
> Leopardstown
>
> Dublin 18
>
> Ireland
>
> Registered number: 145835
>
>
>
>
>
>
>
> *From:* owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com
> ] *On Behalf Of *Anyue Yin
> *Sent:* 22 December 2015 06:36
> *To:* nmusers@globomaxnm.com
> *Subject:* [NMusers] Problem of STS in NONMEM
>
>
>
> Dear all,
>
>
>
> I got a problem when using NONMEM with STS method. My aim is to get
> individual parameter estimates. I would like to let NONMEM estimate
> individual parameter one subject by one subject. My control stream is
> partially listed below, which is edited according to this thread
> http://www.cognigencorp.com/nonmem/nmo/topic035.html
>
>
>
> *$SUBROUTINES ADVAN1 TRANS2*
>
>
>
> *$PK*
>
> *CL = THETA(1) * EXP(ETA(1))*
>
> *V  = THETA(2) * EXP(ETA(2))*
>
> *S1 = V*
>
>
>
> *$ERROR*
>
> *IPRED = F*
>
> *W = F*
>
> *Y = IPRED*(1+EXP(ETA(3))*EPS(1))*
>
> * IRES = DV-IPRED*
>
> *IWRES = IRES/W*
>
>
>
> *$THETA*
>
> *(10,20,30)   ; CL*
>
> *(10,80,100)  ; V*
>
>
>
> *$OMEGA*
>
> *100 ; IIV CL*
>
> *100 ; IIV V*
>
> *100 ; IIV SIGMA*
>
>
>
> *$SIGMA*
>
> *1 FIXED ; PRO*
>
> *$EST METHOD=1 INTER MAXEVAL=0 NOABORT SIG=3 PRINT=1 POSTHOC*
>
> *$COV*
>
> *$TABLE ID TIME AMT CMT DV PRED IPRED IWRES CL V ETA(1) ETA(2) ETA(3)
> ONEHEADER NOPRINT FILE=sdtab101.tab*
>
>
>
> The model can run successfully, and I got individual parameter estimates
> from output file. I found that for each subject the individual parameter
> estimate changed  if I change the initial value of THETA. It seems that
> NONMEM regarded the initial value fixed (just like a fixed typical value).
> But I expected NONMEM to estimate individual paramete

RE: [NMusers] Problem of STS in NONMEM

2015-12-22 Thread Standing Joseph (GREAT ORMOND STREET HOSPITAL FOR CHILDREN NHS FOUNDATION TRUST)

Dear Anyue,

I think you are trying to make a short-cut to getting individual parameter 
estimates in one go.  It maybe possible for someone more intelligent than me, 
but can I suggest just doing it the long way round by fitting the model to each 
individual in turn.  Something like this should work if you use R:

two.st.par <- NULL
for(i in c(1:10)){
  all.data <- read.csv("ALLDATA.csv",h=T)
  one.data <- all.data[all.data$ID==i,]
  write.csv(one.data,"i.data.csv",row.names=F,quote=F) # set $DATA i.data.csv 
in your control stream
  # Summons NONMEM - I think in windows you might use shell rather than system?
  system("nmfe73 run1.mod run1.lst",wait=TRUE) # Set $OMEGA 0 FIX in your model 
file, estimate residual with e.g. $SIGMA 0.1
  param.out <- read.table("run1.ext",skip=1,h=T)
  param.out <- param.out[param.out$ITERATION==-10,]
  param.out <- c(param.out$THETA1,param.out$THETA2)
  two.st.par <- rbind(two.st.par,param.out)
}


then two.st.par contains individual parameter ests for each individual.

Best wishes,

Joe


Joseph F Standing
MRC Fellow, UCL Institute of Child Health
Antimicrobial Pharmacist, Great Ormond Street Hospital
Tel: +44(0)207 905 2370
Mobile: +44(0)7970 572435

From: owner-nmus...@globomaxnm.com [owner-nmus...@globomaxnm.com] On Behalf Of 
Anyue Yin [anyueyin...@gmail.com]
Sent: 22 December 2015 10:32
To: Mats Karlsson; Mills, Richard; Jeroen Elassaiss-Schaap (PD-value B.V.); 
r.terhe...@radboudumc.nl
Cc: nmusers@globomaxnm.com
Subject: Re: [NMusers] Problem of STS in NONMEM

Dear all,

Thanks for replying me.

I am trying to carry out the first stage of Standard Two Stage estimation 
method in NONMEM (i.e. estimate individual parameter by ID). For the sake of 
argument, let's assume that I have a data file which includes 10 subjects (ID 
from 1 to 10). Now I wish to estimate individual parameter by fitting each 
individual data, so I will be able to get 10 individual parameter estimates. 
But I found that these 10 individual parameter estimates were all around the 
initial value what I assigned to the THETA. For example, if I assign 20 to the 
initial value of THETA, then these 10 parameter estimates are all around 20. If 
I assign 30, then all around 30... It looks like NONMEM uses initial value of 
THETA as prior to estimate individual parameters. What I expect is to estimate 
individual parameters by ID, as if these 10 subjects are separated into 10 data 
file and estimate 10 times to get each result. So the key point of my question 
is individual parameter estimation by the first stage of STS in NONMEM. Thank 
you very much.

Sincerely,
Anyue

On Tue, Dec 22, 2015 at 5:33 PM, Mats Karlsson 
mailto:mats.karls...@farmbio.uu.se>> wrote:
Dear Anyue,

I don’t know what you mean by “the individual parameter estimate changed  if I 
change the initial value of THETA”

If you mean that individual ETA estimates change, that is expected when you 
change THETA. For CL and V to be the same, ETA need to change when THETA 
change. It may be that you are at local minima for EBEs. You may want to add 
MCETA=1000 on the $EST line in order to test more initial estimates. I would 
use MAXEVAL=0, not MAXEVAL=. Possibly I would use MAXEVAL= after having 
fixed $OMEGA parameters to the high values you use now.

Best regards,
Mats


Mats Karlsson, PhD
Professor of Pharmacometrics

Dept of Pharmaceutical Biosciences
Faculty of Pharmacy
Uppsala University
Box 591
75124 Uppsala

Phone: +46 18 4714105
Fax + 46 18 4714003
www.farmbio.uu.se/research/researchgroups/pharmacometrics/

From: owner-nmus...@globomaxnm.com 
[mailto:owner-nmus...@globomaxnm.com] On 
Behalf Of Mills, Richard
Sent: Tuesday, December 22, 2015 8:54 AM
To: Anyue Yin; nmusers@globomaxnm.com
Subject: RE: [NMusers] Problem of STS in NONMEM

Hi Anyue,

You need to amend MAXEVAL=0 in $EST (I suggest MAXEVAL=) in order to allow 
estimation.

Kind regards,
Richard
Richard Mills PhD
Senior Scientist, PKPDM&S
 [cid:image001.jpg@01D13CA4.38DCE9C0]

ICON plc made the following annotations.
--
This e-mail transmission may contain confidential or legally privileged 
information
that is intended only for the individual or entity named in the e-mail address. 
If you
are not the intended recipient, you are hereby notified that any disclosure, 
copying,
distribution, or reliance upon the contents of this e-mail is strictly 
prohibited. If
you have received this e-mail transmission in error, please reply to the 
sender, so that
ICON plc can arrange for proper delivery, and then please delete the message.
Thank You,
ICON plc
South County Business Park
Leopardstown
Dublin 18
Ireland
Registered number: 145835



From: owner-nmus...@globomaxnm.com

[NMusers] Nested if

2015-12-22 Thread Andre Jackson

All:

 

I have a control stream that runs okay which involves differential
equations.  When I requested an output table containing thetas I  got this
error.

, " The characters in error are: Theta  479 This item is not listed in
module NMPRD4 and may not be displayed."

 

I have searched the archives and came across a post from 2011 which
discussed the relationship of PREDPP to this module NMPRD4.

Part of the post stated, "Every variable displayed via $TABLE has the value
that was calculated by the last call to DES with the current event record.
This is not a design  decision; it is inevitable. Values created by PREDPP
for display by NONMEM are stored in a common area (formerly COMMON NMPRD4;
now MODULE NMPRD4)."

 

However there was insufficient discussion for me to figure out how to
resolve this issue.   I would be very appreciative if someone with
experience with this problem could advise me how it can be corrected so that
I can generate a table containing my final Theta and Eta values from Nonmem
73?

 

 

Thanks,

Andre

 

Andre Jackson

jacksonan1...@gmail.com

Re: [NMusers] Problem of STS in NONMEM

2015-12-22 Thread Leonid Gibiansky

You may try to remove eta3. As you set it now, you allow very large residual 
error, and nonmem returns initial estimates as final
Leonid



> On Dec 22, 2015, at 5:32 AM, Anyue Yin  wrote:
> 
> Dear all,
> 
> Thanks for replying me.
> 
> I am trying to carry out the first stage of Standard Two Stage estimation 
> method in NONMEM (i.e. estimate individual parameter by ID). For the sake of 
> argument, let's assume that I have a data file which includes 10 subjects (ID 
> from 1 to 10). Now I wish to estimate individual parameter by fitting each 
> individual data, so I will be able to get 10 individual parameter estimates. 
> But I found that these 10 individual parameter estimates were all around the 
> initial value what I assigned to the THETA. For example, if I assign 20 to 
> the initial value of THETA, then these 10 parameter estimates are all around 
> 20. If I assign 30, then all around 30... It looks like NONMEM uses initial 
> value of THETA as prior to estimate individual parameters. What I expect is 
> to estimate individual parameters by ID, as if these 10 subjects are 
> separated into 10 data file and estimate 10 times to get each result. So the 
> key point of my question is individual parameter estimation by the first 
> stage of STS in NONMEM. Thank you very much.
> 
> Sincerely,
> Anyue
> 
>> On Tue, Dec 22, 2015 at 5:33 PM, Mats Karlsson  
>> wrote:
>> Dear Anyue,
>> 
>>  
>> 
>> I don’t know what you mean by “the individual parameter estimate changed  if 
>> I change the initial value of THETA”
>> 
>>  
>> 
>> If you mean that individual ETA estimates change, that is expected when you 
>> change THETA. For CL and V to be the same, ETA need to change when THETA 
>> change. It may be that you are at local minima for EBEs. You may want to add 
>> MCETA=1000 on the $EST line in order to test more initial estimates. I would 
>> use MAXEVAL=0, not MAXEVAL=. Possibly I would use MAXEVAL= after 
>> having fixed $OMEGA parameters to the high values you use now.
>> 
>>  
>> 
>> Best regards,
>> 
>> Mats
>> 
>>  
>> 
>>  
>> 
>> Mats Karlsson, PhD
>> 
>> Professor of Pharmacometrics
>> 
>>  
>> 
>> Dept of Pharmaceutical Biosciences
>> 
>> Faculty of Pharmacy
>> 
>> Uppsala University
>> 
>> Box 591
>> 
>> 75124 Uppsala
>> 
>>  
>> 
>> Phone: +46 18 4714105
>> 
>> Fax + 46 18 4714003
>> 
>> www.farmbio.uu.se/research/researchgroups/pharmacometrics/
>> 
>>  
>> 
>> From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On 
>> Behalf Of Mills, Richard
>> Sent: Tuesday, December 22, 2015 8:54 AM
>> To: Anyue Yin; nmusers@globomaxnm.com
>> Subject: RE: [NMusers] Problem of STS in NONMEM
>> 
>>  
>> 
>> Hi Anyue,
>> 
>>  
>> 
>> You need to amend MAXEVAL=0 in $EST (I suggest MAXEVAL=) in order to 
>> allow estimation.
>> 
>>  
>> 
>> Kind regards,
>> 
>> Richard
>> 
>> Richard Mills PhD
>> Senior Scientist, PKPDM&S
>> 
>>  
>> 
>>  
>> 
>> ICON plc made the following annotations.
>> 
>> --
>> 
>> This e-mail transmission may contain confidential or legally privileged 
>> information
>> 
>> that is intended only for the individual or entity named in the e-mail 
>> address. If you
>> 
>> are not the intended recipient, you are hereby notified that any disclosure, 
>> copying,
>> 
>> distribution, or reliance upon the contents of this e-mail is strictly 
>> prohibited. If
>> 
>> you have received this e-mail transmission in error, please reply to the 
>> sender, so that
>> 
>> ICON plc can arrange for proper delivery, and then please delete the message.
>> 
>> Thank You,
>> 
>> ICON plc
>> 
>> South County Business Park
>> 
>> Leopardstown
>> 
>> Dublin 18
>> 
>> Ireland
>> 
>> Registered number: 145835
>> 
>>  
>> 
>>  
>> 
>>  
>> 
>> From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On 
>> Behalf Of Anyue Yin
>> Sent: 22 December 2015 06:36
>> To: nmusers@globomaxnm.com
>> Subject: [NMusers] Problem of STS in NONMEM
>> 
>>  
>> 
>> Dear all,
>> 
>>  
>> 
>> I got a problem when using NONMEM with STS method. My aim is to get 
>> individual parameter estimates. I would like to let NONMEM estimate 
>> individual parameter one subject by one subject. My control stream is 
>> partially listed below, which is edited according to this thread 
>> http://www.cognigencorp.com/nonmem/nmo/topic035.html
>> 
>>  
>> 
>> $SUBROUTINES ADVAN1 TRANS2
>> 
>>  
>> 
>> $PK
>> 
>> CL = THETA(1) * EXP(ETA(1))
>> 
>> V  = THETA(2) * EXP(ETA(2))
>> 
>> S1 = V
>> 
>>  
>> 
>> $ERROR
>> 
>> IPRED = F
>> 
>> W = F
>> 
>> Y = IPRED*(1+EXP(ETA(3))*EPS(1))
>> 
>>  IRES = DV-IPRED
>> 
>> IWRES = IRES/W
>> 
>>  
>> 
>> $THETA
>> 
>> (10,20,30)   ; CL
>> 
>> (10,80,100)  ; V
>> 
>>  
>> 
>> $OMEGA
>> 
>> 100 ; IIV CL
>> 
>> 100 ; IIV V
>> 
>> 100 ; IIV SIGMA
>> 
>>  
>> 
>> $SIGMA
>> 
>> 1 FIXED ; PRO
>> 
>> $EST METHOD=1 INTER MAXEVAL=0 NOABORT SIG=3 PRINT=1 POSTHOC
>> 
>> $COV
>> 
>> $TABLE ID TIM

[NMusers] BAYES method and initial estimate bounds

2015-12-22 Thread Bill Gillespie

Hi all,

If bounds are specified in the $THETA statements for initial estimates,
what, if any, effect do they have when the BAYES method is used?

I initially thought they might work in conjunction with the prior
specifications to implement truncated priors. However that does not seem to
be true because statements like "IF(ABS(THETA(1)) > 10) EXIT 1 14"
sometimes get tripped even when THETA(1) is  bounded between -10 and 10 in
the $THETA statement.

Happy Holidays,
Bill

RE: [NMusers] BAYES method and initial estimate bounds

2015-12-22 Thread Bauer, Robert

Bill:
I just tested this on a simple script (see below), and the boundaries are 
imposed in BAYES analysis for me.

$PROB RUN# Example 1 (from samp5l)
$INPUT C SET ID JID TIME  DV=CONC AMT=DOSE RATE EVID MDV CMT CLX V1X QX V2X 
SDIX SDSX
$DATA example1.csv IGNORE=C
$SUBROUTINES ADVAN3 TRANS4
$PK
MU_1=THETA(1)
MU_2=THETA(2)
MU_3=THETA(3)
MU_4=THETA(4)
IF (THETA(1)<1.63.OR.THETA(1)>1.8) WRITE(50,*) THETA(1)
CL=DEXP(THETA(1)+ETA(1))
V1=DEXP(THETA(2)+ETA(2))
Q=DEXP(MU_3+ETA(3))
V2=DEXP(MU_4+ETA(4))
S1=V1
$ERROR
Y = F + F*EPS(1)
$THETA (1.63, 1.67,1.8) 2.0 2.0 2.0
$OMEGA BLOCK(4) VALUES(0.15,0.01)
$SIGMA  (0.6 )
$PRIOR NWPRI
$THETAP (2.0 FIX) (2.0 FIX) (2.0 FIX) (2.0 FIX)
$THETAPV BLOCK(4) FIX VALUES(1,0.0)
$OMEGAP BLOCK(4) FIX VALUES(0.2,0.0)
$OMEGAPD (4 FIX)
$EST METHOD=BAYES INTERACTION NITER=1000 PRINT=100 CTYPE=3
$COV MATRIX=R PRINT=E UNCONDITIONAL

Robert J. Bauer, Ph.D.
Vice President, Pharmacometrics R&D
ICON Early Phase
Office: (215) 616-6428
Mobile: (925) 286-0769
robert.ba...@iconplc.com
www.iconplc.com

From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On 
Behalf Of Bill Gillespie
Sent: Tuesday, December 22, 2015 8:14 AM
To: nmusers@globomaxnm.com
Subject: [NMusers] BAYES method and initial estimate bounds

Hi all,

If bounds are specified in the $THETA statements for initial estimates, what, 
if any, effect do they have when the BAYES method is used?

I initially thought they might work in conjunction with the prior 
specifications to implement truncated priors. However that does not seem to be 
true because statements like "IF(ABS(THETA(1)) > 10) EXIT 1 14" sometimes get 
tripped even when THETA(1) is  bounded between -10 and 10 in the $THETA 
statement.

Happy Holidays,
Bill

ICON plc made the following annotations.
--
This e-mail transmission may contain confidential or legally privileged 
information that is intended only for the individual or entity named in the 
e-mail address. If you
are not the intended recipient, you are hereby notified that any disclosure, 
copying, distribution, or reliance upon the contents of this e-mail is strictly 
prohibited. If
you have received this e-mail transmission in error, please reply to the 
sender, so that ICON plc can arrange for proper delivery, and then please 
delete the message.

Thank You,

ICON plc
South County Business Park
Leopardstown
Dublin 18
Ireland
Registered number: 145835

[NMusers] Mark Your Calendars! Hold the Dates! ICON NONMEM/PDxPoP Workshops for 2016

2015-12-22 Thread Wilhelm-Lear, Lisa

The following workshops have been scheduled for 2016:

March 1-3 – San Francisco, California – 3-day NONMEM/PDxPoP Workshop
Location:  Doubletree by Hilton San Francisco Airport, 835 Airport Boulevard, 
Burlingame, CA  94010 (just 10 minutes from the airport!)

March 4 – San Francisco, California – TMDD Workshop presented by Leonid and 
Ekaterina Gibiansky of QuantPharm LLC
Location:  Doubletree by Hilton San Francisco Airport, 835 Airport Boulevard, 
Burlingame, CA  94010 (just 10 minutes from the airport!)

April 12-14 – Howard County Maryland – 3-day NONMEM/PDxPoP Workshop

September 13-15 – Howard County Maryland – 3-day NONMEM/PDxPoP Workshop

All of the workshops above have the following fees associated:

$800 per day per person – Industry
$700 per day per person – Academia
$600 per day per person – Student

==

June 5 – 1 Day Advanced Methods NONMEM workshop – PAGE 2016 – Lisbon, Portugal

$500 per person – industry
$250 per person - academia
$100 per person - student

October 22 – 1 Day Advanced Methods NONMEM Workshop – ACoP 2016 – Seattle, 
Washington

$600 per person – industry
$300 per person – academia
$150 per person – student

The workshops are not yet on our website for registration but if you are 
interested in any of the dates listed or have questions about the workshops, 
please contact me at:  lisa.wilh...@iconplc.com

Kind regards,



Lisa R. Wilhelm-Lear
Customer Service Lead
NONMEM / PDxPoP Software

Phone:  301-944-6771
Fax: 215-789-9549
www.iconplc.com




ICON plc made the following annotations.
--
This e-mail transmission may contain confidential or legally privileged 
information that is intended only for the individual or entity named in the 
e-mail address. If you are not the intended recipient, you are hereby notified 
that any disclosure, copying, distribution, or reliance upon the contents of 
this e-mail is strictly prohibited. If you have received this e-mail 
transmission in error, please reply to the sender, so that ICON plc can arrange 
for proper delivery, and then please delete the message.

Thank You,

ICON plc
South County Business Park
Leopardstown
Dublin 18
Ireland
Registered number: 145835

Re: [NMusers] BAYES method and initial estimate bounds

2015-12-22 Thread Bill Gillespie

Hi Bob,

Thanks for the reply. On investigating further I see this happens when
NONMEM reports a THETA value of 1.34+154 in the PRDERR file. Would I be
correct in thinking that is the result of a floating point error somewhere
in the sampling process?

Thanks,
Bill

On Tue, Dec 22, 2015 at 12:40 PM, Bauer, Robert 
wrote:

> Bill:
>
> I just tested this on a simple script (see below), and the boundaries are
> imposed in BAYES analysis for me.
>
>
>
> $PROB RUN# Example 1 (from samp5l)
>
> $INPUT C SET ID JID TIME  DV=CONC AMT=DOSE RATE EVID MDV CMT CLX V1X QX
> V2X SDIX SDSX
>
> $DATA example1.csv IGNORE=C
>
> $SUBROUTINES ADVAN3 TRANS4
>
> $PK
>
> MU_1=THETA(1)
>
> MU_2=THETA(2)
>
> MU_3=THETA(3)
>
> MU_4=THETA(4)
>
> IF (THETA(1)<1.63.OR.THETA(1)>1.8) WRITE(50,*) THETA(1)
>
> CL=DEXP(THETA(1)+ETA(1))
>
> V1=DEXP(THETA(2)+ETA(2))
>
> Q=DEXP(MU_3+ETA(3))
>
> V2=DEXP(MU_4+ETA(4))
>
> S1=V1
>
> $ERROR
>
> Y = F + F*EPS(1)
>
> $THETA (1.63, 1.67,1.8) 2.0 2.0 2.0
>
> $OMEGA BLOCK(4) VALUES(0.15,0.01)
>
> $SIGMA  (0.6 )
>
> $PRIOR NWPRI
>
> $THETAP (2.0 FIX) (2.0 FIX) (2.0 FIX) (2.0 FIX)
>
> $THETAPV BLOCK(4) FIX VALUES(1,0.0)
>
> $OMEGAP BLOCK(4) FIX VALUES(0.2,0.0)
>
> $OMEGAPD (4 FIX)
>
> $EST METHOD=BAYES INTERACTION NITER=1000 PRINT=100 CTYPE=3
>
> $COV MATRIX=R PRINT=E UNCONDITIONAL
>
>
>
> Robert J. Bauer, Ph.D.
>
> Vice President, Pharmacometrics R&D
>
> ICON Early Phase
>
> Office: (215) 616-6428
>
> Mobile: (925) 286-0769
>
> robert.ba...@iconplc.com
>
> www.iconplc.com
>
>
>
> *From:* owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com]
> *On Behalf Of *Bill Gillespie
> *Sent:* Tuesday, December 22, 2015 8:14 AM
> *To:* nmusers@globomaxnm.com
> *Subject:* [NMusers] BAYES method and initial estimate bounds
>
>
>
> Hi all,
>
>
>
> If bounds are specified in the $THETA statements for initial estimates,
> what, if any, effect do they have when the BAYES method is used?
>
>
>
> I initially thought they might work in conjunction with the prior
> specifications to implement truncated priors. However that does not seem to
> be true because statements like "IF(ABS(THETA(1)) > 10) EXIT 1 14"
> sometimes get tripped even when THETA(1) is  bounded between -10 and 10 in
> the $THETA statement.
>
>
>
> Happy Holidays,
>
> Bill
>
>
> ICON plc made the following annotations.
> --
>
> This e-mail transmission may contain confidential or legally privileged
> information that is intended only for the individual or entity named in the
> e-mail address. If you are not the intended recipient, you are hereby
> notified that any disclosure, copying, distribution, or reliance upon the
> contents of this e-mail is strictly prohibited. If you have received this
> e-mail transmission in error, please reply to the sender, so that ICON plc
> can arrange for proper delivery, and then please delete the message.
>
> Thank You,
>
> ICON plc
> South County Business Park
> Leopardstown
> Dublin 18
> Ireland
> Registered number: 145835
>
>

RE: [NMusers] BAYES method and initial estimate bounds

2015-12-22 Thread Bauer, Robert

Bill:
Yes, and when that happens, the execution path is difficult to anticipate.

Robert J. Bauer, Ph.D.
Vice President, Pharmacometrics R&D
ICON Early Phase
Office: (215) 616-6428
Mobile: (925) 286-0769
robert.ba...@iconplc.com
www.iconplc.com

From: Bill Gillespie [mailto:bgillespies...@gmail.com]
Sent: Tuesday, December 22, 2015 11:25 AM
To: Bauer, Robert
Cc: nmusers@globomaxnm.com
Subject: Re: [NMusers] BAYES method and initial estimate bounds

Hi Bob,

Thanks for the reply. On investigating further I see this happens when NONMEM 
reports a THETA value of 1.34+154 in the PRDERR file. Would I be correct in 
thinking that is the result of a floating point error somewhere in the sampling 
process?

Thanks,
Bill

On Tue, Dec 22, 2015 at 12:40 PM, Bauer, Robert 
mailto:robert.ba...@iconplc.com>> wrote:
Bill:
I just tested this on a simple script (see below), and the boundaries are 
imposed in BAYES analysis for me.

$PROB RUN# Example 1 (from samp5l)
$INPUT C SET ID JID TIME  DV=CONC AMT=DOSE RATE EVID MDV CMT CLX V1X QX V2X 
SDIX SDSX
$DATA example1.csv IGNORE=C
$SUBROUTINES ADVAN3 TRANS4
$PK
MU_1=THETA(1)
MU_2=THETA(2)
MU_3=THETA(3)
MU_4=THETA(4)
IF (THETA(1)<1.63.OR.THETA(1)>1.8) WRITE(50,*) THETA(1)
CL=DEXP(THETA(1)+ETA(1))
V1=DEXP(THETA(2)+ETA(2))
Q=DEXP(MU_3+ETA(3))
V2=DEXP(MU_4+ETA(4))
S1=V1
$ERROR
Y = F + F*EPS(1)
$THETA (1.63, 1.67,1.8) 2.0 2.0 2.0
$OMEGA BLOCK(4) VALUES(0.15,0.01)
$SIGMA  (0.6 )
$PRIOR NWPRI
$THETAP (2.0 FIX) (2.0 FIX) (2.0 FIX) (2.0 FIX)
$THETAPV BLOCK(4) FIX VALUES(1,0.0)
$OMEGAP BLOCK(4) FIX VALUES(0.2,0.0)
$OMEGAPD (4 FIX)
$EST METHOD=BAYES INTERACTION NITER=1000 PRINT=100 CTYPE=3
$COV MATRIX=R PRINT=E UNCONDITIONAL

Robert J. Bauer, Ph.D.
Vice President, Pharmacometrics R&D
ICON Early Phase
Office: (215) 616-6428
Mobile: (925) 286-0769
robert.ba...@iconplc.com
www.iconplc.com

From: owner-nmus...@globomaxnm.com 
[mailto:owner-nmus...@globomaxnm.com] On 
Behalf Of Bill Gillespie
Sent: Tuesday, December 22, 2015 8:14 AM
To: nmusers@globomaxnm.com
Subject: [NMusers] BAYES method and initial estimate bounds

Hi all,

If bounds are specified in the $THETA statements for initial estimates, what, 
if any, effect do they have when the BAYES method is used?

I initially thought they might work in conjunction with the prior 
specifications to implement truncated priors. However that does not seem to be 
true because statements like "IF(ABS(THETA(1)) > 10) EXIT 1 14" sometimes get 
tripped even when THETA(1) is  bounded between -10 and 10 in the $THETA 
statement.

Happy Holidays,
Bill


ICON plc made the following annotations.
--
This e-mail transmission may contain confidential or legally privileged 
information that is intended only for the individual or entity named in the 
e-mail address. If you are not the intended recipient, you are hereby notified 
that any disclosure, copying, distribution, or reliance upon the contents of 
this e-mail is strictly prohibited. If you have received this e-mail 
transmission in error, please reply to the sender, so that ICON plc can arrange 
for proper delivery, and then please delete the message.

Thank You,

ICON plc
South County Business Park
Leopardstown
Dublin 18
Ireland
Registered number: 145835

RE: [NMusers] BAYES method and initial estimate bounds

2015-12-22 Thread Bob Leary

1.34+154 is often on many systems used to indicate an improbably large floating 
point number that is likely an error of some sort. It is the sqrt of the 
largest representable real*8 value, 1.797+308

From: owner-nmus...@globomaxnm.com [owner-nmus...@globomaxnm.com] on behalf of 
Bauer, Robert [robert.ba...@iconplc.com]
Sent: Tuesday, December 22, 2015 1:40 PM
To: Bill Gillespie
Cc: nmusers@globomaxnm.com
Subject: RE: [NMusers] BAYES method and initial estimate bounds

Bill:
Yes, and when that happens, the execution path is difficult to anticipate.

Robert J. Bauer, Ph.D.
Vice President, Pharmacometrics R&D
ICON Early Phase
Office: (215) 616-6428
Mobile: (925) 286-0769
robert.ba...@iconplc.com
www.iconplc.com

From: Bill Gillespie [mailto:bgillespies...@gmail.com]
Sent: Tuesday, December 22, 2015 11:25 AM
To: Bauer, Robert
Cc: nmusers@globomaxnm.com
Subject: Re: [NMusers] BAYES method and initial estimate bounds

Hi Bob,

Thanks for the reply. On investigating further I see this happens when NONMEM 
reports a THETA value of 1.34+154 in the PRDERR file. Would I be correct in 
thinking that is the result of a floating point error somewhere in the sampling 
process?

Thanks,
Bill

On Tue, Dec 22, 2015 at 12:40 PM, Bauer, Robert 
mailto:robert.ba...@iconplc.com>> wrote:
Bill:
I just tested this on a simple script (see below), and the boundaries are 
imposed in BAYES analysis for me.

$PROB RUN# Example 1 (from samp5l)
$INPUT C SET ID JID TIME  DV=CONC AMT=DOSE RATE EVID MDV CMT CLX V1X QX V2X 
SDIX SDSX
$DATA example1.csv IGNORE=C
$SUBROUTINES ADVAN3 TRANS4
$PK
MU_1=THETA(1)
MU_2=THETA(2)
MU_3=THETA(3)
MU_4=THETA(4)
IF (THETA(1)<1.63.OR.THETA(1)>1.8) WRITE(50,*) THETA(1)
CL=DEXP(THETA(1)+ETA(1))
V1=DEXP(THETA(2)+ETA(2))
Q=DEXP(MU_3+ETA(3))
V2=DEXP(MU_4+ETA(4))
S1=V1
$ERROR
Y = F + F*EPS(1)
$THETA (1.63, 1.67,1.8) 2.0 2.0 2.0
$OMEGA BLOCK(4) VALUES(0.15,0.01)
$SIGMA  (0.6 )
$PRIOR NWPRI
$THETAP (2.0 FIX) (2.0 FIX) (2.0 FIX) (2.0 FIX)
$THETAPV BLOCK(4) FIX VALUES(1,0.0)
$OMEGAP BLOCK(4) FIX VALUES(0.2,0.0)
$OMEGAPD (4 FIX)
$EST METHOD=BAYES INTERACTION NITER=1000 PRINT=100 CTYPE=3
$COV MATRIX=R PRINT=E UNCONDITIONAL

Robert J. Bauer, Ph.D.
Vice President, Pharmacometrics R&D
ICON Early Phase
Office: (215) 616-6428
Mobile: (925) 286-0769
robert.ba...@iconplc.com
www.iconplc.com

From: owner-nmus...@globomaxnm.com 
[mailto:owner-nmus...@globomaxnm.com] On 
Behalf Of Bill Gillespie
Sent: Tuesday, December 22, 2015 8:14 AM
To: nmusers@globomaxnm.com
Subject: [NMusers] BAYES method and initial estimate bounds

Hi all,

If bounds are specified in the $THETA statements for initial estimates, what, 
if any, effect do they have when the BAYES method is used?

I initially thought they might work in conjunction with the prior 
specifications to implement truncated priors. However that does not seem to be 
true because statements like "IF(ABS(THETA(1)) > 10) EXIT 1 14" sometimes get 
tripped even when THETA(1) is  bounded between -10 and 10 in the $THETA 
statement.

Happy Holidays,
Bill

ICON plc made the following annotations.
--
This e-mail transmission may contain confidential or legally privileged 
information that is intended only for the individual or entity named in the 
e-mail address. If you are not the intended recipient, you are hereby notified 
that any disclosure, copying, distribution, or reliance upon the contents of 
this e-mail is strictly prohibited. If you have received this e-mail 
transmission in error, please reply to the sender, so that ICON plc can arrange 
for proper delivery, and then please delete the message.

Thank You,

ICON plc
South County Business Park
Leopardstown
Dublin 18
Ireland
Registered number: 145835

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RE: [NMusers] BAYES method and initial estimate bounds

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