NONMEM Users Network Archive

Hosted by Cognigen

Re: nm7 IMP method question

From: Xavier Woot de Trixhe <xavier.wootdetrixhe>
Date: Wed, 12 May 2010 20:23:09 +0200

Hi,

SIGL=4 NSIG=1 seems low...
Are you sure this is not simply due to the propagation of numerical
errors caused by having to few significant digits?

K. Regards,
Xavier

Leonid Gibiansky wrote:
> I've seen on a number of examples (of non-linear differential
> equations models) the IMP method diverge (by increasing the OF
> indefinitely, until it hits infinity). In those cases, IMPMAP was more
> successful.
> Leonid
>
> --------------------------------------
> Leonid Gibiansky, Ph.D.
> President, QuantPharm LLC
> web: www.quantpharm.com
> e-mail: LGibiansky at quantpharm.com
> tel: (301) 767 5566
>
>
>
>
> Sebastian Ueckert wrote:
>> Dear Wu,
>> it is important to realize that the new estimation methods do not
>> directly maximize the likelihood. The EM algorithm updates the
>> population parameters by averaging the conditional mean/variances of
>> the etas. Therefore, it is not guaranteed that the likelihood
>> increases (OFV decreases). The classical method, opposed to that, are
>> gradient based and only change the population parameters when the OFV
>> decreases.
>>
>> There are several things you could try if the OFV is continuously
>> increasing when using the IMP method:
>> - make sure that your model is valid for unusual eta samples (prevent
>> e.g. division by zero, logarithm of values smaller than zero, etc.)
>> - change the initial values
>> - use a different estimation methods prior to IMP (e.g. FOCE, ITS)
>> - increase the number of individual samples (ISAMPLE)
>> - use a different sampling distribution (e.g. DF=1)
>> - try using the IMPMAP method instead
>>
>> It would be interesting to know if other users have additional
>> suggestions.
>>
>> Best regards,
>> Sebastian
>>
>> Sebastian Ueckert, MSc, PhD student
>> -----------------------------------------------
>> Pharmacometrics Research Group,
>> Department of Pharmaceutical Biosciences,
>> Uppsala University
>> -----------------------------------------------
>> P.O. Box 591
>> SE-751 24 Uppsala
>> Sweden
>> -----------------------------------------------
>> sebastian.ueckert
>> -----------------------------------------------
>> Work: +46-(0)18-471 4437
>>
>>
>> On Wed, May 12, 2010 at 5:30 PM, Xiao Hu <Xiao.Hu
>> <mailto:Xiao.Hu
>>
>>
>> *Dear Sebastian and Ethan,*
>>
>> I have encountered similar situation in the same estimation
>> step. It also occurred using Baysian method. The MCMCOBJ just kept
>> increasing from approximately -100 to 2000, while CONDITIONAL LAP
>> and FOCE converged successfully. I found different methods work for
>> different dataset and model structures. Changing initial estimation
>> did not help much. Any insight on why OBJ and MCMCOBJ keep
>> increasing, and how to prevent it would be helpful. Thanks in
>> advance.
>>
>> Best regards,
>> Shelley
>>
>> ========================================
>> Xiao Hu (Shelley), Ph.D.
>> Scientist,
>> Development Pharmacokinetics & Disposition
>> Biogen Idec, Inc.
>> 14 Cambridge Center
>> Cambridge, MA 02142
>>
>>
>>
>> *Sebastian Ueckert <sebastian.ueckert
>> <mailto:sebastian.ueckert
>> Sent by: owner-nmusers
>> <mailto:owner-nmusers
>>
>> 12-May-2010 11:08 AM
>>
>> Message Size: *6.2 KB*
>>
>>
>> To
>> nmusers <nmusers
>> cc
>>
>> Subject
>> Re: [NMusers] nm7 IMP method question
>>
>>
>>
>>
>>
>>
>>
>>
>> Dear Ethan.
>> if you use the IMP method to estimate your parameters, you do not
>> have to run a second IMP step. The ESTEP is run for every iteration
>> and if the OFV is stable during the last iterations you can just use
>> that. However the behavior you are describing is strange. It could
>> be related to different settings for both steps. Can you please send
>> the code for both $EST lines?
>>
>> Best regards,
>> Sebastian
>>
>>
>> Sebastian Ueckert, MSc, PhD student
>> -----------------------------------------------
>> Pharmacometrics Research Group,
>> Department of Pharmaceutical Biosciences,
>> Uppsala University
>> -----------------------------------------------
>> P.O. Box 591
>> SE-751 24 Uppsala
>> Sweden
>> -----------------------------------------------_
>> __sebastian.ueckert
>> <mailto:sebastian.ueckert
>> -----------------------------------------------
>> Work: +46-(0)18-471 4437
>>
>>
>> On Wed, May 12, 2010 at 4:13 PM, Ethan Wu <_ethan.wu75
>> <mailto:ethan.wu75
>> IACCEPT
>>
>>
Received on Wed May 12 2010 - 14:23:09 EDT

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request@iconplc.com.

Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.