NONMEM Users Network Archive

Hosted by Cognigen

Re: More Levels of Random Effects

From: Leonid Gibiansky <LGibiansky>
Date: Fri, 17 Oct 2008 09:30:12 -0400

Nick,

This is exactly what I meant. If you have a model for English, Irish and
Welsh, you may at least extrapolate it to Australians and New Zealanders
(of British descent :) ). With occasion treated as non-ordered
categorical covariate, you cannot extrapolate the model at all because
time cannot be repeated, so your covariate (occasion) will have
different value (level) at any future trial.

Leonid

--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566




Nick Holford wrote:
> Leonid,
>
> I dont understand what you mean by "we lose predictive power of the
> model: we do not know what will be
> the variability on the next occasion.".
>
> Or are you concerned about the situation where you have say 3 occasions
> and the IOV seems to be different on each occasion but you now want to
> predict the IOV for a future study on the 4th occasion?
>
> I agree it is hard to extrapolate to future occasions but this seems to
> be just like any other non-ordered categorical covariate - e.g. if we
> see differences between English, Irish and Welsh what difference would
> you expect for Russians? :-)
>
> Nick
>
>
> Leonid Gibiansky wrote:
>> Hi Xia, Nick
>> Technically, one can use different variances on different occasions but
>> then we loose predictive power of the model: we do not know what will be
>> the variability on the next occasion. One can use occasion-dependent IOV
>> variance to check for trends (for example, to investigate the time
>> dependence of the IOV variability, or to check whether the first
>> occasion (e.g., after the first dose of a long-term study) is for some
>> reasons different from the others) but the final model should have some
>> condition that specifies the relations of IOV variances at different
>> occasion (SAME being the simplest, most reasonable and the most-often
>> used option).
>>
>> Thanks
>> Leonid
>>
>> --------------------------------------
>> Leonid Gibiansky, Ph.D.
>> President, QuantPharm LLC
>> web: www.quantpharm.com
>> e-mail: LGibiansky at quantpharm.com
>> tel: (301) 767 5566
>>
>>
>>
>>
>> Nick Holford wrote:
>>> Xia,
>>>
>>> There is no requirement to use the SAME option. However, it is a
>>> reasonable model for IOV that it has the same variability on each
>>> occasion.
>>>
>>> If you dont use the SAME option then you just need to estimate an
>>> extra OMEGA parameter for each occasion you dont use SAME. You can
>>> test if the SAME assumption is supported by your data or not by
>>> comparing models with and without SAME.
>>>
>>> Nick
>>>
>>> PS Your computer clock seems to be more than 2 years out of date.
>>> Your email claimed it was sent in 17 Jan 2006.
>>>
>>> Xia Li wrote:
>>>> Dear All,
>>>> Do we have to assume the variability between all occasions are the
>>>> same when
>>>> we estimate IOV? What will happen if I don't use the 'same'
>>>> constrain in the
>>>> $OMEGA BLOCK statement? Any input will be appreciated.
>>>>
>>>> Best,
>>>>
>>>> Xia Li
>>>>
>>>> -----Original Message-----
>>>> From: owner-nmusers
>>>> [mailto:owner-nmusers
>>>> Behalf Of Johan Wallin
>>>> Sent: Wednesday, October 15, 2008 9:17 AM
>>>> To: nmusers
>>>> Subject: RE: [NMusers] More Levels of Random Effects
>>>>
>>>> Bill,
>>>> Is it really an eta you want, or is this rather solved by different
>>>> error
>>>> models for the different machines?
>>>>
>>>> If still want etas, one way would be to model in the same way as
>>>> IOV. In the
>>>> case of intermachine-variability you would have to assume the
>>>> variability
>>>> between all machines are the same... Or would you rather assume
>>>> interindividual variability is different with
>>>> different machine, and you then would want one eta for TH(X) for every
>>>> machine...? It depends on what you mean by different slope every day,
>>>> regarding on what your experiments like, but calibration differences
>>>> should
>>>> perhaps be taken care of by looking into your error model, eta on
>>>> epsilon
>>>> for starters...
>>>>
>>>> Without knowing your structure of data, a short example of IOV-like
>>>> variability would be:
>>>>
>>>> MA1=0
>>>> MA2=0
>>>> IF(MACH=1)MA1=1
>>>> IF(MACH=2)MA2=1
>>>> ;Intermachine variability:
>>>> ETAM = MA1*ETA(Y)+MA2*ETA(Z)
>>>>
>>>> PAR= TH(X) *EXP(ETA(X)+ETAM)
>>>>
>>>> $OMEGA value1
>>>> $OMEGA BLOCK(1) value2
>>>> $OMEGA BLOCK(1) same
>>>>
>>>> /Johan
>>>>
>>>>
>>>> _________________________________________
>>>> Johan Wallin, M.Sci./Ph.D.-student
>>>> Pharmacometrics Group
>>>> Div. of Pharmacokinetics and Drug therapy
>>>> Uppsala University
>>>> _________________________________________
>>>>
>>>>
>>>> -----Original Message-----
>>>> From: owner-nmusers
>>>> [mailto:owner-nmusers
>>>> Behalf Of Denney, William S.
>>>> Sent: den 15 oktober 2008 14:39
>>>> To: nmusers
>>>> Subject: [NMusers] More Levels of Random Effects
>>>>
>>>> Hello,
>>>>
>>>> I'm trying to build a model where I need to have ETAs generated on
>>>> separately for the ID and another variable (MACH). What I have is a PD
>>>> experiment that was run on several different machines (MACH). Each
>>>> machine appears to have a different slope per day and a different
>>>> calibration. I still need to keep some ETAs on the ID column, so I
>>>> can't just assign MACH=ID.
>>>>
>>>> I've heard that there are ways to do similar to this, but I have been
>>>> unable to find examples of how to set etas to key off of different
>>>> columns.
>>>>
>>>> Thanks,
>>>>
>>>> Bill
>>>> Notice: This e-mail message, together with any attachments, contains
>>>> information of Merck & Co., Inc. (One Merck Drive, Whitehouse Station,
>>>> New Jersey, USA 08889), and/or its affiliates (which may be known
>>>> outside the United States as Merck Frosst, Merck Sharp & Dohme or
>>>> MSD and in Japan, as Banyu - direct contact information for
>>>> affiliates is
>>>> available at http://www.merck.com/contact/contacts.html) that may be
>>>> confidential, proprietary copyrighted and/or legally privileged. It is
>>>> intended solely for the use of the individual or entity named on this
>>>> message. If you are not the intended recipient, and have received this
>>>> message in error, please notify us immediately by reply e-mail and
>>>> then delete it from your system.
>>>>
>>>>
>>>>
>>>
>>
>
Received on Fri Oct 17 2008 - 09:30:12 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.