NONMEM Users Network Archive

Hosted by Cognigen

RE: MU referencing

From: Bob Leary <Bob.Leary>
Date: Mon, 27 May 2013 15:38:42 -0400

There is another theoretical issue - constraining two parameters to have t=
he same
mean (tvParam) but different etas (ETA(1) and ETA(2)) violates the fundamen=
tal assumption of MCPEM-like method
that the parameters are multivariate normal. The basic update formula for=
 the fixed effects based
on the means of the posteriors for the random effects is no longer valid. =
For example, in a standard formulation the mean of the posteriors over all
subjects must be zero (this is the basic EM first order stationarity condit=
ion for the derivative of the log likelihood function ).
But if you have two different means associated with the same eta, both mean=
s in general cannot both be simultaneously zero..
It is unclear if MCPEM will converge under these conditions, and even if it=
 does, there is no guarantee that
the point corresponds to maximum likelihood.

From: owner-nmusers
 Of Brendan Johnson [brendan.m.johnson
Sent: Sunday, May 26, 2013 2:54 PM
To: nmusers
Subject: [NMusers] MU referencing

Hi all,
When using MU referencing, how do I code the situation where the typical va=
lue appears to be the same between two groups, but one group is more variab=
le how do I give these two groups different ETAs but essentially the sa=

Is this legit?




Where G1 and G2 equal 0 or 1 based on which group the subject belongs.

Thanks for the advice,
Brendan NOTICE: The information contained in this electronic mail m=
essage is intended only for the personal and confidential use of the d=
esignated recipient(s) named above. This message may be an attorney-client =
communication, may be protected by the work product doctrine, and may =
be subject to a protective order. As such, this message is privileged and=
  confidential. If the reader of this message is not the intended recip=
ient or an agent responsible for delivering it to the intended recipie=
nt, you are hereby notified that you have received this message in error an=
d that any review, dissemination, distribution, or copying of this mes=
sage is strictly prohibited. If you have received this communication i=
n error, please notify us immediately by telephone and e-mail and destroy a=
ny and all copies of this message in your possession (whether hard cop=
ies or electronically stored copies). Thank you. buSp9xeMeKEbrUze
Received on Mon May 27 2013 - 15:38:42 EDT

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to:

Once subscribed, you may contribute to the discussion by emailing: