From: Chantal Csajka <Chantal.Csajka@chuv.hospvd.ch>

Subject: weighting

Date: Mon, 20 Aug 2001 16:38:54 +0200

 

Dear nonmem users,

I am currently modeling concentration data from routine patient care in a

TDM framework. Several patients showed concentrations deviating clearly

from the expectation and were therefore repeatedly sampled. I think this

results in biased parameter estimates, as the few deviant individuals

provided a lot of data points. Is there a way to weight the data, say by

the inverse of the number of observations per patient, so that NONMEM takes

into account the oversampling and limits the bias ?

 

Thank you

 

 

Chantal Csajka, PhD

Division of Clinical Pharmacology

Beaumont 6

CHUV 1011 Lausanne, Switzerland

tel: 021/ 314.42.57

fax: 021/ 314.42.66

email: chantal.csajka@chuv.hospvd.ch

 

******

 

From: Nick Holford <n.holford@auckland.ac.nz>

Subject: Re: weighting

Date: Tue, 21 Aug 2001 09:29:03 +1200

 

Chantal,

 

Chantal Csajka wrote:

>

> Dear nonmem users,

> I am currently modeling concentration data from routine patient care in a

> TDM framework. Several patients showed concentrations deviating clearly

> from the expectation and were therefore repeatedly sampled. I think this

> results in biased parameter estimates, as the few deviant individuals

> provided a lot of data points.

 

Your impression that there is bias from a few 'deviants' may be very reasonable but it is presumably based on prior knowledge about the drug obtained with more formal PK studies. If this is the case then you should consider the use of Bayesian prior constraints on the parameter estimates. This involves specifying the population mean and variance for each of the PK parameters. It can be done using an undocumented feature of NONMEM V version 1.1. You can find some details of this at:

http://www.cognigencorp.com/nonmem/nm/99aug052000.html

[search for "Winbuggy" in this page]

 

Nick

--

Nick Holford, Divn Pharmacology & Clinical Pharmacology

University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand

email:n.holford@auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556

http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm