RE: [NMusers] Reporting Modeling Results

That's even better by including the recommended dosing regimens for =
different age/weight if the model results are directly used to guide =
dose administration for clinicians -after all, CL is just an =
intermediate parameter.

Alan

-----Original Message-----
From: Bruce Charles [mailto:b.charles1_at_uq.edu.au]
Sent: Wednesday, October 24, 2007 7:49 PM
To: Xiao, Alan; John Mondick; nmusers_at_globomaxnm.com
Subject: RE: [NMusers] Reporting Modeling Results


We have used the conversion-table approach a number of times before in =
trying to negotiate the translation from model to clinic. See Table 5 in =
the attached paper as an example.
Good luck.

Bruce CHARLES, BPharm(Hons), PhD, GradDipBusAdmin, MPS
Reader
School of Pharmacy
The University of Queensland, 4072 Australia
[University Provider Number: 00025B]
 
TEL: +61 7 336 53194
FAX: +61 7 336 51688
 
http://www.uq.edu.au/pharmacy/brucecharles/charles.html
b.charles1_at_uq.edu.au


-----Original Message-----
From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] =
On Behalf Of Xiao, Alan
Sent: Thursday, October 25, 2007 1:28 AM
To: John Mondick; nmusers_at_globomaxnm.com
Subject: RE: [NMusers] Reporting Modeling Results

An option to report your results to appease non-modelers in your case =
might be reporting your CL values in a table with different age and =
weight.

Alan


-----Original Message-----
From: owner-nmusers_at_globomaxnm.com =
[mailto:owner-nmusers_at_globomaxnm.com]On Behalf Of John Mondick
Sent: Wednesday, October 24, 2007 11:18 AM
To: nmusers_at_globomaxnm.com
Subject: [NMusers] Reporting Modeling Results


I would like to get some feedback from the group concerning the =
reporting of modeling results. I have a Pop PK model developed from data =
arising from 124 pediatric patients, age 1 to 48 months. All of the =
structural parameters have been scaled allometrically, with the median =
body weight used as the reference value. After accounting for body size, =
a covariate model was incorporated to describe maturational changes in =
CL for young children. The maturation of clearance was modeled using an =
exponential model proposed in:

Andersen et al. Population clinical pharmacology of children: modelling =
covariate effects. Eur J Pediatr. 2006

Two parameters are estimated as part of this model * the fractional =
change in CL for a typical one month old patient (beta - estimated to be =
0.76 (0.589, 0.96) for this analysis) and a maturational half-life (TCL =
- 3.82 (1.57, 6.95) months). CI's are from the bootstrap.

The problem that I am running into is how to report the modeling =
results. It seems very natural to me to report the model results =
normalized to median body weight (L/h/10.4 kg^0.75). One of the study =
investigators disagrees with me and would like to report the results on =
a per kg basis (L/h/kg^0.75). This seems to be counterintuitive to me, =
as I tend to think about what represents the "typical patient." It also =
makes no sense to me to represent the CL in a one kg child. The argument =
is that reporting in this manner makes more sense to clinicians and that =
there is no such thing as a typical child.

So in an attempt to appease the investigator, I fit the same model with =
no weight normalization. The estimated parameters are equivalent to what =
would be scaled from the weight-normalized model, but there is no =
covariance matrix (not surprising). It becomes problematic when the =
bootstrap results are considered * beta = 0.78 (0.005, 0.995), TCL = =
3.90 (0.001, 6.018). Again, this is not surprising given that the =
covariate model is not centered.

I have attempted to make several compromises, including reporting the =
parameter estimates in both median weight-normalized terms and =
normalized per kg. I have also included scaled CL estimates for typical =
patients at several ages and body weights. This hasn't met the approval =
of the investigator, who is now insisting that I report the model =
building procedure from the median weight model, but report scaled =
parameters only on a per kg basis. This is wrong in my opinion and is =
actually more confusing to someone who is trying to understand the =
model.

Can I get the group's opinion on this? Am I being stubborn looking at =
the world through a modeler's point of view?

Thanks,




John Mondick PhD
Research Assistant Professor
Division of Clinical Pharmacology and Therapeutics
The Children's Hospital of Philadelphia
Tel (267) 426-2292
FAX (215) 590-7544
Email: mondick_at_email.chop.edu

Received on Thu Oct 25 2007 - 08:04:11 EDT