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 Wed Oct 24 2007 - 11:28:03 EDT