[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 - 11:17:41 EDT