RE: Reporting Modeling Results

-----Original Message----- From: Bruce Charles [mailto:[EMAIL PROTECTED] Sent: Wednesday, October 24, 2007 7:49 PM To: Xiao, Alan; John Mondick; [email protected] 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 [EMAIL PROTECTED] -----Original Message----- From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On Behalf Of Xiao, Alan Sent: Thursday, October 25, 2007 1:28 AM To: John Mondick; [email protected] 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: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] Behalf Of John Mondick Sent: Wednesday, October 24, 2007 11:18 AM To: [email protected] 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: [EMAIL PROTECTED]