Re: Reporting Modeling Results

Hi John, I think you can safely separate statistics/mathematics and clinical use. I would fit the model in the shape and form suitable to get the best results (normalized to a typical patient in your case) and then report the results in the form most convenient for the clinical use. If this is per-kg values, then report it as they request. If you look in the literature, results are routinely reported as V/kg or CL/m^2, etc. On a side not, I am actually surprised that you got different results with different scaling. For the allometric scaling with fixed power, two parameterizations: CL=TCL*WT^0.75 and CL=TCL*(WT/10)^0.75 differ by the fixed factor (1/10)^0.75 = 0.18 I am not sure how this can influence your model CI so strongly. I would check how you stratify the bootstrap data sets. Could it be that stratification on something else depend on parameterization? If you would estimate the power: CL=TCL*(WT/10)^THETA() then parametrization would be more likely to affect CI, but for the fixed power I would look for other explanations of the differences. It would be easier to discuss the model if you would attach the PK block of the nonmem code. Leonid -------------------------------------- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web: www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel: (301) 767 5566 John Mondick wrote: > 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]