RE: covariates

From: "Leonid Gibiansky" leonidg@metrumrg.com Subject: RE: [NMusers] covariates Date: Fri, September 17, 2004 7:29 am Nick I do not question allometric scaling law described in the papers that you cited. I question an assertion that this law implies CL, Q_i~WT^(3/4), V_i~WT dependences for each and every drug. This is a good guess that should be checked and corrected if needed. Any compartmental model is just a crude approximation of the very complicated biological processes, and it is hard to expect that coefficients of that approximation behave exactly as CL~WT^(3/4), V~WT for every drug. If data contradict these dependencies, one should follow the data rather than impose artificial restriction on the model. In particular, if the model without WT describes the data better than the one with WT (better in terms of model diagnostic: e.g., observed vs. predicted plots stratified by WT) I do not see why should one ignore it. For covariate search, I advocate common sense rather that OF search: you should look on diagnostic (random effect versus covariate plots) in addition to OF. There are also statistical approaches to multiple testing (roughly, if you conduct a lot of tests, you should be more stringent in terms of OF drop in order to claim significance). But OF drop is a good measure for a quick screening of multiple covariates. Leonid