Re: Covariate Models Using Weight

From: "Stephen Duffull" <sduffull@fs1.pa.man.ac.uk> Subject: Re: Covariate Models Using Weight Date: Fri, 19 Nov 1999 09:15:41 -0000 There has been considerable discussion about covariate models etc. I perceive that the discussion has slightly wider implications. Are covariates that have a mechanistic flavour better than those that do not (or none at all)? 1) If you have a choice of two covariates (eg creatinine clearance or serum creatinine). eg. If you have a renally cleared drug and you can use either estimated creatinine clearance (eg Cockcroft and Gault or Jelliffe & Jelliffe) as a covariate or some empirical model based on serum creatinine and both models yield the same objective function with the same number of parameters then which do you use? I personally prefer the generality of the creatinine clearance equation. The same is true for Nick's argument - if an allometric scaling factor has been developed that has generality outside of the particular experiment that is being considered currently and still predicts as well as an empirical choice then I personally would prefer using it (even if I could not substantiate the value of the power (3/4) in this particular experiment). 2) If a covariate does not improve the fit of your model do you include it? eg If adding WT^(?) as a covariate for Vd or CL does not alter the objective function significantly - then do you include it as a descriptor? This depends on why you are modelling (eg descriptive or predictive). If "predictive" then it would be difficult not to believe that larger people don't have larger Vd or CL - even if you couldn't show this based on the current experimental design. I don't think it is bad to include prior beliefs, as long as they have some basis in reality, in the model building exercise and indeed if the process needs to be formalised then a Bayesian solution may be appropriate. In both examples assumptions in model building need to be transparent to the user. Just a thought Steve ===================== Stephen Duffull School of Pharmacy University of Manchester Manchester, M13 9PL, UK Ph +44 161 275 2355 Fax +44 161 275 2396