Re: Centering (was Re: Missing covariates)

Date: Wed, 04 Jul 2001 11:29:44 -0400 From: Alan Xiao <Alan.Xiao@cognigencorp.com> Subject: Re: Centering (was Re: Missing covariates) Well, ..... About model development and application: 1). Whatever way you use to express a model (generally) should genuinely reflect the assumptions that the model has employed, the background that the model is based on and the possible limit (if any) that the model is applicable. If you use a centering value which is not consistent with your data from which the model is developed, the model will be confusing and sometime is misleading. Different centering will change the interpretability of the model although it might not change the applicability of the model. 2). Application of a model is different from development of a model so that they should not be messed up although the eventual objective of the model development is its application. If a drug was designed for people with mean age of 65 but the clinical trial was performed on patients with mean age of 50, and if this age range difference can result in significant difference in either PK model or PD response, then, this clinical trial design was bad and this bad situation probably can not be sufficiently corrected just by shifting the centering from 50 to 65. If the age range difference is not important (can not produce significant difference in PK and PD), centering at 50 should be better ( I think), since it tells what the model is based on. After all, application of a model is fundamentally just a complicated interpolation or extrapolation of the data (used to develop the model). The quality of this interpolation or extrapolation depends on the quality of the data samples, including the sampling quality, representativeness, etc. 3). Technically, I don't think this centering shift will simplify the application of the model, to any extent. Now back to my original question, I think I should rephrase that as the following: A). Does the (structural) model correspond to the mean values or median values of concentration data? B). Does the structural model correspond to mean or median values of covariates? They are tricky STATISTICAL questions, especially considering the realistic situations that most data distributions (of concentration, time, or covariates) are not ideally normal (lognormal). Thanks, To those American folks, Happy National Independence Day! Alan.