RE: covariate selection question

From: Paul Hutson prhutson@pharmacy.wisc.edu Subject: RE: [NMusers] covariate selection question Date: Tue, 17 Jan 2006 22:50:33 -0600 Mark raises an interesting point that may be appropriate for comments from the Wise Ones. I typically consider model building in terms of increasing the number of exponential decay terms, then the covariates and etas trying to lower the objective function. Is it the standard of practice that the covariates are prospectively identified as being collected for inclusion in the model-testing, or are they tested in the model post hoc just because they are available from the exhaustive efficacy & safety testing seen with Phase I and II trials? Most fundamentally, should I declare the covariates to be tested before beginning a trial? but also, Should a higher standard (greater reduction) in the objective function be imposed when doing post hoc data mining because of the effect of repeated measures? I can see where the subsequent use of bootstrap testing tests the robustness of the contribution (value) of the covariate, but should the covariate even be have been accepted in the first place? Part of my concern is the future (maybe current for some of you?) testing of genotypic mutations as covariates of clearance and/or response. Thanks in advance for your wisdom. Paul -- Paul R. Hutson, Pharm.D. Associate Professor UW School of Pharmacy 777 Highland Avenue Madison WI 53705-2222 Tel 608.263.2496 Fax 608.265.5421 Pager 608.265.7000, p7856