Re: Model building question

From: mark.e.sale@gsk.com Subject: Re: [NMusers] Model building question Date: Tue, March 1, 2005 8:30 am Nick, I have to take exception to your comment "The sequence of model building should not affect the results but sometimes it does " I think, that it should be expected that the sequence of model building will affect the result. The only condition in which the sequence does not affect the outcome is when all of the various effects are independent, which is probably essentially never true in biology (or life in general). A trivial and/or contrived example. You have a pk data set with two covariates, kg and lb (unknown to you, both measuring body weight). If you put kg in first, you'll find no effect of lb, and vice versa, because the same information is contained in both. Janet Wade demonstrated the same to be true for structural effects, and our local experience with more robust search methods suggests that the same is true of residual error, and interindividual error terms. The outcome is always very sensitive to the sequence of "hypothesis tests". I've been told by those who formally study combinatorial optimization (which is what we are doing in our model building) that our algorithm is really, really naive. Mark Sale M.D. Global Director, Research Modeling and Simulation GlaxoSmithKline 919-483-1808 Mobile 919-522-6668