Covariate screening

4 messages 3 people Latest: May 31, 2001

Covariate screening

From: Peter Bonate Date: May 31, 2001 technical
From: peter.bonate@quintiles.com Subject: Covariate screening Date: Thu, 31 May 2001 07:59:09 -0500 Are there any published papers on whether covariate screening techniques (GAMs or other regression based methods) are the same, inferior,or superior to testing all possible covariate combinations within NONMEM? Thanks Pete Bonate

RE: Covariate screening

From: Mark Sale Date: May 31, 2001 technical
From: "Sale, Mark" <ms93267@GlaxoWellcome.com> Subject: RE: Covariate screening Date: Thu, 31 May 2001 09:45:58 -0400 All possible covariates? Stuart, Nancy Sambol and Janet Wades paper (J Pharmacol Biopharm, 22(2) 1994 - Interactions between structural, statistical and covariate models in population pk analysis) tells us that we cannot examine covariates in isolation, since interactions can occur. So we would need to look at all combinations of covariates. Lets see, if we have the basic covariates (age, wt, gender, race) on each of 4 basic parameters (V, CL, Ka, Lag), using each of two models (linear and exponential) in addition to no relationship we have: 3^4^4 = 43,046,721 possible models. Clearly we need some sort of screening. We recently had a poster at ASCPT looking at whether a machine learning method (genetic algorithm) can find the "best" among a finite set of candidate models (structural, error and covariate models), comparing it to exhaustive search. Basically it worked pretty well. At some point, we'll compare this "artificial intelligence" method prospectively to "natural intelligence" methods, assuming we can find some around here. Mark

Covariate screening #2

From: Peter Bonate Date: May 31, 2001 technical
From: peter.bonate@quintiles.com Subject: Covariate screening #2 Date: Thu, 31 May 2001 09:11:32 -0500 In my first note I asked: Are there any published papers on whether covariate screening techniques (GAMs or other regression based methods) are the same, inferior,or superior to testing all possible covariate combinations within NONMEM? Let me rephrase the question: Are there any published papers on whether covariate screening techniques (GAMs or other regression based methods) are the same, inferior,or superior to screening covariates within NONMEM? Thanks pete bonate

Re: Covariate screening

From: Mats Karlsson Date: May 31, 2001 technical
From: Mats Karlsson <Mats.Karlsson@farmbio.uu.se> Subject: Re: Covariate screening Date: Thu, 31 May 2001 16:14:01 +0200 Dear Peter, I don't know if anyone has done exhaustive looks at covariate modesl using NONMEM. It would be requiring quite a lot of runs for all but the simplest cases if you want to do statistical simulations. Two papers I know of (there may well be more) that address the issue at least partially are Jonsson EN, Karlsson MO. Automated covariate model building within NONMEM. Pharm Res. 1998 Sep;15(9):1463-8. and a paper by Kowalski et al. in the next issue of J Pharmacokin Pharmacodyn Best regards, Mats -- Mats Karlsson, PhD Professor of Pharmacometrics Div. of Pharmacokinetics and Drug Therapy Dept. of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 SE-751 24 Uppsala Sweden phone +46 18 471 4105 fax +46 18 471 4003 mats.karlsson@farmbio.uu.se