Re: missing data items

From: Mats Karlsson <Mats.Karlsson@biof.uu.se> Subject: Re: missing data items Date: Mon, 11 Sep 2000 20:47:48 +0200 Dear Paul and Lewis, In addition to Lewis 5 options I think one more can be added. We can create a model for the covariate. To do this we should have repeated measures of the covariate or knowledge of its inter or intraindividual variability. For the case there are systematic changes in the covariate with time, a model for these would also be required. If we think of PK/PD modelling, the drug concentration is only a covariate for the pharmacodynamic response, and we are seldom bothered by missing PK data when we performe a PK/PD modelling where concentrations and effects are simultaneously modelled. Similarly drug concentration is a covariate for metabolite concentration, plasma concentrations a covariate for urine output, etc. So we have extensive experience of handling missing covariate values when we have a model for the covariate. It is often not difficult to create a model for many of the covariates we apply. We either can set the intraindividual error to minimal (AGE, HT, WT) or we know the interindividual distribution characteristics well (SEX, GENO). The problem mainly lies in that there are so many covariates that doing this is a pain. Additional problems are that NONMEM haven't easily handled the combination of (continuous) PK or PD data with categorical (covariate -SEX,GENO) data. Best regards, Mats -- Mats Karlsson, PhD Professor of Biopharmaceutics and Pharmacokinetics Div. of Biopharmaceutics and Pharmacokinetics Dept of Pharmacy Faculty of Pharmacy Uppsala University Box 580 SE-751 23 Uppsala Sweden phone +46 18 471 4105 fax +46 18 471 4003 mats.karlsson@biof.uu.se