modeling interoccasion variability

From: "Panetta, Carl" Carl.Panetta@stjude.org Subject: [NMusers] modeling interoccasion variability Date: 11/18/2003 11:24 AM I have a question on modeling interoccasion variability (IOV). I have read through and used the method of handling IOV discussed in Karlsson and Sheiner (JPP 1993) and it works fine when there are 2 or 3 occasions per individual. But, in situations where there are many more than 3 occasions per individual and each individual does not necessarily have the same set of occasions, the method becomes more difficult to implement and NONMEM does not always converge successfully and/or give acceptable results. For example, I am working with a set of data where there are 10 different occasions. Not every individual has PK samples for each of the 10 occasions, but each individual has about 3 to 5 occasions. Thus, while everybody has an occasion 1 and most have an occasion 3 only a few have occasion 2. Therefore, instead of having a measure of variability for each of the 10 occasions separately, I would like to have a single overall measure of variability for the IOV for clearance (and other PK parameters) in a similar manner as I can get a single measure of the interindividual variability measure. Does anybody have any suggestions, references, etc. on if and how this can be done? Thanks, J. Carl Panetta, Ph.D. Department of Pharmaceutical Sciences St. Jude Children's Research Hospital 332 N. Lauderdale St. Memphis, TN 38105 Phone: (901) 495-3172 Fax: (901) 525-6869 Carl.Panetta@stjude.org