Hi Steve, For a one-compartment model I think these are differences:
1) DIAG(3) is more restrictive than BLOCK(2) in the sense that only positive correlation between CL/F and V/F can be estimated 2) DIAG(3) is less restrictive than BLOCK(2) in the sense that different transformations can be used for F 3) DIAG(3) provides an EBE that can be used for diagnostic purposes (DIAG(3) and BLOCK(2) would give the same estimates for the same model so I don't understand your comment of var(F) being higher than cov(CL/F,V/F)) 4) DIAG(3) may facilitate covariate model building (although this is minor as you with BLOCK(2) can put the same relationship in in two places) 5) If there truly is a mixture in F1, then I think DIAG(3) has a advantages over BLOCK(2) in number of parameters (two fewer) needed to describe the variability model 6) If some additional assumptions can be reliably made, such as all variability in F1 is truly in bioavailability and bioavailability is restricted to be between 0 and 1, some additional info may be extracted from the data for example by . I would not rank any of these as major differences (expect possibly the mixture aspect which I've never tried). For two- or three-compartment models the advantages are that if indeed the main covariance structure between CL/F, V1/F, Q/F, V2/F is a joint positive correlation due to variability in bioavailability, fu etc, then a DIAG(5) is more parsimonious than a BLOCK(4). Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 -----Original Message----- From: Stephen Duffull [mailto:stephen.duff...@otago.ac.nz] Sent: Thursday, April 16, 2009 10:13 AM To: Mats Karlsson; drmo...@pri-home.net; nele.pl...@nycomed.com; nmusers@globomaxnm.com Subject: RE: [NMusers] OMEGA BLOCK with mixture model? Mats > With oral data only I would normally model with BLOCK(2) on > CL/F and V/F or a DIAG(3) on CL/F, V/F and relative F. The > latter may have some advantages for diagnostics, covariate > model building etc. I have often seen these two options considered. I am unclear as to the advantages of DIAG(3) over BLOCK(2)? In theory it would seem that they should be identical. In practice it seems that DIAG(3) is more relaxed since it is not required that the variance of relative F if reassigned to the covariance of (CL/F, V/F) [under BLOCK(2)] yields a positive definite matrix. I presume an advantage wrt covariate model building would be access to the EBEs of F_i. However, given the variance of F_i may exceed the covariance of (CL/F, V/F) then I wonder if this is a real advantage or an artefact of numerical procedures? I am keen to learn more about real advantages of application of DIAG(3) as an alternative to BLOCK(2). Steve -- Professor Stephen Duffull Chair of Clinical Pharmacy School of Pharmacy University of Otago PO Box 913 Dunedin New Zealand E: stephen.duff...@otago.ac.nz P: +64 3 479 5044 F: +64 3 479 7034 Design software: www.winpopt.com
