Re: OMEGA matrix

Pavel, [Apologies if this appears for a 3rd time on nmusers - I sent it earlier but it did not show up yet] You made some remarks about NONMEM and Monolix which I don't fully understand. You wrote "Monolix allows us to set a single correlation to zero. NONMEM may require a different approach." Let me try to explain how I understand how correlations may be defined in NONMEM and Monolix. Imagine this NONMEM covariance block: $OMEGA BLOCK(5) 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 The Monolix GUI allows you to specify correlations between random effects in a very similar format (I omit the upper triangular off-diagonal elements because they are always the same as the lower triangular off diagonal elements). 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Using NONMEM this can be modified to a series of band matrices like this: $OMEGA BLOCK(5) 1 1 1 1 1 1 1 1 1 1 0 1 1 1 1 $OMEGA BLOCK(5) 1 1 1 1 1 1 0 1 1 1 0 0 1 1 1 $OMEGA BLOCK(5) 1 1 1 0 1 1 0 0 1 1 0 0 0 1 1 If you try to set up a band matrix with Monolix you will get an error: "The IIV covariance structure is not valid. It must be symmetric and block defined." If you set correlations to zero with the Monolix GUI you can only do this when you define blocks which are not linked in any way with another correlation (like the band matrices above) e.g. 1 1 1 1 1 1 0 0 0 1 0 0 0 1 1 You would specify this as two blocks for NONMEM like this: $OMEGA BLOCK(3) 1 1 1 1 1 1 $OMEGA BLOCK(2) 1 1 1 Best wishes, Nick -- Nick Holford, Professor Clinical Pharmacology Dept Pharmacology & Clinical Pharmacology, Bldg 503 Room 302A University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand office:+64(9)923-6730 mobile:NZ +64(21)46 23 53 email:[email protected] http://holford.fmhs.auckland.ac.nz/ Holford SD, Allegaert K, Anderson BJ, Kukanich B, Sousa AB, Steinman A, Pypendop, B., Mehvar, R., Giorgi, M., Holford,N.H.G. Parent-metabolite pharmacokinetic models - tests of assumptions and predictions. Journal of Pharmacology & Clinical Toxicology. 2014;2(2):1023-34. Ribba B, Holford N, Magni P, Trocóniz I, Gueorguieva I, Girard P, Sarr,C., Elishmereni,M., Kloft,C., Friberg,L. A review of mixed-effects models of tumor growth and effects of anticancer drug treatment for population analysis. CPT: pharmacometrics & systems pharmacology. 2014;Accepted 15-Mar-2014.