RE: BOV

From: "Nick Holford" n.holford@auckland.ac.nz Subject: RE: [NMusers] BOV Date: Wed, September 22, 2004 4:56 pm Ken, Thanks for this additional result showing that NONMEM appears to be able to estimate 3 levels of random effect for this design. There is no need to offer any apologies :-) This discussion has been most helpful in clarifying ideas and understanding the limitations and opportunities for BOV. You (and Yaning) were certainly right in predicting that the estimate of BSV is biased upwards. A point I did not appreciate myself until I looked at the Excel simulations and realized from the numerical example what was happening. Yaning, I am still puzzled by your theoretical comments: "2. Complex scenario When we assume BOV is different for all occasions, this leads to a quite unusual assumption in the ANOVA setting as demonstrated by the following derivation. CLij=CL+ai+bij, CL is the true CL for the whole population, ai is the random subject effect, bij is the random occasion effect within a subject. ai~N(0, BSV), i=1,..., t, bij~N(0, BOVj), j=1,..., r, (Note BOV has a subscript now!) In this case, the replicates (occasions) come from different distributions. I went through some math/stat derivation and found the following conclusions. The individual BOVj is not estimable. " The way you have written the model seems to be the same as the way it was simulated by Mats (NONMEM) and myself (Excel). We both claim empirically that BOVj values are estimable. Yet you conclude "individual BOVj is not estimable". Can you please explain? Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/