Dear all,
The NONMEM control file of Example 1 in the USERs GUIDE to NONMEM 7.2 pp. 108/128 tells us how to work with priors: ; Prior information to the OMEGAS (NETPxNETP of them). $OMEGA BLOCK(4) 0.2 FIX 0.0 0.2 0.0 0.0 0.2 0.0 0.0 0.0 0.2 ; Degrees of freedom to prior OMEGA matrix (1 for each Omega Prior block). ; Because degrees of freedom is very low, equal to the ; the dimension of the prior OMEGA, this means that the prior information to the OMEGAS is ; highly uninformative $THETA (4 FIX) This is what I use with NONMEM 7.2 ; when I follow the instruction and use inverse Wishart to represent the OMEGA of my previous NONMEM analysis (2500 conc in 200 patients). $OMEGA BLOCK(2) 0.000135 FIX 0.0000195 0.000640 ; I want to make the priors informative and calculated df according to the proposal by Mats. $THETA (138 FIX) ; when I do not follow the instruction and use simply the covariance matrix of the previous NONMEM analysis of the large data file: $OMEGA BLOCK(2) 0.000131 FIX 0.0000191 0.000627 $THETA (138 FIX) There is not really a big difference in my example. Joachim Joachim Grevel, PhD Scientific Director BAST Inc Limited BioCity Nottingham Pennyfoot Street Nottingham, NG1 1GF Tel: +44 (0)115 8120497 From: [email protected] [mailto:[email protected]] On Behalf Of Stephen Duffull Sent: 22 February 2012 17:46 To: Mats Karlsson; 'Joachim Grevel'; 'Coen van Hasselt'; 'nmusers' Subject: RE: [NMusers] OMEGA priors using modes of inverse Wishart matrix Hi An appropriate value for dof of the IW is difficult to determine. While it can be set at n-1 from a prior this is somewhat arbitrary. It is not in this sense like a t-distn where we calculate dof in this manner. You would have to get a feeling for the degree of spread in your deviates given your guess at OMEGA(0) and dof. This can be done by simulation or in special circumstances by direct calculation. Steve -- From: [email protected] [mailto:[email protected]] On Behalf Of Mats Karlsson Sent: Thursday, 23 February 2012 3:58 a.m. To: 'Joachim Grevel'; 'Coen van Hasselt'; 'nmusers' Subject: RE: [NMusers] OMEGA priors using modes of inverse Wishart matrix Dear Joachim, The IW distribution is not something you get from NONMEM, you have to give the degrees of freedom of the IW prior distribution. Normally this is at or below the number of subjects in you previous study depending the information about the parameter per subject. In addition to User’s Guides, you may find useful info in Gisleskog et al J Pharmacokinet Pharmacodyn. 2002 Dec;29(5-6):473-505. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala Phone: +46 18 4714105 Fax + 46 18 4714003 From: [email protected] [mailto:[email protected]] On Behalf Of Joachim Grevel Sent: 22 February 2012 15:24 To: 'Coen van Hasselt'; nmusers Subject: RE: [NMusers] OMEGA priors using modes of inverse Wishart matrix Dear Coen, There I do have the answer: with MCMC Bayesian in NONMEM 7.1 you have to use NWPRI according to the guide. Dear Nidal, What I try to do is that: use an existing very well defined popPK model (2500 conc in 200 patients) to obtain individual PK parameters in only 20 additional patients that have sparse sampling (2 to 4 conc per patient). I was planning to use informative priors rather than add 80 conc to a bulk of 2500 conc. What do you think? Thanks to all, specifically Tim! Joachim From: Coen van Hasselt [mailto:[email protected]] Sent: 22 February 2012 14:03 To: [email protected] Subject: Re: [NMusers] OMEGA priors using modes of inverse Wishart matrix Dear Joachim, I have always wondered about this particular question myself as well.. Thanks for asking at NMusers. Another thing related to the PRIORs I was wondering about: you can either use NWPRI (i.e. with the inverse wishart for OMEGA's), or TNPRI, which uses a multivariate normal for the OMEGA's. Do you have any idea when to use either of these two possible implementations ? Thanks, Coen >>> "Joachim Grevel" 02/22/12 2:11 PM >>> Dear NMusers, Our NONMEM User Guides are full of good advice and they are searchable. Yet when I tried to find out whether any of the estimation methods could be enticed to give me the ?inverse Wishart matrix? needed to specify PRIORS for OMEGAs, I found no help. Leonid G. mentions the inverse Wishart matrix in his historic contributions to NMusers, but again I could not find out how to obtain it. If it does not happen in NONMEM, is there a tool in R that can give me that matrix? Your help is greatly appreciated, Joachim Joachim Grevel, PhD Scientific Director BAST Inc Limited BioCity Nottingham Pennyfoot Street Nottingham, NG1 1GF Tel: +44 (0)115 8120497
