All, Just a reminder that NONMEM VI and NONMEM 7.1.0 have a bug that may affect certain band matrices as noted in a previous bug alert (see excerpt below). This has been corrected in NONMEM 7.1.2. Tom 1. There is a bug in NONMEM VI 1.x & 2.0 and NONMEM 7.1.0 that results in the spurious error message below, or a similar message, when certain band symmetric matrices are defined in $OMEGA. PROGRAM TERMINATED BY OBJ OMEGA ESTIMATED TO BE SINGULAR MESSAGE ISSUED FROM ESTIMATION STEP AT INITIAL OBJ. FUNCTION EVALUATION Workaround: None is available.
________________________________ From: [email protected] [mailto:[email protected]] On Behalf Of Paolo Denti Sent: Friday, September 03, 2010 7:44 AM To: nmusers Subject: Re: [NMusers] Block versus diagonal omega Hi Al, as far as I can tell, if you have a BLOCK matrix in NONMEM, the only elements that you can fix to zero (without fixing the whole block) are the ones in the lower corner of the matrix. You can have lower triangular matrices of zeros as large as all of yours off-diagonal elements (in which case the matrix would become diagonal). To do this, you just set the initial estimate of those element to exactly zero. Don't write FIX anywhere in the block, or else NONMEM is going fix the values of the whole block. Some examples would be $OMEGA BLOCK(3) a b c 0 d e or $OMEGA BLOCK(4) a b c 0 d e 0 0 f g or $OMEGA BLOCK(4) a b c d e f 0 g h j Obviously, unless you are lucky, the zeros won't be where you want them to be with the numbering you chose for the ETAs, so you might need to change the order and bring all the zeros to the lower triangle. Lots of fun! ;) Some matrices can't be obtained this way unless you sacrifice some additional correlations, I fear. Or at least I can't see how. Like the one below: $OMEGA BLOCK(4) a b c d e f 0 0 g h The only way I can think to obtain exactly this one (someone else can maybe help here) is to calculate the Cholesky factor of your matrix so that you can rewrite it the whole thing in your code using only thetas. In that way you would be able free to fix whatever you want to any value. Hope this is not too confusing... Greetings from Cape Town, Paolo On 02/09/2010 22:39, Berg, Alexander K., Pharm.D., Ph.D. wrote: Everyone - Thank you all for your assistance in answering my question regarding the block versus diagonal omega structure. The answers that you all provided have been a great help thus far and are much appreciated. As a follow-up, I was curious if someone could point me towards a reference that would help me to figure out how to restructure the covariance into different omega blocks. Specifically, I would like to understand the basis and proper method for restructuring the omega block so that I may remove selected covariance terms when simplifying from a completely unstructured block to a more parsimonious one. Thanks again for your help and time - Al Berg -- ------------------------------------------------ Paolo Denti, PhD Post-Doctoral Fellow Division of Clinical Pharmacology Department of Medicine University of Cape Town K45 Old Main Building Groote Schuur Hospital Observatory, Cape Town 7925 South Africa phone: +27 21 404 7719 fax: +27 21 448 1989 email: [email protected] ------------------------------------------------ ICON plc made the following annotations. ------------------------------------------------------------------------------ This e-mail transmission may contain confidential or legally privileged information that is intended only for the individual or entity named in the e-mail address. If you are not the intended recipient, you are hereby notified that any disclosure, copying, distribution, or reliance upon the contents of this e-mail is strictly prohibited. If you have received this e-mail transmission in error, please reply to the sender, so that ICON plc can arrange for proper delivery, and then please delete the message. Thank You, ICON plc South County Business Park Leopardstown Dublin 18 Ireland Registered number: 145835
