Re: Problem with initial values of the omega matrix with nonmem 7.6

________________________________ From: [email protected] <[email protected]> on behalf of Sebastiaan Sassen <[email protected]> Sent: Wednesday, March 18, 2026 5:57 AM To: [email protected] <[email protected]> Subject: [External] [NMusers] Problem with initial values of the omega matrix with nonmem 7.6 Dear colleagues, I ran into a problem with the omega matrix in nonmem 7. 6 for a model I received (simple FOCE+I advan3 trans4 nothing special). In the model file it is specified like this (I tried different notations as simple decimals, scientific Dear colleagues, I ran into a problem with the omega matrix in nonmem 7.6 for a model I received (simple FOCE+I advan3 trans4 nothing special). In the model file it is specified like this (I tried different notations as simple decimals, scientific notation etc. to no avail): $OMEGA BLOCK(3)   0.107               ; CL   0.48E-1 0.11          ; V1   0.42E-1 0.56E-1 0.084  ; V2 However, with nonmem 7.6 I get a problem with the initial estimates of omega. If I look at the list file I see that it is due to my omega block, which makes sense as the correlations between these values used as initial values of etas are not valid (outside of -1,1). However, these initial estimates are not the ones I provided. Compare this to the same exact model ran on nonmem 7.4.4. Here the initial omega estimates are as described in the model and it runs well. Even in a clean folder without any files other than the dataset (csv) and the model file (mod). Am I doing something wrong or is this something else? Nonmem 7.6: INITIAL ESTIMATE OF OMEGA HAS A NONZERO BLOCK WHICH IS NUMERICALLY NOT POSITIVE DEFINITE 0INITIAL ESTIMATE OF OMEGA: BLOCK SET NO. BLOCK FIXED 1 NO 0.1000E+01 0.4000E+01 0.1000E+01 0.4000E+01 0.5000E+01 0.8000E+01 Compared to nonmem 7.4.4, which seems to do this correctly:      0INITIAL ESTIMATE OF OMEGA: BLOCK SET NO. BLOCK FIXED 1 NO 0.1070E+00 0.4800E-01 0.1100E+00 0.4200E-01 0.5600E-01 0.8400E-01 Best regards, Sebastiaan ******************************************************************** This e-mail and any attachment hereto, is intended only for use by the addressee(s) named above and may contain legally privileged and/or confidential information. If you are not the intended recipient of this e-mail, any dissemination, distribution or copying of this email, or any attachment hereto, is strictly prohibited. If you receive this email in error please immediately notify me by return electronic mail and permanently delete this email and any attachment hereto, any copy of this e-mail and of any such attachment, and any printout thereof. Finally, please note that only authorized representatives of Regeneron Pharmaceuticals, Inc. have the power and authority to enter into business dealings with any third party. ********************************************************************