Differences in Covariance analysis between FOCE vs. IMPMAP

Dear NONMEM user The discussion about negative Eigenvalues during IMPMAP covariance analysis made me add this method after my standard FOCE run: $OMEGA BLOCK(2) 0.3 ;LOGETA_K40 0.1 0.3 ;LOGETA_K43 $OMEGA BLOCK(2) 0.3 ;LOGETA_K30 0.1 0.3 ;LOGETA_K34 $EST METHOD=0 PRINT=10 INTERACTION NSIG=3 SIGL=12 $EST METHOD=COND PRINT=10 INTERACTION NSIG=3 SIGL=12 MAXEVAL=3000 FOCE minimization and covariance analysis was SUCCESSFULL resulting in an OFV of 6239. Standard errors, theta and eta correlations looked reasonable: THETA:se% = 4.8 8.5 22.7 8.6 19.9 OMEGA:se% = 37.3 45.5 58.9 32.2 49.1 SIGMA:se% = 30.8 17.5 After adding the additional IMPMAP method my OFV becomes 6252 (not critical I think), standard errors increase (for one even dramatically), all thetas are correlated and eta correlations are mirrored in the band matrix: $EST METHOD=0 PRINT=10 INTERACTION NSIG=3 SIGL=12 $EST METHOD=COND PRINT=10 INTERACTION NSIG=3 SIGL=12 MAXEVAL=3000 FILE=FOCE_2WAY.TXT $EST METHOD=IMPMAP INTERACTION EONLY=1 ISAMPLE=1000 NITER=5 FILE=IMPMAP_2WAY.TXT THETA:se% = 13.1 17.7 28.8 34.0 20.6 OMEGA:se% = 59.9 43.9 26.0 248.4 84.3 SIGMA:se% = 40.3 18.3 What is happening here? What is my mistake here? Was I just lucky with the FOCE? Thanks for your help and comments Andreas ---------------------------------------------------------------------------------------------------------------------------------------- Andreas Steingötter, PhD Division for Gastroenterology and Hepatology Institut for Biomedical Engineering Department of Internal Medicine Divisions of Bioimaging and MRI Technology University Hospital Zurich University and ETH Zurich Rämistrasse 100 Gloriastrasse 35 CH - 8091 Zurich CH - 8092 Zurich Tel. +41 44 255 5684 Tel. +41 44 255 5684 Fax +41 44 255 4591 Fax +41 44 632 1193 Email [email protected] Email [email protected]