Dear users, I am modeling a PK data set with sparse data (2-3 samples/ind,~250 individuals). When I plotted TPST vs Conc, I do have a reasonable spread of concentrations across the PK profile. I started modeling (2-comp better model) with FOCEI and was getting numerical difficulties and wanted to use the EM based methods in NM7.2 I used ITS followed by SAEM and IMP as below with an intention to use quick ITS run for passing better (?) initial estimates to SAEM and then IMP for standard errors and objective function evaluation: $EST METHOD=ITS INTERACTION FILE=EXAMPLE1.EXT NITER=500 PRINT=5 NOABORT SIGL=4 CTYPE=3 CITER=10 CALPHA=0.05 NOPRIOR=1 NSIG=2 $EST METHOD=SAEM INTERACTION NBURN=5000 NITER=500 PRINT=100 SEED=1556678 ISAMPLE=2 $EST METHOD=IMP MAPITER=0 INTERACTION EONLY=1 NITER=5 ISAMPLE=3000 PRINT=1 SIGL=8 NOPRIOR=1
I got the following for each estimation method for termination message: ITS method- OPTIMIZATION NOT COMPLETED SAEM- Stochastic mode: Convergence Achieved STOCHASTIC PORTION COMPLETED REDUCED STOCHASTIC PORTION COMPLETED IMP- OPTIMIZATION NOT COMPLETED My parameter estimates from SAEM make good sense to the previous reports and SEs from IMP are reasonable. Questions: 1. How important for me to increase ITS iterations to bring optimization to be successful for passing initial estimates to SAEM? What to do if ITS never gets successful optimization after increasing iterations, it is likely given sparse data? 2. Which method gives a better estimate of correlation matrix and condition number (calculated from Eigenvalues)SAEM or IMP? 3. Are SEs valid from IMP as the termination message says "optimization not complete". Please suggest tips for getting IMP optimization to be complete. 4. If I continue to make changes to model, can I use IMP OBJ value similar to FOCEI OBJFUN value? I appreciate your guidance and referring me to any literature regarding these questions. Regards, Ayyappa Regards, Ayyappa
