Dear nmusers, I'm working on a pharmacokinetic population analysis of a data set in NONMEM for my master thesis. The data set I'm analysing consists of 12 hours concentration-time profiles. A 2-compartment model with Erlang distribution describes the data well, and I'm now validating my model. However, I've run into some questions.
I've performed a data splitting analysis, and have some questions about predictive performance/simulation in NONMEM. 1. What is the difference between using different seeds and subproblems when doing a simulation? And how many seeds/subproblems are generally considered to be needed? 2. Simulating my subsets for the data splitting seems to give a over-prediction of the concentrations observed. Is there any way I can put in the C0/C2 concentration, in order to give NONMEM more information and hopefully better PRED when doing a simulation? Only age was found to be a significant covariate, and I suspect the reason for over-predicting the concentrations is that NONMEM needs more information. 3. When having different time measurements, how do I calculate out me (mean error) and rmse (root mean square error) for the subset; can I use the average for the different time measurements in the subset? Part of the inputfil: ID AMT TIME DV MDV SS II CMT AGE RATE 8 225 0 0 1 2 12 1 59 0 8 0 0 0 0 0 0 8 59 0 8 0 0.23 0 0 0 0 8 59 0 8 0 0.48 0 0 0 0 8 59 0 8 0 0.98 0 0 0 0 8 59 0 8 0 1.43 0 0 0 0 8 59 0 8 0 1.98 0 0 0 0 8 59 0 8 0 3.03 0 0 0 0 8 59 0 8 0 4.07 0 0 0 0 8 59 0 8 0 5.98 0 0 0 0 8 59 0 8 0 8.03 0 0 0 0 8 59 0 8 0 9.97 0 0 0 0 8 59 0 8 0 1.90 0 0 0 0 8 59 0 Part of the controlfile: $PROB $DATA $INPUT $SUBROUTINE ADVAN5 SS5; $MODEL $PK $ERROR $THETA (FIX 7.98) ; K12 (B) (FIX 27.2) ; Q/F (FIX 57) ; V8 (FIX 203) ; V9 (FIX 23.4) ; CL/F (FIX 0.107) ; age effect $OMEGA (FIX 0.06) (FIX 0.09) (FIX 0.27) (FIX 0.91) (FIX 0.02) $SIGMA (FIX 0.02) (FIX 1370) $SIMULATION (49682607) ONLYSIMULATION SUBPROBLEMS=10 $TABLE Your help is highly appreciated, thank you in advance. Best regards, Live Live Storehagen Master student Institute of Pharmacy University of Oslo Norway
