RE: no. of dummy points affect simulation and estimation results

From: Nick Holford n.holford@auckland.ac.nz Subject: RE:[NMusers] no. of dummy points affect simulation and estimation results Date: Tue, April 20, 2004 5:10 am Sandra, The inclusion of additional event records in the data file should not influence the solution in theory. However, in practice the DE solver may be sensitive to the requested output times. This is particularly likely if you have discontinuous DEs e.g. if you are modelling some process with a conditional expression in $DES. There are some special discontinuities (lag time and infusion duration) that the PREDPP library 'knows about' and can usually solve. I would suggest that you test your model by simulating it with a totally different piece of software e.g. WinNONlin, ModelMaker, Stella, Trial Simulator, etc. Make sure that your NONMEM simulated output is similar to the output of another program so that you can rule out coding errors. As far as I know NONMEM uses some kind of Gear method for ADVAN8. I cannot easily find any information on how ADVAN6 or ADVAN9 solve DEs. The stepsize is chosen automatically. All modern DE solvers do this. Only ancient methods let the user specify a stepsize. You might try increasing the value of TOL e.g. TOL=6 or higher to see if this helps to stabilize the solution by increasing the precision of the local error in the solutions. Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/