Integrator options

From: "atul" <bvatul@ufl.edu> Subject: Integrator options Date: Sun, 14 Oct 2001 11:28:55 -0700 Hello All Could everybody share their views on this? I am using a regression program called SCIENTIST for analysis of PKPD data set. The software has interestingly six different integrator options: 1. Euler 2. Simple runge kutta 3. Error controlled runge-kutta 4. Burlisch-Stoer 5. Episode (Adams) 6. Episode (Stiff) For a simple data set (Pharmacokinetics etc) the Eulers method works fine. But when I am analysing a PKPD model which is relatively complicated (disease progression/disease reversal) with effect of drug and indirect response model. I find that Eulers method is not working well. The estimates touch values as low as E-16 or as high as E+05. The simplex procedure works but the Least Squares Estimation which I suppose is based on these methods is behaving strangely with Eulers method. There is no problem with a simple PKPD model or a simple indirect response model with Eulers method but inclusion of a disease progression makes it behave strangely. I then tried the Simple runge Kutta option and it is working very well. The estimates make much meaning and although it is very slow it still converges. If I use a episode (stiff) the starting values do not change at all and the program terminates. Can I use the runge kutta method? How can I decide if the estimates by this method are reliable in comparison to Eulers? I wish now to transfer my model to NONMEM. How can NONMEM be different here? Thanks in advance for your time Atul