From:"Stephen Duffull"Subject:[NMusers] Changing signifocant digits Date:Mon, 22 Jul 2002 12:13:33 +1000 Hi I have a general question. I recall hearing that changing the number of significant digits somehow changes the minimisation route. I do not understand how this is so. Oddly I have noticed that changing sig digits from say 3 to 4 can result in a successful minimisation for 4 whereas for 3 digits it did not. Any comments would be appreciated. Thanks Steve ***************************************** Stephen Duffull School of Pharmacy University of Queensland Brisbane 4072 Australia Tel +61 7 3365 8808 Fax +61 7 3365 1688 http://www.uq.edu.au/pharmacy/duffull.htm ------------------ From: VPIOTROV@PRDBE.jnj.com Subject:RE: [NMusers] Changing signifocant digits Date:Mon, 22 Jul 2002 09:31:33 +0200 It is quite often I observe the same behaviour. The common practice is (or has to be) rerunning the same problem with various SIGDIG (say, 3, 4 and 5) and select the best result. Note that with diff eq ADVANs TOL needs to be changed accordingly. Should be not less than SIGDIG+2. Best regards, Vladimir ------------------ From:Leonid Gibiansky Subject:Re: [NMusers] Changing significant digits Date:Mon, 22 Jul 2002 08:39:34 -0400 Hi Steve, My understanding is that there are some internal iteration loops that NONMEM runs until some precision is obtained. This precision is controlled (in addition to something else) by the number of significant digits required for the computations. Therefor, these loops stop at different points depending on the number of significant digits requested. Since the problem is highly non-linear, even small changes at each step may produce visible changes in the output. My impression is that there are several different places where the number of significant digits is used: one for internal convergences, and another one to estimate of the number of significant digits in the resulting parameter estimates. Sometimes the modeling process looks like hunting: when you request 3 significant digits, the problems stops with the message that you got only 2.5 digits. Requesting 4 results in 3.5. If you ask for 7, you get 6.3. I am not sure whether it is possible, but it would be helpful to have 2 parameters: one for internal computations and one for the final parameter estimates. Then you would be able to request all intermediate computations done with 5 significant digits, but would accept final output with 4 or 3 digits. Then this "hunting process" would result in convergence rather than disappointment. I usually do the following: if changes in requested significant digits (the hunt process described above) does not lead to any significant changes in the objective function (no more than 2-3-4 units) or in the parameter values (say, no more than 3-4%) then I view this as a technical issue that can be resolved by changing the initial values or even accepting the run if the number of digits in the result is more than 3. Alternatively, if changes in significant digits result in large changes of the OF or parameters, then the model is unstable and has to be corrected. Leonid ------------------