Another(?) ADVAN5 Problem

This note is addressed to all nonmem users using a VAX/VMS system (our version is 5.5-2). The problem we are facing is that when we run a simple 2 compartment model using advan5 the program ends even before the iteration process is invoked (the VAX gives a divide by zero error message in the DDDFRS routine line 23). Yet the same code and data set run successfully on a SUN system. If any users have some suggestions as to what we can try we would be most appreciative. (Interestingly a one compartment model runs without any problem)

In any event, sorry, there are no 'settings' that will help ADVAN5. I presume that you all include the NOABORT option on the $ESTIMATION record so that NONMEM can back away from the "bad" thetas and try values closer to the last good set of thetas. Gary originally said: The problem we are facing is that when we run a simple 2 compartment model using advan5 the program ends even before the iteration process is invoked (the VAX gives a divide by zero error message in the DDDFRS routine line 23). David, are you trying Gary's problem on your Vax? If so, the fact that no divide by zero occured points to some problem with the installation on Gary's Vax. I suggest that PREDPP be read in from the original installation tape, and that Gary verify that the source code for ADVAN5, REXPON, and RXSUBS is exactly as read. Recompile them too. Another possibility is that Gary uses a different (later?) version of FORTRAN than David, or that he uses different compiler options. Gary might try compiling without optimization, for example.

VAX/VMS is not IEEE-based, that is, the precision of calculations is less than on other systems. Probably Sun is IEEE-based (as is IBM, for example). I try to circumvent these kind of errors by trying different sets of initial estimates for the thetas. After a while iterations start, and one can try to guess a certain direction. (I work with the same version of VMS). I hope this is of some help.

I was able to modify an example I had to run under ADVAN5 on the VAX [6610 VMS 5.5] as a fitting exercise without any errors. However I did stop it short (by reducing the MAXEVALS, it was taking too long). I then developed a simple fitting problem with one subject and it ran fine with ADVAN5 and ADVAN4, except for the S MATRIX ALGORITHMICALLY SINGULAR (with both ADVANs) which I guess is due to the small number of data points. These were very simple examples but they seem to work. I would have compiled the program with the FORTRAN default settings. I'd be happy to try a bigger problem - I hadn't used these ADVANs before so may have made an error somewhere. .....

I followed the installation guide for installing with the listed adjustments. In the code attached, when I made a modification, I used a lower case c to comment out the original code. Double precision code was installed. Install steps executed: 2.1.1 - file name change to redirect output 2.1.3 - changed to VAX values indicated on page 17 2.4a - NONMEM project team change - DATA SMALLS from 10e-40 to 10e-38 2.5 - change OPEN statements to open FSTREAM as old when running NONMEM from NMTRAN procedure 2.7 - increase number of observations per subject from 50 to 500 Compiled code with command: FORTRAN/LIST/NOOP/NOF77 NONMEM This should provide a start.