Re: Question regarding Calculation Process in $DES BLOCK

Here is a little background on how it works. ADVAN routines such as ADVAN6 use a subroutine from third party sources to do the integration. For example, ADVAN6 calls DVERK from IMSL, ADVAN13 calls LSODA, etc. These subroutines are the ones that call DES. They call DES with various values of T during the integration ("advance") from T1 to T2. (T1 and T2 are beginning and ending event time. Typically, these are the times on a pair of event records.) The integrating subroutine may decide it has enough information after a call with a value of T that is not exactly T2 (might be a little less or a little more.) A change was made with NONMEM V so that, after an advance, DES is called by the ADVAN routine itself (i.e., $DES statements are evaluated) at the exact value of the event time. >From the NONMEM V Supplemental Guide of March 1998 (guides/supp.pdf): 39. Displayed DES-defined Items DES-defined items may be displayed in tables or scatterplots and are computed at the event time in the data record. With previous versions of PREDPP, the displayed items might have been computed at a slightly different time and might have had slightly different values. This fixes the difficulty that Luann mentioned. Paul says: A related caveat is that during integration between two time points, the value of data items (in the $DES block) are set to the values defined at the end time, not the start time. I'm afraid that I can't give you a good explanation for this design decision. Every variable displayed via $TABLE has the value that was calculated by the last call to DES with the current event record. This is not a design decision; it is inevitable. Values created by PREDPP for display by NONMEM are stored in a common area (formerly COMMON NMPRD4; now MODULE NMPRD4). To display values at the start time would require PREDPP to save the values and to restore that part of NMPRD4. This could be rather difficult. Also, Stuart Beal preferred to see DES-computed values at the end time and that is why the change for a final call to DES at the event time was made. This also explains why the values for the first event record of the individual are those from the last event record of the previous individual. If there is no advance in time, then there is no call to the integrating subroutine, and no call to DES, so the values in NMPRD4 are unchanged. Warning 48 was new with NONMEM V in 1998. Why did we not at that time add a call to DES from the ADVAN routine with the first event record? I can't remember. Stuart Beal may have been afraid that some of the computations in a complicated DES might fail with values from the first event record, whereas they were ok with values from the second and subsequent event records.