SAEM and IMP
Hello NONMEM Users,
As SAEM does not provide a useful objective function, the manuals recommend using IMP after SAEM. It works well in many cases when IMP works well. When IMP works well, SAEM is not always needed. SAEM is really needed when the other methods do not work well.
The issue is that there are hard cases when SAEM works very well and IMP does not work at all. SAEM provides meaningful and consistent PK/PD parameters across very different runs, while IMP provides objective function, which varies so greatly that it looks meaningless. Another potential issue with IMP is that even when it works well with a problem, it occasionally provides low values of objective functions after SAEM or as the first estimate (less frequently in the middle of IMP run) and then becomes unstable or jumps to much higher objective function and then converges to something between the low and the high values for a long time. It almost looks like IMP does not show some kind of integration/computation errors and keeps running providing a funny objective function.
It seems like we cannot estimate objective function when SAEM runs well and IMP does not. It reduces the value of SAEM. Is there a way around it?
Thanks,
Pavel