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Re: [NMusers] ETAs & SIGMA in external validation

From: Jakob Ribbing <jakob.ribbing_at_pharmetheus.com>
Date: Tue, 10 Apr 2018 15:19:26 +0200

Hi Ruben,

I think I misread Tingjies original posting as taking ABS(ETA), whereas =
his initial attempt was actually ABS(1+ETA), which is less problematic.
The latter would not bias simulations much if IIV is e.g. 30% CV, =
agreed.

However, as Tingjies is mainly interested in estimation, I believe that =
without the ABS-correction, no subject will have the EBE at ETA <= -1 =
for a parameter that could not be <=0.
Unless possibly in a subject which is a) uninformative on that parameter =
and b) where the eta is also part of an omega-block - a scenario which =
seems unlikely to me, but may occur in theory.

Implementing the ABS-korrection ETA=-1.2 would give the same solution =
(parameter value) as ETA=-0.8, but at a higher OFV for that subject.
It seems to me, if negative parameter values are only a problem in the =
eta search for the EBE, whereas the EBE for individual parameters are =
always positive, then it should be more straightforward to use FOCE, =
with the addition e.g.:
IF(PARA.LT.0.001) PARA=0.001
Probably, no subject will have such a low individual parameter value, =
when looking into the table output?
If there are any such subjects I would look for errors in the data set =
and nonmem code (as outlined in my initial reply).

The above concerns estimation.
In simulation (unless %CV is low), we may get a fraction of subject with =
PARA=0.001, which may be an unreasonably low parameter value.
Whether that is acceptable or not depends on the objectives and in this =
case there was no need for simulations even for model evaluation (?), so =
I will not elaborate further.

Cheers

Jakob




Received on Tue Apr 10 2018 - 09:19:26 EDT

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