Hi Ronger,

Thanks for the information. I’ll have a look.

Warm regards,
Tingjie

From: Rong Chen <rongchen...@yahoo.com>
Reply-To: Rong Chen <rongchen...@yahoo.com>
Date: Sunday, 7 May 2017 at 12:55
To: "Guo, Tingjie" <t....@vumc.nl>, nmusers <nmusers@globomaxnm.com>
Subject: Re: [NMusers] Estimation method for ETAs with POSTHOC

Hi Tingjie,
I think this article could answer your question by indicating the objective 
function used to estimate post hoc eta and how to reproduce the estimate 
process in R. There were R codes example of a one-compartment PK model with 3 
etas to be estimated.
Title: R-based reproduction of the estimation process hidden behind NONMEM® 
Part 1: first-order approximation. URL: 
http://dx.doi.org/10.12793/tcp.2015.23.1.1

Best wishes,
Rong
________________________________
From: "Guo, Tingjie" <t....@vumc.nl>
To: nmusers <nmusers@globomaxnm.com>
Sent: Friday, 5 May 2017, 20:17
Subject: [NMusers] Estimation method for ETAs with POSTHOC

Dear NMusers,

I have two questions about the mathematical details on POSTHOC estimation in 
NONMEM. How does NONMEM actually do when doing POSTHOC ($EST METHOD=0 
MAXEVEL=0) to get ETAs? I assume but not for sure there is an objective 
function to be minimized, somewhat like:

      Objective function = SUM(Yobs-Ypred)^2/sigma^2 + 
SUM(Para_i-Para_pop)^2/omega^2

Is there an objective function used in NONMEM when doing POSTHOC? If so, what 
is that function?

Secondly, if the answer to above is yes, let’s assume the real objective 
function is the same as what I mentioned above. I wonder how (NONMEM does) to 
minimize this function? I am currently trying to do similar things in R/Python 
language. I tried Metropolis-Hasting algorithm and Simulated Annealing 
algorithm, but with some technical problems. And the result was not comparable 
with NONMEM as well. Can someone give me a direction for this? The more 
mathematically detailed the better.

Thanks!

Warm regards,
Tingjie



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