inter- vs extra- [NCA / SHAM]

posted by Helmut Homepage – Vienna, Austria, 2019-02-12 03:20 (1891 d 13:39 ago) – Posting: # 19901
Views: 11,099

Hi Nastia,

❝ The more I get answers the more I have questions...

That’s what science is all about, right?

We learn more by looking for the answer to a question and not finding it
than we do from learning the answer itself.
  Lloyd Alexander

❝ Why do algorithms for inter- and extrapolation differ?

Sorry, ask Certara/Pharsight. ;-)

❝ Let's say that the last point is NA. Then PHX will calculate it via estimated λz suspecting log elimination not depending from the actual AUC calculation method.

I wouldn’t say suspecting but rather rightly assuming.

❝ ❝ By specifying the linear trapezoidal you tell PHX that you believe that the drug between time points is eliminated in zero (!) order

❝ Then why does it use lambda and log elimination for unknown samples and local slope and linear elimination for known samples? What's wrong with calculation by λz for the both cases?

Good question. I think that λz in any case would not be a bad idea because it is more reliable (i.e., taking information of samples with higher concentrations which are more accurate into account). On the same account I never had problems in using $$AUC_{0-\infty}=AUC_{0-\text{t}}+\frac{\widehat{C}_\text{t}}{\widehat{\lambda}_\text{z}}\tag{1}$$ instead of the simple $$AUC_{0-\infty}=AUC_{0-\text{t}}+\frac{C_\text{t}}{\widehat{\lambda}_\text{z}}\tag{2}$$ In Phoenix WinNonlin \(\small{(1)}\) is termed AUCINF_pred) and \(\small{(2)}\) AUCINF_obs. See also this article.

❝ Of course I can try to think about it as a compromis (see this post), but then how to define my own rule to be sure that it is correct?

Yep (you are an expert in using the forum’s search function and digging out old posts).
High time for us all to switch to AUCtlast (Common).*

❝ ❝ I always describe exactly what I plan to do in the protocol.

❝ That's a perfect position. But sometimes we have to work with what someone has planned before.

I know, I know…

❝ I was always wondering how far one can go in stating his favourite methods in SOPs and SAPs?

As I said above, very far. Maybe I was lucky? IMHO, in the SAP it’s easier because it is more specific to the study. In an SOP you likely end up with a crazy flowchart trying to cover all potential cases only to discover later that you have forgotten one.
NB, I don’t have a single SOP for NCA.

❝ Can I write that after the calculation a statistician should have a cup of tea? :-)

Or even? :party: Borderline.

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
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