Bioequivalence and Bioavailability Forum

inter- vs extra- [NCA / SHAM]

posted by Helmut  – Vienna, Austria, 2019-02-12 03:20 (1893 d 18:32 ago) – Posting: # 19901
Views: 11,133

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 λ_z 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 λ_z for the both cases?

Good question. I think that λ_z 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 AUCt_{last (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? Borderline.

---

• Fisher D, Kramer W, Burmeister Getz E. Evaluation of a Scenario in Which Estimates of Bioequivalence Are Biased and a Proposed Solution: t_last (Common). J Clin Pharm. 2016;56(7):794–800. doi:10.1002/jcph.663. Open access.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна! 
Helmut Schütz


The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

• AUC0-tau at steady state BNR 2016-03-31 22:46 [NCA / SHAM] 
  • AUC0-tau at steady state jag009 2016-03-31 23:05
    • AUC0-tau at steady state BNR 2016-03-31 23:43
      • RTFM Helmut 2016-04-01 00:59
        • RTFM BNR 2016-04-01 02:05
        • AUC0-τ estimation with time deviations Astea 2019-02-10 16:38
          • AUC0-τ estimation with time deviations Helmut 2019-02-10 19:32
            • Cτ for lin and lin-up/log-down Astea 2019-02-10 20:50
              • Cτ by lin-/lin, lin-up/log-down, and λz Helmut 2019-02-11 01:45
                • inter- vs extra- Astea 2019-02-11 19:46
                  • inter- vs extra-Helmut 2019-02-12 02:20
                  • No rule fits all mittyri 2019-02-14 12:55
                    • one size fits all vs goal posts Astea 2019-02-16 08:33
                      • one size fits all vs goal posts ElMaestro 2019-02-16 13:33
                        • Bias etc. Helmut 2019-02-16 14:26
                      • software: NCA not validated Helmut 2019-02-16 13:59
                        • no way out for NCA validation? mittyri 2019-02-20 21:22
                      • Default rules mittyri 2019-02-20 21:40