Bioequivalence and Bioavailability Forum • Bias etc.

Bias etc. [NCA / SHAM]

posted by Helmut – Vienna, Austria, 2019-02-16 15:26 (2056 d 18:43 ago) – Posting: # 19929
Views: 12,322

Hi ElMaestro

❝ […] remember that when we do BE we treat T and R in the same fashion. So regardless of how terrible we bias some estimate we may do that equally for the two treatments we are comparing.

Reads nice on paper but people might be tempted to fiddle around if they are already unblinded before performing NCA. Hence, my sequence is:

Import necessary data (doses, dosing times, actual sampling time points, measured concentrations).
Perform NCA in a blinded manner (in PHX-lingo: Sort the dataset by subject and period).
Lock the results.
Import the randomization and join the respective tables.

Actually I even don’t have the randomization beforehand. I ask the sponsor or CRO for it after #3. Hence, nobody can blame me that I didn’t “treat T and R in the same fashion”.

❝ […] there was a post recently (Mittyri? Hötzi? Someone else?) …

Myself for sure. I’m notorious for that.

❝ … who wrote that when we do log down in BE we assume a first order elimination.

Yep.

❝ That is much a personal interpretation, I think. When I do log or linear down in BE, I am personally only saying I am willing to make the same error for T and R regardless of how the drug is eliminated, full stop :-)

Agree, if (!) there are no missings. OK, one exception: Same time point missing in the same subject.

❝ Even if the SPC or FOI info indicates first order elimination I am perfectly fine with lin. down especially if this is what the CRO usually does well. Wouldn't want them to get out of their comfort zone.

If the linear trapezoidal defines the comfort zone of a CRO it disqualifies itself (linear-up / log-down is implemented in software for ages). If someone isn’t able to RTFM and push yet another button, well…

❝ From the top of my head, I believe I have never been in a situation where I needed to defend an AUC value per se, …

Not AUC but I was once asked whether my software for NCA was validated (see there). Funny enough, the agency asked for cross-validation [sic] against “commercial software like WinNonlin” as if commercical software is the gold standard.

❝ Regulators are using PHX now????

The FDA does (modeling). The Saudia FDA does (BE, though additionally to SAS).

—
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Helmut Schütz

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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