one size fits all vs goal posts [NCA / SHAM]

posted by ElMaestro  – Denmark, 2019-02-16 14:33 (1886 d 14:02 ago) – Posting: # 19927
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Hi all,

also 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. This will work as long as the phenomena that we discuss (funky data points, imputation, deletion, addition, intellingent fixes) occur with equal probability across groups.
We may bias some estimate (like lambda) rather terribly either in positive or negative direction, but that does not automatically imply that the expected point estimate changes and therefore it may be entirely safe in term of patient's risk. "It depends" as they say.

For example, there was a post recently (Mittyri? Hötzi? Someone else?) who wrote that when we do log down in BE we assume a first order elimination. 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 :-) and that's how I am not necessarily strongly favouring one method over the other. 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.
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, I was only in situations where regulators questioned the proof of BE.

For dose-finding or superiority it may be a somewhat different situation.

❝ Another point is that I used PHX NCA like a standard candle (maybe regulators do it as well?). But it turns out that in some rare extreme cases it is worth to think about alternative approaches. Would it be accepted? How to be sure that the method stated in SAP would work better than PHX algo? Is it possible to explain in the report any disagreement with PHX output?

Regulators are using PHX now????

Pass or fail!

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