Already AUClast: 🍏≠🍊 [NCA / SHAM]

Hi Relaxation,

» » 5. $$\small{_\textrm{partial}AUC_{\textrm{cut off}-{\tau}}}$$
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» This one I think should be: $$\small{_\textrm{partial}AUC_{\textrm{cut off}-t_\textrm{last}}}$$?

According to the GL, yes. However, doesn’t make sense to me.1 In trying to get a waiver for the MD study I’m interested in showing BE for the partial $$\small{AUC\textrm{s}}$$, which are – hopefully – predictive of the clinical situation (multiple doses administered with $$\small{\tau}$$). If you have issues with the LLOQ in the SD study or missing sample(s) in the late part of the profile, already $$\small{AUC_{0-t_\textrm{last}}}$$ [sic] is a pile of poo.

If in a subject $$t_\textrm{last(T)}\neq t_\textrm{last(R)}$$, that’s comparing apples with oranges (though similar by weight and shape, extremely different by smell, taste, touch, and texture).
IMHO, it’s high time to abandon $$\small{AUC_{0-t_\textrm{last}}}$$ in all guidelines (because biased) and move forward to the – always (‼) unbiased – $$\small{AUC_{0-t_\textrm{last(Common)}}}$$.2

Confession: In my studies of multiphasic products I chickened out and used still $$\small{AUC_{0-t_\textrm{last}}}$$ (I knew that I won’t have problems with BQLs and wanted to make assessors happy) but $$\small{_\textrm{partial}AUC_{\textrm{cut off}-{\tau}}}$$. Were accepted without problems.

1. Remember Henning’s credo of ‘Science-based Regulations’!
2. Fisher D, Kramer W, Burmeister Getz E. Evaluation of a Scenario in Which Estimates of Bioequivalence Are Biased and a Proposed Solution: tlast (Common). J Clin Pharm. 2016; 56(7): 794–800. doi:10.1002/jcph.663. free resource.

Dif-tor heh smusma 🖖
Helmut Schütz

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