Bioequivalence and Bioavailability Forum

Dear Helmut,

IMHO generally it would be "Good mathematical practice" not to round intermediate results. At least I was teached this in my very first courses during studying chemistry. Maybe statisticians in England or wherever have another view arosen from their daily handling of errors of all kind .

Theoretical statistician. A second class mathematician who imagines that he is a first class statistician.
Applied statistician. A second class statistician who imagines that he is a first class scientist.
Medical statistician. A second class scientist without any imagination.
Guernsey McPearson's Drug Development Dictionary

❝ From the table in the GL, it’s clear that 0.760 – rather than ln(1.25)/sqrt(ln(0.3²+1)) – should be used.

Seems right, beside the fact that the differences to the 'exact' formula are only marginal (+1 in the last decimal if % is used) and should not have any practical impact.

May be the whole story is a bit hair-splitting as always with us.
The guideline does not adress at any time that k is connected to the scaling standard error s₀ or CV₀ via the well known formula you give above. Eventually they even don't know this formula . They formulate the widening via Boddy's formula exp(+k*s_WR).
In that sense they haven't defined a regulatory s₀ or CV₀ but rather a regulatory k. Thus rounding is spirited off in a magical way if we accept this view.

Take k=0.760 to make your regulator feel confident that you accept his competence to define it that . Don't forget the zero in reporting k!

BTW: The Americans are a little bit smarter or nearer to the theory in defining a s₀=0.25 and using log(1.25)/s₀ as BEL for
-BEL < (µT-µR)/sWR < BEL .
Aside from the fact that the value 0.25 is not so well chosen in leading to the already discussed discontinuity at CV=30%.
BTW2: In the literature about scABE you can find our s₀ to various degrees of precision f.i. 0.29, 0.294 or 0.2936. This in turn leads to k=0.769, 0.759 or 0.760 with 3 decimals.

❝ Should we round another two times (both the CL and the acceptance limits to two decimal places) – in analogy to Section 4.1.8?

I would do so if 0.760 is accepted.