Bioequivalence and Bioavailability Forum

Hi ElMaestro,

❝ […] It just does not strike me as being connected to the real world in any meaningful way

❝ Quite possible it made sense to somebody. At some point. Perhaps. Or maybe not.

I think it’s crap. I heard about it in the very early 1980s, when one of our sponsors suggested to report it as “additional information”. I said that’s rather “subtractive information” but he insisted. Life at a CRO is hard. A quote from the paper:*

This author's experience with bioequivalence trials suggests that most clinicians tend to make their equivalence statements in a symmetrical manner, stating, for example, that if the absolute (or possibly proportional) difference between µ_n and µ_s, is less than some spe­cified value, then N is therapeutically equivalent to S and if not, doubt as to therapeutic equi­va­lence exists.

❝ I wonder what the figures will look like for a drug which proves to be BE but with 1.00 not part of the conventional 90% CI?

I don’t understand. This is exactly my example above (BE, but 1 not within the conventional CI). Can you help my little brain?
Our 2,2,2 reference data sets in Phoenix/WinNonlin 6.3 (dropped in v6.4):

        90% CI        WL’s 90% CI  
A   90.76 –  99.62   91.76 – 108.24
B   51.45 –  98.26   55.45 – 144.55
C   39.41 –  87.03   43.32 – 156.68
D   51.45 –  98.26   55.45 – 144.55
E   55.71 – 151.37   53.52 – 146.48
F   93.37 – 106.86   93.26 – 106.74
G   88.46 –  95.99   89.26 – 110.74
H   86.81 – 100.55   88.27 – 111.77

BTW, sometimes it is not possible to compute WL’s CI (see the paper).

---

• Westlake WJ. Symmetrical Confidence Intervals for Bioequivalence Trials. Biometrics. 1976;32(4):741–4. doi:10.2307/2529259.