Bioequivalence and Bioavailability Forum

Hi Astea,

❝ It is our first study with failed BE …

Sorry to say but I will not be the last one.

❝ … and I anticipate the sponsor's anger.

Tell the sponsor that 10–20% of properly designed and performed studies fail by pure chance. That’s part of the game.

❝ I have no ideas of what to do: the standardized differences don't afford to exclude subjects.

Sure. I suggested just an additional evaluation. Of course in Russia it is difficult. According to the old guideline you have to switch from the primary metric AUC_t to AUC_∞ if 80% are not covered. The “Red Book” follows the EMA’ GL.

❝ Another serious problem is inadequate design: we have only 4-5 non-zero points for each subject; […]

That’s really bad. I guess your LLOQ was way too high…

❝ For our case "after a very long, long time" is just about half an hour!

I was talking about true zero, not BLQ.

❝ (We've got curves similarily to those pointed in the article Upadhyaya V., et al. …

That’s a strange paper. In Fig. 6 they have not a time-scale, but clicked the wrong button in Excel. That’s a line-plot. Bizarre. The T/R-ratios are close to 1 and the reported CVs were 5.17–6.34%. However, I calculate 13.1–18.4%.
They succeeded in selling the sponsor an extremely overpowered BE-study in 72 subjects with 5,328 plasma samples. Are Indian IECs sleeping or waving all studies through – completely misunderstanding what their job is?
“Furthermore, there was no adverse event during the course of the study.” Not even a single case of headache? Gimme a break.

❝ All the patients have second peak in the profile of the curve and this peak is significally smaller than the first.

Good to know that the second one was smaller.

❝ Thank you for the link but full text of the article is not available.

You’ve got .

❝ But you claim that PK model is not necessary for standard BE study, am I right?

PK modeling is not acceptable in BE (only NCA), but it helps to understand what’s going on.

❝ Are there any official documents…

I don’t think so.