Bioequivalence and Bioavailability Forum

Hi everybody.

I' like to share with all of you one doubt that I have regarding ANVISA's point of view on triangulation points. I don't even know if that concept is known by you guys, but a triangulation point is a null point (concentration <LLOQ) between two non-null points. ANVISA's staff understand that this is a point that makes no sense and even if it was reanalysed by the lab it should be deleted to make a interpolation between the non-null points. Keep in mind that we could have lots of triangulation points in sequence. I do not agree with that, in fact I find it difficult to agree with data disconsideration at all. If the data is available and you are certain of its veracity, then it should be included in PK derivation.
In light of a new BE study that almost was approved when these points were excluded and clearly not approved when not excluded I would like to know, since I'm no expert in EMA and FDA regulations, if anywhere else this is a standard procedure.
When we exclude points like those with the intention of eliminating a bias, we may be in fact creating another (big) one and we'll never know for sure. How would we know if the point that was excluded was wrong and not the ones surrounding it? That exclusion can cause a massive difference in AUC, changing even the study's conclusion in some cases.

What do you think of that procedure?

Tks in advance.

Lucas