Bioequivalence and Bioavailability Forum

Hi all,

Let's say I have a study where two products are tested against a reference (3 period, incomplete block). Test 2 product for one of the subjects is an outlier for AUC and Cmax as per protocol (>3 studentized residuals away from the mean).

The question is, should this subject be removed completely from the study or just the period in question?

From a statistical point of view, only one of the test products/periods was an outlier, however, I'm of the view that given that since we don't know what caused the "unusual" profile in the Test 2 profile, perhaps it's better to remove the subject altogether. For example, the subject might not have consumed the whole tablet in the Test 1 and ref periods and then swallowed all the pills in one go (obviously highly unlikely due to the various checks in place and the fact that the first two periods look "fine"). The subject could have fallen ill, became dehydrated, ate something, consumed a "protocol banned" product, etc. without informing staff in the previous period, but this only partly affected the results then; the effect was really only seen in the next period. You can all probably come up with other possibilities for why Test 1 and/or ref could have also been affected, even if not to the same degree.

Looking forward to reading your input.
Mac