Bioequivalence and Bioavailability Forum

Dear pash413,

in the absence of guidance covering your question, the following is my immediate reflection over your question. I am sure someone on this forum has a more qualified opinion than mine.

Month significant as a factor: Many diseases vary in severity over the year. Seasonal variations in fed status and body weight/plasma volume. Drug products degrade with time. You may do an audit, but this is very difficult in practice, because multiple centers are involved. It means the auditor would need to go to each center and dig out the subjects from the outlying month (possibly compare with subjects from 'normal' months, too).

Center significant as a factor: This is worse. Here I would dig into the data and compare group baselines of sex, body weight, biochemistry and what other info you have available across the centers. Depending on the how the data look, do an audit. If a center has been fiddling, taking it out is justified. To cover all bases, make sure such an unlikely event is per protocol.