Bioequivalence and Bioavailability Forum

Dear HS,

I think you answered a question I did not ask, and I guess that comes down to my lack of language skills. But it stil remains very interesting, if I try to think along your lines.

❝ ❝ In this situation, who runs the risk, the sponsor or the patient?

❝ Both, if the interference is present in only one occasion.

One occasion, do you mean in one period? Or do you mean in one patient, both periods?

❝ Since CV_intra will be higher, the sponsor; but imagine this situation:

❝ the study was powered enough to still show BE and the undetected

❝ interference shifted the T/R towards 1, then it's only the patient's risk

❝ (without 'help' from the interference the product would not be BE)...

It sounds to me like this does not require the interference to be present in just one period, cf above. The example partially illustrates my previous point .

❝ That's why we have to check for (lack of) interferences in bioanalytics.

Or.... it could be a very good reason to think more seriously about period effects. It could come down to interference; for example, naïve patients are known to be more susceptible to distress and require NSAIDS in the first period of a multiperiod study (or the first days of a multi-day study). This phenomenon will increase interference in period 1.

❝ Randomization does not protect us if the interference occur in one

❝ occasion only. And generally they will (...blah blah followed by some

❝ gynecholophystic considerations).

Can the term 'generally' in this context be qualified in some way? Could you rephrase the paragraph? I lost it around here, sorry. I agree with the facts about hormones and contraceptives but I am not sure I understand your point.

Best regards
EM.