Bioequivalence and Bioavailability Forum

Hi Mittyri,

that’s a great post!

❝ The investigator insists that if the volunteer has no clinical signs (no com­plaints) - there's no AE.

❝ I think this position is a little bit strange. For example, if control lab test indicates that WBC level is 3.6 and the volunteer has no complaints, Investigator concludes - NCS! No AE!

❝ I think in this case AE should be reported.

Fully ACK. I’m not sure whether it is already an AE, but most protocols would require at least a follow-up lab exam.

❝ But where is a borderline??

Very good question. Invest the intellectual horsepower in the protocol. I think the PI does the reli­ability of the study’s procedures no good if he/she checks as many as possible lab deviations “NCS” and has the ambition to report as few as possible AEs. I’m always a little bit suspicious if I read a report with a very limited numbers of AEs. In many countries most people are habitual con­sumers of coffee/tea – which is prohibited in many studies. Caffeine-withdrawal leads to head­aches in up to 30% of subjects… No AEs in the report? I doubt it.

❝ I've found a nice article from Michel Sibille et al. about AE definitions in healthy volunteers in phase 1.

Nice article. THX.

❝ Is that applicable for BEQ study?

With some adaptations it is a good starting point. However – unlike in FIM – the AE-profile is already known; this would allow to adapt the “warning levels”.

❝ What is your experience in AE definitions?

Case-by-case – mainly led by the SmPC of the reference product and the IMPD.