Bioequivalence and Bioavailability Forum

Hi Lechia,

❝ There are even arguments that it is not ethical to run a pivotal study if the pilot shows equivalence, i.e. why subject more healthy volunteers to a drug if not needed?

Yes. In Europe we had a north-south slope. Scandinavian countries and Germany were generall happy with this idea. From Spain the response sometimes was along these lines:

“Thank you for showing the CI to be within the acceptance range. Now submit a properly designed pivotal study.”

Strictly speaking this request is correct. BE should be demonstrated in a reasonably powered pivotal study, whereas a pilot study is exploratory by nature. Generally the GMR and CV are only “guess­ti­mates” and the power low.
Which agency are you targeting?

❝ […] Do we need to put any additional text that mentions that if BE criteria are fulfilled no pivotal study will be conducted?

Exactly.

❝ Secondly, is this not in effect cheating? […]

Maybe. Maybe not. The type I error might be inflated. Consider a recent paper* and download the 16 (!) electronic supplementary PDFs. If you have questions, I guess ElMaestro will be happy to give explanations.

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• Fuglsang A. Pilot and Repeat Trials as Development Tools Associated with Demonstration of Bioequivalence. AAPS J (Epub 3 March 2015) doi 10.1208/s12248-015-9744-6