Bioequivalence and Bioavailability Forum

Dear Lukamar,

❝ ❝ And it is very difficult to guarantee (IMHO it's not possible at all) that clinical and statistical team will not have access to bioanalytical data once bioanalysis has started.

I guess, one can "guarantee" the separation of data and information flow in terms of audited and well controlled processes - at least, in a way which may comparable to e.g. handling randomisation lists.
Even most accurate processes can never totally exclude criminal energy.
But I won't tend to a priori assess bioanalytical centers as being less trustworthy than randomisation units, pharmacies / trial supply units etc. who deal with randomisation lists … .

In many pivotal Phase III studies one has to establish processes of separation of data and information flow which seem to be even more critical and complex to "guarantee".
Let's think of unblinded Safety Monitoring Boards, unblinded interim evaluations even of primary efficacy (third party, independent statistician, and corresponding boards)... or settings in which one may need to control how to separate the data flow for parameters that have unblinding potential (e.g. if a test product modifies liver values in another way than the comparator, you need to separate the liver values from the data flow …).

Let's think not at least about a situation in which non-inferiority might be the primary hypothesis in such a pivotal Phase III setting (where per protocol is the primary set and exclusion of subjects from the PP set can heavily affect the primary outcome).

Just wish to say: at least the principle of separating data and information flow via accurate processes seems to be well accepted (even by authorities) also in settings which are even more critical amd more complex to control.

The question is: Will regulatory reviewers assess us, while working on BE settings, as less trustworthy than acting in pivotal Phase III settings?

To avoid this, I think, we can only contribute by being as transparent as possible (analyzing all samples also for excluded subjects etc.) when working on BE studies.

Many thanks and best regards,

Dirk