Bioequivalence and Bioavailability Forum

Dear Dan and Helmut,

many thanks for your posts.

Regarding bioanalysis of samples, we tend to agree to Helmut.

We use to analyze all samples (maybe exceptions only in very clear cases; e. g. an early drop-out in period 1 of a 2*2 design).
We feel this is in line with EMA statements (e.g. the statement within the comments to the Draft EMA guideline; also cited in the EGA Symposium document):

All samples should be bio-analysed. This is useful if there is disagreement between Member States over an exclusion as it enables the statistical analysis to be repeated.

We wish to be as transparent as possible and will, in borderline cases, not dread sensitivity analyses.
We just do not wish to be punished for this approach of transparency (which is even supported by Option 1) by receiving negative regulatory feedback on option 1 just from the formal reason "date of start of bioanalytical assessments too early" although option 1 does not take any misuse from this circumstance.

Dan, I agree to the conduct of a Data Review Meeting to fix the allocation of analysis sets. We always do this, irrespective of applying option 1 or 2.

However, we prefer to perform this on data which is at least sufficiently clean and validated. Everybody who is long enough in this business knows that e.g. the probability of disagreements between Medical Monitors and Investigators on relationship of AEs will be higher than the corresponding AE incidence .
I.e. if you fix the exclusion of subjects before the sponsor's Medical Monitors have seen all the relevant cleaned data, this may lead into trouble. If you wait until clean data can be used as a base (which we prefer) then you will be in the situation I mentioned: i.e., option 2 will not allow starting the bioanalytical assessment more or less prior to DB lock.

Thanks a lot and best regards,

Dirk

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Edit: Document linked. [Helmut]