Bioequivalence and Bioavailability Forum

Dear d_labes,

❝ And if it happens (low chance) then answer "Due to the identical protocol,

❝ due to the identical handling of blood samples, central assay of the blood

❝ samples, blah, blah ... no influence of the different centers was expected

❝ at all."?

How about:
"In order to address the concern of the assessor, it is necessary to consider how center as a factor may affect the conclusion of bioequivalence. The conclusion about BE is based on the T/R point estimate and the intra-subject variability (ln(T)-ln(R) and variability of it); if the decision of BE hinges on center performance in a manner that is unfavourable to the patient then it implies
- one or more centres affecting the intrasubject variability negatively
and/or
- one or more centres resulting in flawed estimation of the T/R point estimate.
This effectively translates into presence of a treatment by center interaction, for example that the performance of T is truly constant across centers while the performance of R truly varies across centers (or vice versa and et cetera).
It is dfficult to see how the two factors could interact, especially because the production of a formulation in a time and space that is separate from the centre. Differential handling ability among the centres cannot be ruled out (*), but this would increase the intra-subject variability (sponsor's risk) but would not affect the patient's risk. Center is therefore not considered a concern for the evaluation of bioequivalence."
Or something like that ...


EM.


(*): The study nurse at centre X had rheumatism and could not open the bottles of T because the caps were screwed too tight while she handled the bottles of R just as well as the nurse at the other center (who was not rheumatic) handled both the T bottles and the and R bottles. Obviously lacking T tablets at centre X, the nurse decided to give the subjects aspirin in stead????? Yeah right, this treatment by centre interaction thing sounds really realistic.