Bioequivalence and Bioavailability Forum

Dear Andrew!

❝ A regulatory authority has asked some questions about a BE study my client performed back in the 1990s.

Which one? Answer might depend… Sometimes it’s useful to have a look at guidelines being in force at the time of performing the study.

❝ In particular, they have asked that: “From the ANOVA tables, influence of treatment, period and subjects (subjects within sequence & sequence) effects should be submitted and discussed by the applicant”.

Oh no! They were asking for treatment and period effects as well!

❝ I have had a look at these and see that for all primary parameters, the P values for treatment, period and sequence are non-significant (>0.05). However, again for all primary parameters, the P values for subject (sequence) are highly significant.

Hhm. Sequence? I would expect to see only subject(sequence) in the tables.

❝ Can you tell me what, if anything, this might mean?

Chance? In a large metastudy^* significant effects were found in about ~10% of 2×2 studies (n=324), and ~5% of 6×3 studies (n=96). In other words you can expect a significant effect at the level of the test – which makes a true sequence effect (= unequal carry-over) unlikely in properly performed cross-over studies.

❝ [… ] you will need to confine yourself to words of one or two syllables only!

Well, in your post you used multisyllabic words as well. The last time we met you were quite fluent…

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• D’Angelo G, Potvin D, Turgeon J. Carry-Over Effects in Bioequivalence Studies. J Biopharm Stat. 2001;11:35–43.