Belarus = member of the EEU [Regulatives / Guidelines]

posted by Helmut Homepage – Vienna, Austria, 2018-01-04 14:08 (1971 d 06:44 ago) – Posting: # 18139
Views: 25,057

Hi Mikali,

❝ Due to logistic issues (a small clinical center and a highly variable drug) we have to conduct a bioequivalence study in multiple groups (two).


Are you aiming at reference-scaling for Cmax, i.e., perform the study in a replicate design? Even if not, opt for the “staggered approach” – not the “stacked” one (see above).

❝ Our competent authority requires a justification not to include the group effect in the proposed statistical model.


IMHO, stupid – but according to the GL. :-(

❝ The groups will be separated by a week at maximum.


Very good.

❝ It seems that we meet criteria set out by FDA to use a statistical model without including the group effect. Our competent authority can accept the FDA position on this issue, but we should properly reference it.


See this presentation summarizing my current thinking. Note that (since I don’t speak Russian) my remarks given on slide 16 are only partly correct. A justification in the protocol (as you rightly mentioned) should be acceptable. In the discussion following my presentation it became clear that:

❝ Thus, where can I find this information under FOI (link) …


FDA’s step-wise models (which I would never ever use) are given here and there (maybe there are some more; too lazy to google). However, in the second document you find Comment 9:

If ALL of the following criteria are met, it may not be necessary to include Group-by-Treatment in the statistical model:

  • the clinical study takes place at one site;
  • all study subjects have been recruited from the same enrollment pool;
  • all of the subjects have similar demographics;
  • all enrolled subjects are randomly assigned to treatment groups at study outset.
  • In this latter case, the appropriate statistical model would include only the factors Sequence, Period, Treatment and Subject (nested within Sequence).
Note that “the appropriate statistical model in this later case” is the conventional model for a 2×2×2 crossover.

❝ … might it be possible that someone can share a copy of letter signed by Barbara Davit where it is outlined requirements to ignore the group effect in a statistical model?


I can’t share mine (chained to my table by a CDA). Maybe Detlew can share his. Note that the wording of Barbara’s letter is identical to the second reference above.
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