Inflation of the TIE as well [RSABE / ABEL]

posted by Elena777 – Belarus, 2020-01-29 20:01  – Posting: # 21098
Views: 4,627

Dear Helmut,
Let me describe the situation in detail.
We recently conducted a replicative BS (EMA approach). We submitted the study to the Belarusian NCA and received comments on statistics. In the protocol, we stated that first we would try ABE, and if we failed then would go to scaling. We passed the BE criteria within 80-125% range for both Cmax and AUC (ABE approach). The expert demanded to calculate RR that we did not do but can do, but also to control TIE that we think is nonsense. As a result, I have a couple of additional questions.
  1. Is calculation RR for the reference drug mandatory and used somewhere else, except to widen the bioequivalence interval for Cmax (reference to my first questions)?
  2. Is TIE nominal and cannot be controlled if we do not widen the bioequivalence interval in replicative studies and use ABEL?
  3. Could you provide us with formula to calculate CI for fully replicative studies in math not computer format?
  4. How mathematically (in formula) can the inflation of TIE take place in RBS if we nominally control t-parameter (choose it from tables, for example)?
  5. What role of fixed or random effects in RBS or ordinary BS?

I am not a statistician
Best regards

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