Bioequivalence and Bioavailability Forum

Hi VSL,

❝ 1. Study is passed in CI but mean T/R ratio is not within the 0.80-1.25.

ElMaestro’s answer is correct – if the acceptance range (AR) is 0.8–1.25 (unscaled ABE). If you applied reference-scaling (in FDA’s or EMA’s flavor) such a result is possible indeed, especially if:

• CV_WR ≫ CV_WT.
  
• Large “true” deviation of T from R.
  
• … or both.

The modified acceptance range depends only on the variability of the reference. If the test’s variability is comparatively small, the CI might be relatively narrow. That would mean a formulation could pass with a GMR far away from 1 (even <0.8 or >1.25). Statistically that would still make sense, but for political reasons the restriction of the PE of 0.8–1.25 was introduced. Actually for CV_WR ≥50% the scaled AR (and the CI inclusion rule) is of little importance at all. It is mostly the PE which counts. Tons of papers.

In the future please give complete information (acceptance range, CI, CVs, regulatory agency).

❝ 2. Study is passed in CI but there is significant p-value for treatment/period/sequence

❝ Shall we submit the study to regulatory agencies?

Ahem – did your read the guidelines?