Bioequivalence and Bioavailability Forum

Hi Tushar,

❝ For Sample size calculation, we normally select higher intra CV of primary parameter (Cmax or AUC).

Correct.

❝ Our IEC ask for scientific justification (literature) for why to choose higher Intra CV parameter for sample size calculation only.

Literature? That’s trivial. Remind/teach your IEC that we have to demonstrate BE for both AUC and C_max. Given their acceptance ranges are the same, naturally the PK metric with higher CV_intra will dictate the sample size of the study. In most cases we can expect C_max to be the “leading” metric. If scaling is allowed only for C_max (EMA), it might be different.
Example (full replicate RTRT|TRTR, T/R 0.90, 90% power):

      CV%   n
AUC   30   54 ← higher sample size due to conventional AR
Cmax  45   40 ← lower sample size due to scaling / widening of AR

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Edit: If the IEC insists in written stuff, show them the “VICH GL52 on Bioequivalence” Section H:

Sample size for a BE study should be based upon the number of subjects needed to achieve BE for the PK parameter anticipated to have the greatest magnitude of variability and/or difference in treatment means (e.g., C_max).