Bioequivalence and Bioavailability Forum

Dear John,

❝ Can someone explain to me what the 2.5 cutoff for the Within subject (T/R) Variability Test is based on? I read the paper from FDA but it doesn't seem to provide a clear answer (at least to me).

if you mean the paper

Yiang et al.
A Bioequivalence Approach for Generic Narrow Therapeutic Index Drugs: Evaluation of the Reference-Scaled Approach and Variability Comparison Criterion
The AAPS Journal (# 2015), published online 04. April 2015
DOI: 10.1208/s12248-015-9753-5

you may find out that the value 2.5 is is based on simulations. They have done some simulations also with other cutoff values and were more or less satisfied with the influence of the variability test using 2.5 on the overall power (sABE test + pe constraint + variability test). Quote from the discussion:

"In further evaluation of the scaled + capping BE limits and variability comparison criterion, simulations indicated that the study power was mostly determined by the power of the variability comparison for BE studies with large difference in variability when the GMR is close to 1 (Fig. 5). Scheme I with δ=2.5 was selected as the recommended criterion for variability comparison because it could produce more than 80% power for similar products (0.95<GMR<1.05 and σWT/σWR<1.2) and less than 20% power for products with larger than twofold differences in within-subject standard deviation using 24 subjects".

For me that reasoning is gut-feeling or if you prefer common sense.