## New guidance on Sta­tis­tical Approaches to Establishing Bio­equi­va­lence [BE/BA News]

Dear All

The FDA Generic Drugs Advisory Committee recommended in 1991 that the primary comparison of interest in a BE study is the ratio, rather than the difference, between average PK parameter data from the T and R formulations. Using logarithmic transformation, the general linear statistical model employed in the analysis of BE data allows inferences about the difference between the two means on the log scale, which can then be retransformed into inferences about the ratio of the two averages (geometric means) on the original scale. Logarithmic transformation thus achieves a general comparison based on the ratio rather than the differences.

Under lognormal data for PK paramertes ratio of geometric means the same as ratio of medians

However, situations with different within-subject variances of drugs may often occur in practice. BE tests cannot be easily transformed back from the log scale to the original scale under unequal within-subject variances.