Bioequivalence and Bioavailability Forum

Hi PharmCat,

❝ But when CI dynamically changing I think there is no good definition for TIE.

I guess you mean that the acceptance range changes (depending on the \(s_{wR}\)). The CI is not affected.

❝ For fixed CI TIE means that real GMR may be outside permissible range with this chance.

Yep. For fixed limits the TIE is defined based on the Null of bioinquivalence. Directly accessible as the power for GMR exactly at one of the limits.

library(PowerTOST)
CV     <- 0.3
n      <- 34
design <- "2x2x4"
GMR    <- 1.25
# exact
power.TOST(CV = CV, n = n, theta0 = GMR, design = design)
# [1] 0.05
# simulations
power.TOST.sim(CV = CV, n = n, theta0 = GMR, design = design, nsims = 1e6)
# [1] 0.050097

You can plug in any CV, n, design and the TIE will never exceed nominal α.

❝ Very touching assumption to consider that TIE for RSABE is a chance when GMR outside 0.8-1.25 and with this comprehension make CI range wider. Really in this situation TIE not the same as in fixed case.

Here the trouble starts (see what I wrote above). What we are doing here is actually HARKing (Hypothesizing After the Results are Known). Not exactly but we definitely generate the Null from the data. Apart from the TIE-issues every product approved by RSABE/ABEL followed its own rules. From a consumer’s perspective this is not fortunate.

❝ But people want to make ABE for high-variable drug and try to do this it's like attempt to trick statistics...

Not sure what you mean here. Can you elaborate?