Bioequivalence and Bioavailability Forum

Dear Yung-yin

❝ [...] Usually, we talk about 90% CIs in data analysis of a BE study, but we do not mention what 90% CIs we calculate.

This is partly due to the fact that we implicitly assume that we talk about classical confidence intervals and therefore there is no need to mention the sort of variation by their name.

❝ to add various 90% confidence interval (CI) calculations into bear for R.

❝ My questions are: (1) is it necessary to do so? regulatory or statistical basis? and (2) if yes, what 90% CIs will you recommend (Anderson-Hauck's, Westlake's, Locke' exact CI, Fixed Fieller's, Mandallaz-Mau's, etc.)?

As always it depends. On the purpose which bear shall be used for.

Is it a tool for evaluation of ABE studies which have to be submitted to regulatory authorities?
Then my recommendation is:
(1) It is not necessary to implement some sort of other CI's.
To borrow a sentence of Helmut (I hope with his permission): There can only be one!

Imagine some variants of other CIs implemented and all used and submitted by "naive" users (and, without bothering someone personally, there are such out there, too on this forum ).
  Method1 -> bioequivalent
  Method2 -> not bioequivalent
  Method3 -> bioequivalent
and so on. What do you think about regulator's view of that?
Especially if they take five minutes as ElMaestro mentioned. Although I think the right time span is in mathematically notation < 5 min .

Since the standard method is the classical CI, leave it as is.
If mentioned at all guidelines recommend this approach.

There is one exception: If you are not willing to assume a log-normal distribution for a specific pharmacokinetic target but rather a normal distribution (and this can be a reasonable strategy for such metrics as HVD, Swing, PTF or others), but need the CI for the ratio, the Locke/Fieller CI for the untransformed values may be helpful.
But I have not seen many cases where such PK metrics are used as primary targets with the need of calculating a CI as BE test.

But if bear is a tool for academic interest, implement other CIs for educational purposes. Most of your mentioned variants under (2) of your question are historical milestones in BE testing and certainly have interest in education. Which to implement you, as university staff, know better then I.