Bioequivalence and Bioavailability Forum

Dear ElMaestro!

❝ What is an outlier?

❝ To me, an outlier is a point whose presence cannot credibly be

❝ accounted for by random scatter or natural variation, but whose presence

❝ has another and identified explanation.

Agree.

❝ To me, an outlier is not just a point that somehow looks, smells and feels

❝ different from the other points.

Agree. That’s why I called for statistics. Nice to sit here in Brussels – the beer looks, smells and tastes different from Vienna’s. No statistics needed here (not outliers, but a different sample).

❝ I am not a big fan of the practice of running some sort of outlier

❝ detection test and then, solely on basis of statistics, deeming this or

❝ that point an outlier.

Did I say that? I said first you have to know that there is one – based on some objective method of detection – and then look for a cause.

❝ Do slow metabolisers cause outliers, if their phenotype occurs in say 0.1%

❝ of the population? No, because the data points they cause represent natural

❝ but rare variation.

Sure. There’s even a term for that type of outlier: concordant outlier – nothing to worry about in BE, but may be of interest (see the end of this post for a surprising example).

❝ Here and there one can observe the odd data point space that is just not a

❝ credible (credible in this sentence is not quantitative) representation of

❝ a model …

Yes. That’s a discordant outlier. Affects BE. All the reasons I have given in my last post may be applicable…

❝ … and some scatter and where there really is no identified source of

❝ the issue.

… or the mysterious S × F interaction.

❝ That's not an outright outlier, but a matter for an auditor or inspector

❝ to look into, and it should in my opinion remain so unless a plausible

❝ reason can be identified.

Again: You have to be suspicious first in order to start a search. I would prefer to base my strategy on a pre-defined method rather than saying: Oops, looks, smells and feels strange…