Bioequivalence and Bioavailability Forum

Dear Weidson!

❝ ❝ Pilot studies are good scientific practice

❝

❝ Well, this is what many researchers still believe to be correctly.

A mathematician is a blind man
in a dark room looking for a black cat
which isn't there. (attributed to Charles Darwin)

Substitute 'A mathematician' by 'Any scientist performing a main study without prior knowledge'.

❝ […] if we do a pilot study and the high variability is found with a low N (intra-subject in the case of a crossover trial), then we have a study with little power to draw valid conclusions in respect of bioequivalence.

Well, it’s not the objective of a pilot study to demonstrate BE. I always prefer to take the uncertainty of the estimated CV into account. The smaller the pilot, the larger the penalty (i.e., the larger the main study).

❝ Recently I did a data mining in my database [...] and the pattern found was that the ratio's of Cmax and AUC is not stable for studies with underpowered.

❝ Please also do this analysis in your bank you will be surprised ...

It’s rather difficult to surprise me – I can confirm your observations.
Another reason why not to perform small pilot studies. I don’t know of any statistical method which would help us in dealing with the uncertainty of the PE besides the confidence interval itself – but that’s trivial. Therefore it's always a good idea to perform a sensitivity analysis as part of the sample size estimation (i.e., treat the PE from the pilot not as “fixed” as well).

Nothing shocks me.
I’m a scientist. (Harrison Ford as Indiana Jones)