Ahem – number of units? [Dissolution / BCS / IVIVC]

posted by ElMaestro  – Belgium?, 2019-10-06 22:45  – Posting: # 20671
Views: 1,641

Hi Hötzi,

» Sure. The problem is the ‘regulatory crep’ I suspected in my post. Jiři showed nice simulations about the false positive rate. To squeeze the lower CL ≥50 is not another league but another sport. How many units will we have to test in the future? 24, 48, 96?

Am thinking loud here: You can bootstrap a principal answer to such questions as well.
You generate a dissolution dataset with n chambers for T and R; then you resample with replacement to generate datasets with m chambers (m > n, presumably) per product, to find out at which level of m you get an f2 limit >50.

This is quite simple, actually, to do the programming and simulation. But yes, if you end up with 326 chambers per product then I guess you are royally screwed.

We could do a publication about this. We'd need a candidate dataset, I don't think I have one for this which I could put into the public domain.

Could this even be done as a two-stage approach? You first look at bootstrap f2 levels in the initial n-chamber scenario. If you are passing, stop. Else, find your sample size m and run the (m-n) chambers on top, then re-bootstrap the whole thing. This would be a "two-treatment, m-chamber, tripple bootstrap, two-stage dissolution trial", and you may need to work with increased coverage intervals for alpha preservation.

Man, I should win a Nobel prize for this idea.:-D

I could be wrong, but...

Best regards,

"Pass or fail" (D. Potvin et al., 2008)

Complete thread:

 Admin contact
20,794 posts in 4,354 threads, 1,446 registered users;
online 6 (0 registered, 6 guests [including 4 identified bots]).
Forum time: 05:50 CEST (Europe/Vienna)

I’m not a pessimist,
I’m just a well informed optimist.    José Saramago

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz