Rivastigmine Transdermal Patch [General Sta­tis­tics]

posted by Lucas – Brazil, 2014-07-31 00:24 (3528 d 10:01 ago) – Posting: # 13320
Views: 11,560

Hello dear colleagues.

We are planning a BE study of a transdermal patch of Rivastigmine. This pharmaceutical form requires additional performance analysis, according to the FDA draft guidance published in 2010. The additional studies are: “Adhesion analysis” and a “Skin Irritation and Sensitization study”.
The adhesion is measured in scores - 0 = ≥ 90% adhered; 1 = ≥ 75% to <90% adhered; 2 = ≥ 50% to < 75% adhered; 3 = > 0% to < 50%; and 4 = 0% adhered – at different time points (i.e. 6, 12 and 24 hours after attachment of the patch).
FDA requires a comparison between the scores of test and reference treatments (page 2): “The adhesion evaluation of the active test product and RLD must demonstrate that the upper bound of the one-sided 95% CI of the mean adhesion score for the test product minus 1.25 times the mean adhesion score for the RLD must be less than or equal to 0.” And also states (page 3): “The proportion of subjects with a meaningful degree of detachment should be no higher for the test product than for the RLD, and de­tach­ment should not occur earlier in the application period for the test than for the RLD.”
Let’s leave the Skin Irritation and Sensitization study aside for now. Any of u guys have experience with this kind of statistical analysis? Since the variable is a score, we do not know what would be a plausible test to be applied for the calculation of the CI. Also, how would one demonstrate what is asked in the phrase described above (of page 3)? Is it a non-superiority analysis? If so, how would that be?
The study is for submission in ANVISA, which does not have guidelines on that, and seems to be more willing to use FDA’s guidance as their reference.

Complete thread:

UA Flag
Activity
 Admin contact
22,957 posts in 4,819 threads, 1,640 registered users;
57 visitors (0 registered, 57 guests [including 7 identified bots]).
Forum time: 09:25 CET (Europe/Vienna)

Nothing shows a lack of mathematical education more
than an overly precise calculation.    Carl Friedrich Gauß

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5