Rivastigmine Transdermal Patch [General Statistics]
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 This pharmaceutical form requires additional performance analysis, according to the FDA draft guidance published in 2010.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.
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 This pharmaceutical form requires additional performance analysis, according to the FDA draft guidance published in 2010.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:
- Rivastigmine Transdermal PatchLucas 2014-07-30 22:24 [General Statistics]
- Rivastigmine Transdermal Patch ElMaestro 2014-07-30 23:57
- Rivastigmine Transdermal Patch Lucas 2014-07-31 14:00
- Rivastigmine Transdermal Patch ElMaestro 2014-07-31 19:22
- Rivastigmine Transdermal Patch Lucas 2014-07-31 20:54
- Rivastigmine Transdermal Patch lechia 2014-10-07 19:26
- Rivastigmine Transdermal Patch Lucas 2014-07-31 20:54
- Rivastigmine Transdermal Patch ElMaestro 2014-07-31 19:22
- Rivastigmine Transdermal Patch Lucas 2014-07-31 14:00
- Rivastigmine Transdermal Patch Lucas 2015-02-23 17:53
- Rivastigmine Transdermal Patch ElMaestro 2014-07-30 23:57