Bioequivalence and Bioavailability Forum

Dear All,

Apologies for opening this old thread but hope this could help me in one of my present study.

We have conducted one Pivotal BE study for NTI drug.

Study is passing in all the criteria except that upper limit of the 90% equal-tails confidence interval for σWT/σWR is coming more than 2.5.

The reason behind the same is that there is difference in intrasubejct variability between test and reference product for one of the PK parameter.

Incase we exclude one subject from the study (suspected outlier) then variability is coming almost similar for test and reference product.

For this subject there is five fold difference in PK parameter for the same treatment which is also not inline with other subject data.

Can mentioned method be used for outlier detection. Has anyone used the mentioned method for FDA dossier submission.

Apart from the above, incase pilot study is conducted in full replicate design with adequate number of subject and we want to plan Pivotal study considering the variability of test and reference product, is there any program to calculate the sample size for which upper limit of the 90% equal-tails confidence interval for σWT/σWR can be lesser than 2.5.

As such the σWT/σWR ratio won't change but f value and degree of freedom would change based on the sample size and accordingly upper limit of the 90% equal-tails confidence interval will change.

Regards
Pjs