Bioequivalence and Bioavailability Forum

Dear sdu!

❝ I have few questions

You are welcome. But eventually I'm not the one to answer all your questions. But lets try.

Ad 1.

❝ How do you calculate the s_int?

As I said in my post above, I don't really understand what is meant with that s_int. But this may not be necessary to know because what we really need is SE, the standard error of the (log) difference. Each statistical package I know off will give this. Then you can proceed with the above shortly outlined Al Gore rhythm.
See here for a recent comprehensive paper on SABE issues. Maybe it helps (at least in producing new questions ).

Ad 2.

❝ If above statement is correct do we assume sig_wt is equal to sig_wr ...

I would not suggest this. As far as I understand the FDA, the assumption of equal variabilities between Test and Reference should be avoided if possible (even in the case of parallel group studies!).
I must confess that I don't know the Ekbohm and Melander paper in detail. But if they talk about subject-by-formulation interaction they definitely talk about different variabilities between Test and Reference, at least between subject variabilities.

Moreover a separate within variability for the Test formulation is not identifiable in the design suggested by Haidar et. al. for evaluating reference scaled average, namely a design with the sequences RTR, RRT and TRR, the so called partial replicate design.
See this thread.

Ad 3.

❝ It was my understanding that Reference scaled Average BE is the special case of the IBE where we assume sig_D is negligible and the ...

This is also my understanding ...

❝ ... sig_wt is equal or smaller than the sig_wr.

... but the second condition is not necessarily implied.
May be the sig_wt comes out as greater then sig_wr in a replicate design which allows for estimates of both.

Since you are posting from USA (at least the forum system tells it ), can you eventually contact FDA's people dealing with SABE and enlighten us how they do all the stuff?