## BE study designs [Design Issues]

❝ The most simple cross-over design is the 2×2×2 (2 treatment, 2 period, 2 sequence):

❝ Half of the subjects are treated in the first period with test, the other half with reference; in the second period the first half is treated with reference, and the second half with test.

❝ Therefore we have two sequences (or groups): T-R for the first half of subjects, and R-T for the second half.

Dear Helmut,
Taking your explanations ahead, I have tried to prepare a study design for a three treatment BE study, i.e., a BE study comparing:
1. Two formulations of a generic product T1 and T1, and
2. A reference product, R.
The aim of the above study is:
To evaluate, which of the two formulations (T1 or T2), prepared by a generic company is close to the reference product R, in a single BE-study

So, first one-third of the patients (Gp A) are treated in the first period with Test T1, the next one-third (Gp B) with Test T2 and the last one-third with Reference R (Gp C).

In period 2, first one-third of the patients (Gp A) are treated in the first period with Test T2, the next one-third (Gp B) with Reference R and the last one-third with Test T1 (Gp C).

In Period 3, first one-third of the patients (Gp A) are treated in the first period with Reference R, the next one-third with (Gp B) Test T1 and the last one-third with Test T2 (Gp C).

The above periods are summarized in the table below:

Group A B C
Period 1 T1 T2 R
Period 2 T2 R T1
Period 3 R T1 T2

Now, please let me know whether my design is right? Is it approprirate to name this study as "3-treatment, 3-period, 3-sequence crossover Bioequivalence study"?

Can there be other designs to compare T1 and T2 with R in a single BE study?

Also, please let me know how you calculate the no of subjects required for this type of a study.

Regards,
Essar