BE study designs [Design Issues]

posted by Helmut Homepage – Vienna, Austria, 2006-01-16 16:39 (6525 d 14:10 ago) – Posting: # 54
Views: 25,501

Dear Essar,

in order to continue with the nomenclature generally used in BE studies I have re-aranged your table. Periods (P1-P3) in columns, and Sequences/Groups (S1-S3) in rows:
│    │ P1  P2  P3 │
│ S1 │ T1  T2  R  │
│ S2 │ T2  R   T1 │
│ S3 │ 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"?

Question #1: no
Question #2: yes

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

Yes, explanations following:
Your design is not balanced in respect to all effects in the model, in other words, 3 combinations of treatments are missing. The chance of regulatory acceptance of a 3×3 is close to zero.
The plainest design you may apply is a Williams' design (3-treatment, 3-period, 6-sequence):
│    │ P1  P2  P3 │
│ S1 │ T1  T2  R  │
│ S2 │ T2  R   T1 │
│ S3 │ R   T1  T2 │
│ S4 │ T1  R   T2 │
│ S5 │ T2  T1  R  │
│ S6 │ R   T2  T1 │

If you want to extract paired comparisons (e.g., for the nonparametric method) you will fail with your design (3×3), but succeed with the given one (6×3).

Since we are leaving the novice's level now, I would suggest you some further reading (not cheap, but every cent worth):

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

Have a look at

Sample Size and Power Calculation for High Order Crossover Design
Bio/Pharma Quarterly 9(1), 9-14 (March 2003)
which is available online (277kB PDF).

Good Luck!

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