Bioequivalence and Bioavailability Forum

Dear Dr. Pravin!

❝ I am conducting one study of highly variable drug for EU, i have defineed the range for the BE limit is 80 to 125 % for that drug.

Assuming a conventional 2×2 design: nice, so your study is planned for completion of 40+ subjects

❝ The problem is that i have completed the one period of that study, now i want to change the BE criteria,...

Why?
Based on which new information...
How?
Widening of the interval is almost impossible according to the Questions & Answers Document; the Concept Paper for HVDs/HVDPs is expected to be implemented in July 2007(!)

❝ ...so what is more fesible, protocol deviation or protocol amendment?

Oh, I think you are in deep trouble. If you change the acceptance range, the sample size needed to demonstrate BE also changes.
You cannot simply change the design of a study and just report a 'protocol violation'.
Therefore according to EU regulations an amendment must be prepared which would be rated as 'substantial', and approval from both the IEC and the regulatory body must be obtained.
Even if you want to change your design from a simple 2×2 design to a replicated design, it will be difficult to randomize the 'extra' periods.
Whatever your washout period is, it will be impossible to get the necesarry paperwork to be done in time.

You should think it over again, and/or provide us with more informations (especially your reasons).

P.S.: Instructions.htm#Plt, please!