Bioequivalence and Bioavailability Forum

Dear Boonchai_L,

that's an excellent post, and certainly worthy of some thoughts. From a practical perspective, I think real life is often rather cruel.

When a sponsor calculates the sample size for a BE study, literature is a good starting point. Yet a lot of sponsors are seeing their studies failing because they are not realistic about the CV's. I don't think the solution is just pooling or any other statistical approach. In stead, I think a (but not necessarily the [only]) solution is get real about CV that can be produced. It is often virtually impossible to tell if a CRO is capable of getting the CV as low as you hope, especially if the CRO does not indicate they have worked with the API in question before. The analytical method may differ, the practices at the clinical facility differ etc.
Unless the sponser has a good reason to believe the actual CV will be in the low end of the published CV's I think the expectation should be in the high end of the published CV's.

Here's a well kept secret: Audits (not just the ordinary motherhood-and-applepie-system-audits) are a sponsor's best friend in this regard.

S.