Bioequivalence and Bioavailability Forum

Dear Byung-Ju,

seems that you have a high budget. That’s nice and decreases your changes of failure (producer’s risk β = 1 – power).
But: Most guidelines suggest a power of 80–90%; you may run into problems with the Ethics Committee. It’s the job of the EC to judge the risk of subjects (drug effects, common risks due to repetitive venipuncture, AEs, etc.) and the advantage for the health system (cheaper drugs). It’s not the job of the EC to decrease the risk of failure of a pharmaceutical company, which is commonly 10–20%. You can give it a try with 95% power (if you expect a high drop-out rate), but I don’t think that any EC will accept 99% power (more than doubling the sample size from 80% power; example below for T/R 0.95):

            CV%
power│ 15  20  25  30
─────┼───────────────
 80  │ 12  20  28  40
 90  │ 16  26  38  52
 95  │ 18  32  46  66
 99  │ 26  44  68  94

There’s another pitfall. Did you ever come across the term ‘forced bioequivalence’? The sponsor suspects that the test will deviate a lot from the reference but will not present a sample size estimation based on that. Instead a sample size estimation with high power for a better (though not realistic) value is presented. Example:

∆ 11% (T/R 89%), n=44, 79.9% power (realistic; not presented)
∆  5% (T/R 95%), n=44, 99.1% power (presented)

Regulators might not like that. Quote:

We are interested in public health –
not in the profit of the pharmaceutical industry.