Bioequivalence and Bioavailability Forum

Dear Hiren!

❝ But I am not geting how can we claim two formulation bioequivalent if there is significant formulation effect????

Statistically significant does not imply clinically relevant. In BE any [≥-20.00% & ≤+25.00%] difference (log-scale ±0.2231) generally^* is considered irrelevant.

❝ Just on the basis that the variability of such difference will be less (narrow CI) how can we claim BE???

Since the CI is within the acceptance range. BE is de­fined as AR_lo ≤CL_lo and CL_hi ≤AR_hi; nothing else. If we in­crease the sample size (keep­ing the CV constant) sooner or later any (!) formulation will show a statistically significant difference – if the PE ≠ 100%. Have a look at this slide: The minimum sample size according to many guidelines is 12. With T/R 0.95 and a CV of 15% we expect already a power of 83% (the CI will be 85.07 – 106.09%). With 48 sub­jects the upper CL drops below 100% and we will get a statistical significant difference (CI 90.27 – 99.98%).

Or, if we keep the sample size at 12 and our CV is even lower, the power will increase – and there­fore, also the chance to get a significant difference (exemplified by the light blue curve in the linked presentation). With a CV% of 10% power will be 98.8% and with 5% 99.99999995%.

May I ask you for the sample size in your study?

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• Except some NTIDs ([≥-10.00% & ≤+11.11%] = log-scale ±0.1054) or HVDs/HVDPs where the AR may be wider.