Elite Pharmaceuticals Inc (ELTP)

[WeeZuhl]

Kayak, great post. You sound like a PharmD!

ELI-202’s Second Pivotal BE

I’ve been hoping someone would explain how the first pivotal could not meet expectations, but how a followup pilot could determine that the next pivotal would pass with flying colors (as NH indicated)...

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I believe the 9/9/2014 PR directly addresses this concern with the statement “Two formulations were dosed in the pilot study and both formulations demonstrated that a repeat bioequivalence study with 32 subjects or more would be expected to be bioequivalent for the measured parameters.”

I think the best explanation for why an additional study with 32 more subjects would be expected to show bioequivalence is based on the concept of statistical "power."


http://en.wikipedia.org/wiki/Statistical_power

The power of a test sometimes, less formally, refers to the probability of rejecting the null when it is not correct... As the power increases, there are decreasing chances of a Type II error (false negative)...

Power analysis can be used to calculate the minimum sample size required so that one can be reasonably likely to detect an effect of a given size. Power analysis can also be used to calculate the minimum effect size that is likely to be detected in a study using a given sample size...

The sample size determines the amount of sampling error inherent in a test result. Other things being equal, effects are harder to detect in smaller samples. Increasing sample size is often the easiest way to boost the statistical power of a test.

In summary, Nasrat's argument is that the failure to show bioequivalence is a false negative because of a sampling error (too small sample size). He used power analysis to determine that an additional 32 subjects would increase the statistical power of the study enough to overcome the false negative (Type II error) and prove bioequivalence. Nothing was changed except adding 32 more subjects to the data set. (Although I suspect he added a few extras just to be sure, as each additional subject further increases the power of the study and decreases the probability of a false negative result.)