Bioequivalence and Bioavailability Forum

Dear DIXIT,

This was the first introduction a member of the forum (I do not know the name!) gave to me. And that was really helpful.

Consider a situation where you give two levels of test (T) and two dose levels of reference (R), and measure the effect of all four treatments.
This gives you four data points:
Effect of T at dose level 1
Effect of T at dose level 2
Effect of R at dose level 1
Effect of R at dose level 2

Now imagine a line drawn through the points for T and also a line drawn through the points for R.
Importantly, to assure that there is dose-response-relationship (in other words: to ensure sensitivity) both lines must have a slope that is significantly different from Zero. In addition, it is necessary to test that two slopes are not significantly different (departure from parallelism). This test should not be significant. If there is departure from parallelism then the two products are not similar.

Now for the really interesting stuff: Finney's approach is to compare on the dose-axis, not on the effect axis. This contrasts with many people's idea of comparability, but it makes good sense. It is simply "relative potency" and it avoids the problem of defining an equivalence margin in terms of effect. When there is no departure from parallelism then the horizontal difference between the two lines projected onto the logarithmic dose axis is constant. From this we can calculate the T:R ratio, and furthermore with some statistical black magic( ) also a confidence interval for the T:R ratio through the ANOVA's root mean square error.

And that's in fact that.
It is actually almost the same principles that are laid out in the Ph Eur test for biological substances (reference below). In don't think they use the term Finney Bioassay there but the principle is exactly the same.


Have Fun
Earlybird


References:
Ph Eur: 5.3. Statistical analysis of results of biological assays and tests

Formula for crossover-design could be found:
Guidance to establish equivalence or relative potency of safety and efficacy of a second entry short-acting beta-2 agonist metered dose inhaler

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Edit: Full quote removed. Please see this post! [Jaime]