Bioequivalence and Bioavailability Forum

Hi ElMaestro!

❝ ❝ A term for the stage should be included in the ANOVA model. However, the guideline does not clarify what the consequence should be if it is statistically significant. In principle, the data sets of both stages could not be combined.

❝

❝ We cannot combine data for stage 1 an stage 2 in our analyses, or what is meant there?

Similar to the never-ending story of including a term if a conventional study was performed in more than one group.

Potvin et al. used a stage-term in the second stage, but

[…] pooling data from stages 1 and 2 were always allowed, even if there was a statistically significant difference between the results from the two stages.

because

[The method] does not require poolability criteria (or at least should know whether results from both stages are poolable before sample analysis, i.e. base poolability on study conduct such as subject demographics, temporal considerations, use of same protocol, use of same site, etc., rather than a statistical test of poolability).

A term for stage makes sense. Potvin’s Example 2 (94.12% CI):

87.94–117.05% (with stage term, 17 df)
88.16–116.72% (without stage term, 18 df)

The stage term (lower df) widens the CI (conservative). Since the stage term is between subjects its power is low. Nevertheless, even if there is no ‘true’ effect we expect to get a false positive at the level of the test.