Bioequivalence and Bioavailability Forum

Dear d_labes,

now assume beman goes ahead with this study and he collects a bunch of data.
Subjects are dosed once with each treatment, so the logic that applies in 2,2,2-BE studies applies here as well, implying that we ignore the little issue of potentially correlated residuals due to intra-subject phenomena (subject as fixed, linear model).

Bottomline, from each subject we will have five (we hope) measurements, a period coding, a sequence coding, and a dose level coding. PROC GLM does the trick and yes we can throw sequence and period into the pot if we wish. We get LSMeans for all five treatment levels or just plain means. No big deal, but it should of course be specified in the protocol which one to use. And if someone makes a big fuss about using LSMeans or worries about imbalance then we just throw a little quote from the SAS manual back at them:
"(...)LS-means are, in effect, within-group means appropriately adjusted for the other effects in the model. More precisely, they estimate the marginal means for a balanced population(...)."

We can even beef the entire thing up with PROC MIXED to allow for intra-subject correlations and issues surrounding dropouts, I guess. In that case we will not have LSMeans but maximum likelihood effects extractable from the model's b-vector.

But having said that, I would also like to say that Dr_Dan's idea of just using three levels (lowest, middle, highest) also appeals a lot to me.