Bioequivalence and Bioavailability Forum

Dear BL,

For four way crossover design with following sequences
    Tfasted  Rfasted  Tfed  Rfed
    Rfasted  Tfasted  Rfed  Tfed
We don't need to built many ANOVA. What you can do is add diet(fed or fast) as factor in your ANOVA and accordingly modify other factors.
Then using repeated statement in PROC mixed calculate residual variability for two diets from which intra subject variabilty under fed and fasted state can be calculated separately.

And for comparisons like Tfasted vs Rfasted, Tfed vs Rfed , use estimate statement which will provide estimated difference with confidence intervals. And for other comparisons like Tfasted vs Tfed etc. we can calculate ratios from LSMeans obtained through model.

But problem with this design, as HS said, is

❝ The variability in fed state may be different to fasted state. Since you have to power the study for the 'weakest' arm, the 4-way study may need more treatments than two 2×2 studies.

But design is good replacement for two or more studies if there is not much difference in variabilty of drug under fed and fasted state.

Regards,
GSTATS
http://www.gstatsolutions.com/Medical%20Research.html