Bioequivalence and Bioavailability Forum

Dear Discu-Tanten!

Helmut: Two posts - excellent and comprehensive as always. Nearly nothing left to add.

But to me throw in my own two cents into the gladiator's arena:

I had the same preferences:

❝ 1. Full model: Code everything as it happened in the study. Yes, three treatments in three periods, six sequences. Full stop.

❝ 2. EMA’s: Bad style. Jury out, verdict pending.

❝ 3. Recoding: The wonderful thing with the cross-over is that we can forget period-effects; what if P1≠P2≠P3 and some responses are shifted from one period to another? Pray for balance!

To 1.: Intuitively this approach is for me the preferred, as said "Code everything as it happened". But of course it has pre-conditions. Not at least the variance homogeneity.

To 3.: IMHO especially the argument of period effects not considered adequate if recoding of the periods is done speaks against it.

To 2.: Regarding the evaluation pairwise (not considering the rest of the data) I'm meanwhile not totally convinced that this is bad style.

Having in mind Stephen Senn's basic estimator approach¹⁾:
Calculate the difference (of log-transformed metrics) you are interested in via intra-subject contrasts and analyse them as sequence group stratified mean (intercept of an ANOVA with sequence as effect) goes along the same line. Senn calls this approach "simple and fairly robust", don't know exactly whatever robust here means.

And having in mind some simulation results coming soon .

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¹⁾ Stephen Senn
Cross-over Trials in Clinical Research
Second edition, Chapter 5.4.1
John Wiley, Chichester 2002