Bioequivalence and Bioavailability Forum

Dear Helmut, dear all,

❝ In such a design treatments in periods 1 and 2 can be compared in fasted state and in periods 3 and 4 in fed state as a conventional cross-over.

❝ Additionally Tfed vs. Tfasted and Rfed vs. Rfasted can be evaluated as a paired design (with high power, but avoiding confounding issues).

Just as a matter of curiosity (and I know there are other difficulties with 4-period trials, such as a higher risk of drop-out). To avoid the problem of assumptions regarding period effects, discussed by D.Labes and Helmut, what would you think of a 4-period trial with the following sequences:

• T_fasted  R_fasted  T_fed   R_fed
  
• R_fasted  T_fasted  R_fed   T_fed
  
• T_fed     R_fed     T_fasted R_fasted
  
• Rfed     Tfed     Rfasted Tfasted


The idea would then be to analyse the data as suggested by Helmut (as two usual 2x2 trials, one for fasted, one for fed) as if there were two groups of subjects in the trial (just like in a large trial when the subjects have to be split due to limited capacities of the facilities), and then to do the "paired design (with high power, but avoiding confounding issues)", without the problem of the sequence effect.

Practically there would certainly be precautions to be taken, such as housing separately the fed and fasting subjects, to avoid confusions (and I wouldn't like to be fasting, and to smell the eggs and bacon of the other guys ), but would it make any sense on a statistical point of view, or is my idea complete nonsense ?

Regards
Ohlbe