Bioequivalence and Bioavailability Forum

Hi Olivbood,

❝ Since the number of treatments is relatively high, the number of blood samples drawn from each subject would be quite high and the study would be time consuming (thus subjects would be more likely to dropout).

Yes and no. The loss in power due to dropouts is overrated by many. Try the function pa.ABE() in PowerTOST. Unless the drug is nasty (i.e., drug-related AEs leading to withdrawals) it should not hurt. Concerning the blood volume: I just performed a five (!) period Xover with 19 samples/period. Total blood volume (including pre- / post-study clin. chemistry) was 440 mL. In short: Develop a better bioanalytical method.

❝ In such a case, a balanced incomplete block design with 2 periods and 6 sequences( where each subject would take only 2 treatments) is appealing.

❝ However, I guess going with such a design have its own disadvantages such as an increase in sample size and unbalance between the sequences would be more problematic.

Maybe. Though BIBDs are mentioned in most textbooks of BE, I didn’t see a single one in my entire career. Phase III is another story, of course.

❝ Do you know if such a design is practicable and likely to be accepted by the regulatory agencies?

(1) Duno and (2) why not? However, expect questions since assessors likely are not familiar with their application in BE.

❝ Also, how should I proceed to power such a study, if possible using the package powerTOST? Would I be bound to perform simulations and base my sample size on expected power?

Good question, next question.