## Higher-order crossovers [Power / Sample Size]

Hello,

I would like to obtain an advice on BE study sample size estimation.

Let’s say, we are planning a 2x2 crossover study for BE, and the intra-subject coefficient of variation for our test compound, from a prior study, is 23%. The assumed geometric mean ratio is 1.00, alpha is 0.05, equivalence limits are 80%-125%, and we desire power of 80%. These criteria result in an overall sample size of 20 subjects, or 10 per sequence.

Subsequently, we want to add 2 extra dose levels of our test drug, resulting in a 4x4 crossover trial. Let’s assume that %CV and GMR are not changing, as no further data is available. For this new scenario, is it appropriate to: 1) use the original sample size of N=20 and simply divide it over 4 sequences (5 per sequence), or 2) take the original per sequence sample size of 10 and multiply by 4 to get 40 subjects overall needed? In either case 1) or 2), is there a supporting reference you can provide?

Thanks,

Sveta

Edit: Category and subject line changed; see also this post #1 and #2. [Helmut]

I would like to obtain an advice on BE study sample size estimation.

Let’s say, we are planning a 2x2 crossover study for BE, and the intra-subject coefficient of variation for our test compound, from a prior study, is 23%. The assumed geometric mean ratio is 1.00, alpha is 0.05, equivalence limits are 80%-125%, and we desire power of 80%. These criteria result in an overall sample size of 20 subjects, or 10 per sequence.

Subsequently, we want to add 2 extra dose levels of our test drug, resulting in a 4x4 crossover trial. Let’s assume that %CV and GMR are not changing, as no further data is available. For this new scenario, is it appropriate to: 1) use the original sample size of N=20 and simply divide it over 4 sequences (5 per sequence), or 2) take the original per sequence sample size of 10 and multiply by 4 to get 40 subjects overall needed? In either case 1) or 2), is there a supporting reference you can provide?

Thanks,

Sveta

Edit: Category and subject line changed; see also this post #1 and #2. [Helmut]

### Complete thread:

- Higher-order crossoverssweiner 2020-01-22 20:22 [Power / Sample Size]
- Purpose of the study? Helmut 2020-01-23 13:48
- Higher-order crossovers sweiner 2020-01-26 16:50