## Sample size for 4-period 4-sequence crossover BE study [Power / Sample Size]

Hi,

I am in the process of conducting a sample size calculation for a crossover BE study. There are four-treatments (2xreference dosages & 2xtreatment dosages) & I plan to use the Williams' design as follows:

ABCD

BDAC

CADB

DCBA

The coefficient of variation from previous studies is 20% & I am assuming the true test reference ratio to be between 0.95 and 1.05. I want to demonstrate bioequivalence (0.80-1.25) at 90% power at the 5% level.

Using these figures, if it was a standard AB/BA crossover, I estimate that I would require 12 individuals to complete each arm - is this correct? I am unsure how this calculation is extended to fit the 4x4 design - do I simply randomise 12 more individuals to each of the remaining two sequences?

Further, if I planned to have just 1 treatment dose changing the design as follows:

ABC

BCA

CAB

Is it reasonable to randomise 12 individuals per sequence?

I really appreciate any help on this question.

Best wishes,

Bryony

Edit: Category changed; see also this post #1. [Helmut]

I am in the process of conducting a sample size calculation for a crossover BE study. There are four-treatments (2xreference dosages & 2xtreatment dosages) & I plan to use the Williams' design as follows:

ABCD

BDAC

CADB

DCBA

The coefficient of variation from previous studies is 20% & I am assuming the true test reference ratio to be between 0.95 and 1.05. I want to demonstrate bioequivalence (0.80-1.25) at 90% power at the 5% level.

Using these figures, if it was a standard AB/BA crossover, I estimate that I would require 12 individuals to complete each arm - is this correct? I am unsure how this calculation is extended to fit the 4x4 design - do I simply randomise 12 more individuals to each of the remaining two sequences?

Further, if I planned to have just 1 treatment dose changing the design as follows:

ABC

BCA

CAB

Is it reasonable to randomise 12 individuals per sequence?

I really appreciate any help on this question.

Best wishes,

Bryony

Edit: Category changed; see also this post #1. [Helmut]

### Complete thread:

- Sample size for 4-period 4-sequence crossover BE studyBryony Simmons 2018-02-01 12:16 [Power / Sample Size]
- function sampleN.TOST of package PowerTOST Helmut 2018-02-01 13:01
- Alpha adjustment in higher order crossover d_labes 2018-02-01 14:01
- Deficiencies Helmut 2018-02-01 15:48
- Deficiencies nobody 2018-02-01 17:10
- Deficiencies d_labes 2018-02-01 18:57
- Deficiencies Relaxation 2018-02-02 11:12
- Deficiencies nobody 2018-02-02 12:49
- Deficiencies Helmut 2018-02-02 16:14
- Deficiencies Relaxation 2018-02-02 19:41
- alpha... where is omega? Astea 2018-02-02 21:45
- α and no ω Helmut 2018-02-02 23:39
- TIE for NTIDs d_labes 2018-02-04 12:40
- TIE for NTIDs Astea 2018-02-04 20:04
- TIE for NTIDs Helmut 2018-02-05 01:01
- TIE for NTIDs d_labes 2018-02-05 16:40
- TIE for NTIDs Helmut 2018-02-05 17:49
- TIE for NTIDs d_labes 2018-02-05 22:17
- TIE for NTIDs Helmut 2018-02-06 12:34

- TIE for NTIDs d_labes 2018-02-05 22:17

- TIE for NTIDs Helmut 2018-02-05 17:49

- TIE for NTIDs d_labes 2018-02-05 16:40
- TIE for NTIDs d_labes 2018-02-05 16:35
- bow TIE for NTIDs Astea 2018-02-05 17:52
- bow TIE for NTIDs Helmut 2018-02-05 18:10
- 111.11 for NTIDs Astea 2018-02-05 19:27
- 111.11 for NTIDs Helmut 2018-02-06 00:12

- 111.11 for NTIDs Astea 2018-02-05 19:27
- bow TIE for NTIDs d_labes 2018-02-05 22:33

- bow TIE for NTIDs Helmut 2018-02-05 18:10

- bow TIE for NTIDs Astea 2018-02-05 17:52

- TIE for NTIDs Helmut 2018-02-05 01:01

- TIE for NTIDs Astea 2018-02-04 20:04

- TIE for NTIDs d_labes 2018-02-04 12:40

- α and no ω Helmut 2018-02-02 23:39

- alpha... where is omega? Astea 2018-02-02 21:45

- Deficiencies Relaxation 2018-02-02 19:41

- Deficiencies Relaxation 2018-02-02 11:12

- Deficiencies Helmut 2018-02-01 15:48

- Alpha adjustment in higher order crossover d_labes 2018-02-01 14:01

- function sampleN.TOST of package PowerTOST Helmut 2018-02-01 13:01