Sample Size Calculation for Phase 3 Non-Inferiority Trial of Nebivolol vs Bisoprolol for Hypertension in China

To calculate the sample size for the phase 3 clinical trial, the following steps can be taken:

1. Determine the non-inferiority margin: This is the maximum difference between the mean sitting DBP change for Nebivolol and Bisoprolol that would still be considered acceptable. Let's assume a non-inferiority margin of 3 mmHg.

2. Determine the expected mean sitting DBP change for each treatment: This can be based on the results of previous studies or expert opinion. Let's assume the expected mean sitting DBP change for Nebivolol is 8 mmHg and for Bisoprolol is 9 mmHg.

3. Determine the standard deviation (SD) of the mean sitting DBP change for each treatment: This can also be based on previous studies or expert opinion. Let's assume the SD for Nebivolol is 5 mmHg and for Bisoprolol is 6 mmHg.

4. Calculate the sample size using the following formula:

n = [(Zα/2 + Zβ) * (SD/∆)]^2

where: n = sample size per treatment group Zα/2 = the Z-value for the chosen type one error (0.025) from a standard normal distribution (1.96) Zβ = the Z-value for the chosen power (0.90) from a standard normal distribution (1.28) SD = the pooled standard deviation of the mean sitting DBP change for both treatments ((SD_Nebivolol^2 + SD_Bisoprolol^2)/2)^0.5 ∆ = the non-inferiority margin (3 mmHg)

Using the above values, the sample size per treatment group would be:

n = [(1.96 + 1.28) * (5.5/3)]^2 = 60.4

Rounding up to the nearest whole number, the final sample size per treatment group would be 61.

Therefore, the total sample size for the study would be 122 (61 per treatment group).