Sample Size and Power Analysis for Endometrial Safety Studies

ABSTRACT

Endometrial safety studies are required for the approval of progestin components. The Committee for Proprietary Medicinal Products requirement is the actual percentage below 2% and the upper limit of the one-sided exact 95% confidence interval not more than 2% above the point estimate. The more recent U.S. Food and Drug Administration requirement is the actual percentage  ≤ 1% and the upper limit of the one-sided exact 95% confidence interval ≤4%. I studied the sample size and power needed to satisfy both requirements based on the exact confidence intervals for the binomial parameter and the Poisson parameter. I discovered that a larger sample size does not always lead to a higher power. I presented a best sample size that satisfies both requirements and recommended that the patient enrollment should be closely monitored during the study.

Key Words:

• Endometrial safety study
• Incidence rate
• Risk rate.

ACKNOWLEDGMENTS

I want to thank the two anonymous referees for their useful suggestions. I am also grateful to my colleague Erhard Quebe-Fehling for allowing me the opportunity to work on the sample size for endometrial safety studies.

Notes

^aThere is a jump in power compared with the previous sample size.

^aThere is a jump in power compared with the previous total exposure years.