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.
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.