29 – 29 - Statistical Issues Specific to Therapeutic Areas, Power and Sample Size Calculations, and Trial Monitoring
An Alternate Method to Find the Confidence Interval for the Difference Between Two Proportions of Rare Event
Ruji Yao
Merck & Co., Inc.
In a clinical trial, it is common to have an adverse event summary table to show the difference of event rates and their 95% confidence intervals (CI). The Miettinen, O. and Nurminen, M (M&N) [1] method is often used for this summary. When dealing with a difference of rare events, one possible concern is the normality assumption. In this presentation, we propose a new method for obtaining the CI, which is sometimes more suitable for computing the difference of two proportions of rare event. First, we will use the formula of Exact (Clopper-Pearson) [2] Confidence Limits to define the posterior distributions on observed data. This help us to avoid the need to pick up a Beta (a,b) prior in a Bayesian method. We then calculate the confidence interval directly from these posterior distributions without making a normality assumption for the critical values. Most importantly, our method only makes use of the binomial assumption on the observed data. Compared with the M&N method, we find that our method has very similar results when the differences of rates are in the normal range, but a much narrower widths for the CI when considering differences between rare events.