Determination of Bioassay Cut Point Using Confidence Limit of Percentile

• Activity Number: 487
• Type: Contributed
• Date/Time: Wednesday, August 7, 2013 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Meiyu Shen*+ and Xiaoyu Dong and Youngsook Jeon and Yi Tsong
• Companies: FDA and FDA and FDA and FDA
• Keywords: Bioassay ; cut point estimation ; statistical interval ; percentile

Abstract

Cut point of the assay is the level of response of the assay at or above which a sample is defined to be positive and below which it is defined to be negative. Food and Drug Administration Guidance for Industry Assay Development for Immunogenicity Testing of Therapeutic recommends that the cut point have an upper negative limit of approximately 95 percent. The sample percentile is a point estimate with variability decreasing with the larger sample size. We conducted an extensive literature review on the estimation of the confidence limits for percentiles and performed comparison of the selected methods for bias and the coverage percentage of the extreme values. We evaluate sample percentile, the confidence interval of normal percentile (Charkraborti and Li, 2007), confidence interval of Gamma percentile (Wilson and Hilferty, 1931), and a nonparametric interval. It is shown that the coverage percentage of sample percentile is much larger than (1 - percentage) with the number of assays conducted in practice. We recommend using the lower confidence limit of the percentile for cut point determination and one of the confidence limits of three evaluated percentiles.