title: Repeated significance tests of linear combinations of sensitivity and specificity of a diagnostic biomarker.
abstract: A sequential design is proposed to test whether the accuracy of a binary diagnostic biomarker meets the minimal level of acceptance. The accuracy of a binary diagnostic biomarker is a linear combination of the marker's sensitivity and specificity. The objective of the sequential method is to minimize the maximum expected sample size under the null hypothesis that the marker's accuracy is below the minimal level of acceptance. The exact results of two-stage designs based on Youden's index and efficiency indicate that the maximum expected sample sizes are smaller than the sample sizes of the fixed designs. Exact methods are also developed for estimation, confidence interval and p-value concerning the proposed accuracy index upon termination of the sequential testing. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
authors.affiliation: College of Applied Sciences, Beijing University of Technology, Beijing, 100124, China.
authors.forename: Mixia
authors.initials: M
authors.lastname: Wu
authors.affiliation: Abbott Labs Vascular Division, 3200 Lakeside Dr., Santa Clara, 95054, CA, U.S.A.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of Statistics, George Washington University, 801 22nd Street NW, Washington, DC 20052, U.S.A.
authors.forename: Zhaohai
authors.initials: Z
authors.lastname: Li
authors.affiliation: Biostatistics and Bioinformatics Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6100 Executive Blvd., MD 20852, Rockville, U.S.A.
authors.forename: Aiyi
authors.initials: A
authors.lastname: Liu
mesh_terms: D015415:Biomarkers; D006801:Humans; D012107:Research Design; D018401:Sample Size; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers
keywords: Youden's index; expected sample size; inference upon early stopping; sensitivity; sequential testing; specificity; two-stage designs; type I error