title: Change-point models to estimate the limit of detection.
abstract: In many biological and environmental studies, measured data is subject to a limit of detection. The limit of detection is generally defined as the lowest concentration of analyte that can be differentiated from a blank sample with some certainty. Data falling below the limit of detection is left censored, falling below a level that is easily quantified by a measuring device. A great deal of interest lies in estimating the limit of detection for a particular measurement device. In this paper, we propose a change-point model to estimate the limit of detection by using data from an experiment with known analyte concentrations. Estimation of the limit of detection proceeds by a two-stage maximum likelihood method. Extensions are considered that allow for censored measurements and data from multiple experiments. A simulation study is conducted demonstrating that in some settings the change-point model provides less biased estimates of the limit of detection than conventional methods. The proposed method is then applied to data from an HIV pilot study.
authors.affiliation: The EMMES Corporation, Rockville, Maryland 20850, U.S.A.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: May
authors.forename: Haitao
authors.initials: H
authors.lastname: Chu
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Ibrahim
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hudgens
authors.forename: Abigail C
authors.initials: AC
authors.lastname: Lees
authors.forename: David M
authors.initials: DM
authors.lastname: Margolis
mesh_terms: D003198:Computer Simulation; D006678:HIV / Q000235:genetics; D015658:HIV Infections / Q000097:blood; D006801:Humans; D016013:Likelihood Functions; D057230:Limit of Detection; D015233:Models, Statistical; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D012367:RNA, Viral
keywords: change point; limit of detection; linear calibration curve; two-stage maximum likelihood