Change-point models to estimate the limit of detection

• Published in: Statistics in medicine Vol. 32; no. 28; pp. 4995 - 5007
• Main Authors: May, Ryan C., Chu, Haitao, Ibrahim, Joseph G., Hudgens, Michael G., Lees, Abigail C., Margolis, David M.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 10.12.2013; Wiley Subscription Services, Inc
• Subjects: change point; Computer Simulation; Estimating techniques; HIV; HIV - genetics; HIV Infections - blood; Human immunodeficiency virus; Humans; Likelihood Functions; Limit of Detection; linear calibration curve; Maximum likelihood method; Measurement; Models, Statistical; Real-Time Polymerase Chain Reaction; RNA, Viral - chemistry; RNA, Viral - genetics; Simulation; two-stage maximum likelihood; linear calibration curve; limit of detection; two-stage maximum likelihood; change point
• ISSN: 0277-6715; 1097-0258; 1097-0258
• DOI: 10.1002/sim.5872

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. Copyright © 2013 John Wiley & Sons, Ltd.