Next Article in Journal
Newborn Screening for Selected Disorders in Nepal: A Pilot Study
Next Article in Special Issue
Including Classical Galactosaemia in the Expanded Newborn Screening Panel Using Tandem Mass Spectrometry for Galactose-1-Phosphate
Previous Article in Journal
Thalassemias: An Overview
Previous Article in Special Issue
Reliability of Neonatal Screening Results
Open AccessArticle

The Importance of Assay Imprecision near the Screen Cutoff for Newborn Screening of Lysosomal Storage Diseases

Department of Chemistry, University of Washington, Seattle, WA 98195, USA
*
Authors to whom correspondence should be addressed.
Int. J. Neonatal Screen. 2019, 5(2), 17; https://doi.org/10.3390/ijns5020017
Received: 18 December 2018 / Revised: 20 March 2019 / Accepted: 22 March 2019 / Published: 27 March 2019
(This article belongs to the Special Issue Selected Papers from 11th ISNS European Regional Meeting)
For newborn screening (NBS) of lysosomal storage diseases, programs measure enzymatic activities in dried blood spots (DBS) and, in most cases, act on samples where the measurement is below a specific cutoff value. The rate of false positives and negatives in any NBS program is of critical importance. The measured values across a population of newborns are governed by many factors, and in this article we focus on assay imprecision. Assay parameters including the Analytical Range and the Z-Factor have been discussed as a way to compare assay performance for NBS of lysosomal storage diseases. Here we show that these parameters are not rigorously connected to the rate of false positives and negatives. Rather, it is the assay imprecision near the screen cutoff that is the most important parameter that determines the rate of false positives and negatives. We develop the theoretical treatment of assay imprecision and how it is linked to screen performance. What emerges is a useful type of parametric plot that allows for rigorous assessment of the effect of assay imprecision on the rate of false positives and false negatives that is independent of the choice of screen cutoff value. Such plots are useful in choosing cutoff values. They also show that a high assay imprecision cannot be overcome by changing the cutoff value or by use of postanalysis, statistical tools. Given the importance of assay imprecision near the cutoff, we propose that quality control DBS are most useful if they span a range of analyte values near the cutoff. Our treatment is also appropriate for comparing the performance of multiple assay platforms that each measure the same quantity (i.e., the enzymatic activity in DBS). The analysis shows that it is always best to use the assay platform that gives the lowest imprecision near the cutoff. View Full-Text
Keywords: newborn screening; cutoff values; assay imprecision; false positives; false negatives; screening assays newborn screening; cutoff values; assay imprecision; false positives; false negatives; screening assays
Show Figures

Figure 1

MDPI and ACS Style

Robinson, B.H.; Gelb, M.H. The Importance of Assay Imprecision near the Screen Cutoff for Newborn Screening of Lysosomal Storage Diseases. Int. J. Neonatal Screen. 2019, 5, 17.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop