Related Experiment Video
Updated: Aug 15, 2025
07:35
Selecting Multiple Biomarker Subsets with Similarly Effective Binary Classification Performances
Published on: October 11, 2018
7.6K
An Approach for Evaluating Potential Screening Thresholds Using Biomarker Population Distribution and Analytical
Matthew P A Henderson1,2, Pranesh Chakraborty1,2
1Newborn Screening Ontario, Children's Hospital of Eastern Ontario, Ottawa, Canada.
The Journal of Applied Laboratory Medicine
|January 7, 2023
Summary
Setting screening thresholds for galactose-1-phosphate uridylyltransferase (GALT) activity testing balances false negatives and follow-up tests. A conservative threshold minimizes false negatives but increases repeat testing needs.
Area of Science:
- Laboratory medicine
- Newborn screening
Background:
- Screening tests in laboratory medicine identify samples needing further analysis.
- Threshold selection is influenced by population biomarker distribution and assay imprecision.
Purpose of the Study:
- To estimate the impact of analytical imprecision on newborn screening for galactose-1-phosphate uridylyltransferase (GALT) activity.
- To evaluate the trade-offs in selecting screening thresholds.
Main Methods:
- A simulation model was developed using population GALT activity distribution and assay imprecision data.
- The simulation estimated samples requiring repeat analysis and potential false negatives.
Main Results:
- A conservative screening threshold (6 standard deviations from confirmation) virtually eliminated false negatives due to imprecision.
- This approach increased follow-up testing by 0.15% annually (222 samples).
Conclusions:
- Threshold selection in screening algorithms must consider repeat testing and false-negative rates.
- Optimizing screening requires balancing sensitivity and specificity based on analytical imprecision.
