A pipeline for the fully automated estimation of continuous reference intervals using real-world data

Ammer T, Schützenmeister A, Prokosch HU, Rauh M, Rank CM, Zierk J (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Book Volume: 13

Article Number: 13440

Journal Issue: 1

DOI: 10.1038/s41598-023-40561-3

Abstract

Reference intervals are essential for interpreting laboratory test results. Continuous reference intervals precisely capture physiological age-specific dynamics that occur throughout life, and thus have the potential to improve clinical decision-making. However, established approaches for estimating continuous reference intervals require samples from healthy individuals, and are therefore substantially restricted. Indirect methods operating on routine measurements enable the estimation of one-dimensional reference intervals, however, no automated approach exists that integrates the dependency on a continuous covariate like age. We propose an integrated pipeline for the fully automated estimation of continuous reference intervals expressed as a generalized additive model for location, scale and shape based on discrete model estimates using an indirect method (refineR). The results are free of subjective user-input, enable conversion of test results into z-scores and can be integrated into laboratory information systems. Comparison of our results to established and validated reference intervals from the CALIPER and PEDREF studies and manufacturers’ package inserts shows good agreement of reference limits, indicating that the proposed pipeline generates high-quality results. In conclusion, the developed pipeline enables the generation of high-precision percentile charts and continuous reference intervals. It represents the first parameter-less and fully automated solution for the indirect estimation of continuous reference intervals.

Authors with CRIS profile

Involved external institutions

Roche Diagnostics GmbH Germany (DE)

How to cite

APA:

Ammer, T., Schützenmeister, A., Prokosch, H.-U., Rauh, M., Rank, C.M., & Zierk, J. (2023). A pipeline for the fully automated estimation of continuous reference intervals using real-world data. Scientific Reports, 13(1). https://doi.org/10.1038/s41598-023-40561-3

MLA:

Ammer, Tatjana, et al. "A pipeline for the fully automated estimation of continuous reference intervals using real-world data." Scientific Reports 13.1 (2023).

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