Reference Interval Estimation from Mixed Distributions using Truncation Points and the Kolmogorov-Smirnov Distance (kosmic)

Zierk J, Arzideh F, Kapsner L, Prokosch HU, Metzler M, Rauh M (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 10

Article Number: 1704

Journal Issue: 1

DOI: 10.1038/s41598-020-58749-2

Abstract

Appropriate reference intervals are essential when using laboratory test results to guide medical decisions. Conventional approaches for the establishment of reference intervals rely on large samples from healthy and homogenous reference populations. However, this approach is associated with substantial financial and logistic challenges, subject to ethical restrictions in children, and limited in older individuals due to the high prevalence of chronic morbidities and medication. We implemented an indirect method for reference interval estimation, which uses mixed physiological and abnormal test results from clinical information systems, to overcome these restrictions. The algorithm minimizes the difference between an estimated parametrical distribution and a truncated part of the observed distribution, specifically, the Kolmogorov-Smirnov-distance between a hypothetical Gaussian distribution and the observed distribution of test results after Box-Cox-transformation. Simulations of common laboratory tests with increasing proportions of abnormal test results show reliable reference interval estimations even in challenging simulation scenarios, when <20% test results are abnormal. Additionally, reference intervals generated using samples from a university hospital’s laboratory information system, with a gradually increasing proportion of abnormal test results remained stable, even if samples from units with a substantial prevalence of pathologies were included. A high-performance open-source C++ implementation is available at https://gitlab.miracum.org/kosmic.

Authors with CRIS profile

Jakob Zierk Department of Paediatrics and Adolescent Medicine Lorenz Kapsner Department of Psychiatry and Psychotherapy Hans-Ulrich Prokosch Lehrstuhl für Medizinische Informatik Markus Metzler Professur für Kinder- und Jugendmedizin mit dem Schwerpunkt Pädiatrische Onkologie und Hämatologie Manfred Rauh Department of Paediatrics and Adolescent Medicine

Involved external institutions

Universität zu Köln DE Germany (DE)

How to cite

APA:

Zierk, J., Arzideh, F., Kapsner, L., Prokosch, H.-U., Metzler, M., & Rauh, M. (2020). Reference Interval Estimation from Mixed Distributions using Truncation Points and the Kolmogorov-Smirnov Distance (kosmic). Scientific Reports, 10(1). https://doi.org/10.1038/s41598-020-58749-2

MLA:

Zierk, Jakob, et al. "Reference Interval Estimation from Mixed Distributions using Truncation Points and the Kolmogorov-Smirnov Distance (kosmic)." Scientific Reports 10.1 (2020).

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