Review of potentials and limitations of indirect approaches for estimating reference limits/intervals of quantitative procedures in laboratory medicine

Abstract

Reference intervals (RIs) can be determined by direct and indirect procedures. Both approaches identify a reference population from which the RIs are defined. The crucial difference between direct and indirect methods is that direct methods select particular individuals after individual anamnesis and medical examination have confirmed the absence of pathological conditions. These individuals form a reference subpopulation. Indirect methods select a reference subpopulation in which the individuals are not identified. They isolate a reference population from a mixed population of patients with pathological and non-pathological conditions by statistical reasoning. At present, the direct procedure internationally recommended is the “gold standard”. It has, however, the disadvantage of high expenses which cannot easily be afforded by most medical laboratories. Therefore, laboratories adopt RIs established by direct methods from external sources requiring a high responsibility for transference problems which are usually neglected by most laboratories. These difficulties can be overcome by indirect procedures which can easily be performed by most laboratories without causing economic problems. The present review focuses on indirect approaches. Various procedures are presented with their benefits and limitations. Preliminary simulation studies indicate that more recently developed concepts are superior to older approaches.

Two new methods for severity assessment of wheat stripe rust caused by Puccinia striiformis f. sp. tritici

“…In the field of medicine, the reference ranges of the normal values of various medical indicators are the normal fluctuation ranges of the corresponding indicators of the vast majority of normal people, and they are used to evaluate whether the measured corresponding indicators are normal and can provide a basis for disease diagnosis, health assessment, and disease treatment ( Horn and Pesce, 2003 ; Sun and Xu, 2014 ; Haeckel et al., 2021 ; Yang et al., 2022 ). There are many methods to determine the medical reference ranges ( Horn and Pesce, 2003 ; Sun and Xu, 2014 ; Haeckel et al., 2021 ; Yang et al., 2022 ). A medical reference range is usually determined by using normal distribution method or percentile method, mainly depending on whether the related data conform to a normal distribution ( Horn and Pesce, 2003 ; Sun and Xu, 2014 ; Haeckel et al., 2021 ).…”

“…There are many methods to determine the medical reference ranges ( Horn and Pesce, 2003 ; Sun and Xu, 2014 ; Haeckel et al., 2021 ; Yang et al., 2022 ). A medical reference range is usually determined by using normal distribution method or percentile method, mainly depending on whether the related data conform to a normal distribution ( Horn and Pesce, 2003 ; Sun and Xu, 2014 ; Haeckel et al., 2021 ). When the related data of the corresponding indicator conform to a normal distribution or can be transformed into a normal distribution via data transformation, normal distribution method can be used to estimate the reference range, otherwise, when the data do not conform to a normal distribution, percentile method can be used ( Horn and Pesce, 2003 ; Sun and Xu, 2014 ; Haeckel et al., 2021 ).…”

“…A medical reference range is usually determined by using normal distribution method or percentile method, mainly depending on whether the related data conform to a normal distribution ( Horn and Pesce, 2003 ; Sun and Xu, 2014 ; Haeckel et al., 2021 ). When the related data of the corresponding indicator conform to a normal distribution or can be transformed into a normal distribution via data transformation, normal distribution method can be used to estimate the reference range, otherwise, when the data do not conform to a normal distribution, percentile method can be used ( Horn and Pesce, 2003 ; Sun and Xu, 2014 ; Haeckel et al., 2021 ). In this study, the reference ranges at different levels (90%, 95%, and 99%) of the actual percentages of lesion areas corresponding to each severity class of wheat stripe rust were estimated by referring to the method for determining medical reference ranges, and the determined 90%, 95%, and 99% reference ranges of the actual percentages of lesion areas corresponding to each severity class can be considered as the fluctuation ranges of the actual percentages of lesion areas of 90%, 95%, and 99% of diseased leaves of the corresponding severity class, respectively.…”

“…When the method proposed in this study is used to determine the reference ranges at different levels of the actual percentages of lesion areas corresponding to each severity class of a plant disease, the determination method of the reference ranges should be modified or changed if the actual percentage data do not conform to a normal distribution. The actual percentage data can be transformed into a normal distribution through data transformation and then the normal distribution method can be used to determine the reference ranges, or the other methods including the percentile method can be used ( Horn and Pesce, 2003 ; Sun and Xu, 2014 ; Haeckel et al., 2021 ).…”

Comparison of age- and sex-dependent reference limits derived from distinct sources for metabolic measurands in basic liver diagnostics

“…Meanwhile, the estimation of reference limits has evolved in a new direction through big data approaches [2]. While established direct methods rely on highly selected reference individuals, big data approaches utilize so-called real-world data to indirectly estimate reference limits within the given population [3]. Because these data typically contain mixed populations that may include both diseased and healthy individuals, mixture deconvolution approaches are required, as well as careful interpretation of the output.…”