LKC Technologies, Gaithersburg, MD, USA.
Department of Clinical Physics and Bioengineering, Royal Hospital for Children, NHS Greater Glasgow and Clyde, Glasgow, UK.
Doc Ophthalmol. 2021 Oct;143(2):155-170. doi: 10.1007/s10633-021-09831-1. Epub 2021 Apr 21.
Establishing robust reference intervals for clinical procedures has received much attention from international clinical laboratories, with approved guidelines. Physiological measurement laboratories have given this topic less attention; however, most of the principles are transferable.
Herein, we summarise those principles and expand them to cover bilateral measurements and one-tailed reference intervals, which are common issues for those interpreting clinical visual electrophysiology tests such as electroretinograms (ERGs), visual evoked potentials (VEPs) and electrooculograms (EOGs).
The gold standard process of establishing and defining reference intervals, which are adequately reliable, entails collecting data from a minimum of 120 suitable reference individuals for each partition (e.g. sex, age) and defining limits with nonparametric methods. Parametric techniques may be used under some conditions. A brief outline of methods for defining reference limits from patient data (indirect sampling) is given. Reference intervals established elsewhere, or with older protocols, can be transferred or verified with as few as 40 and 20 suitable reference individuals, respectively. Consideration is given to small numbers of reference subjects, interpretation of serial measurements using subject-based reference values, multidimensional reference regions and age-dependent reference values. Bilateral measurements, despite their correlation, can be used to improve reference intervals although additional care is required in computing the confidence in the reference interval or the reference interval itself when bilateral measurements are only available from some of subjects.
Good quality reference limits minimise false-positive and false-negative results, thereby maximising the clinical utility and patient benefit. Quality indicators include using appropriately sized reference datasets with appropriate numerical handling for reporting; using subject-based reference limits where appropriate; and limiting tests for each patient to only those which are clinically indicated, independent and highly discriminating.
建立临床检验的稳健参考区间已经引起国际临床实验室的广泛关注，并制定了相关指南。生理测量实验室对此主题的关注较少；然而，大多数原则是可以转移的。
本文总结了这些原则，并将其扩展到双侧测量和单侧参考区间，这些都是解释临床视觉电生理学测试（如视网膜电图（ERG）、视觉诱发电位（VEP）和眼电图（EOG））的常见问题。
建立和定义可靠参考区间的金标准过程需要从每个分区（例如性别、年龄）的至少 120 名合适的参考个体中收集数据，并使用非参数方法定义界限。在某些条件下，可以使用参数技术。简要介绍了从患者数据（间接采样）定义参考限的方法。在其他地方建立的参考区间，或使用较旧的方案，可以分别使用少至 40 和 20 名合适的参考个体进行转移或验证。考虑到参考个体数量较少，使用基于个体的参考值对系列测量进行解释，多维参考区域和年龄相关的参考值。尽管双侧测量具有相关性，但可以使用它们来改善参考区间，尽管在双侧测量仅来自部分个体时，需要更加小心地计算参考区间的置信度或参考区间本身。
高质量的参考限值可最大限度地减少假阳性和假阴性结果，从而最大程度地提高临床实用性和患者受益。质量指标包括使用大小适当的参考数据集，并进行适当的数值处理以进行报告；在适当的情况下使用基于个体的参考限值；并将每个患者的测试限制在那些具有临床指征、独立和高度区分的测试上。
