Introduction

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.

Methods

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).

Results

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.

Discussion

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.

中文翻译：

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临床视觉电生理学参考范围

 介绍

为临床程序建立可靠的参考区间已受到国际临床实验室的广泛关注，并已获得批准的指南。生理测量实验室对这个话题的关注较少。然而，大多数原则是可以转移的。

 方法

在此，我们总结了这些原则，并将其扩展到双边测量和单尾参考区间，这是解释临床视觉电生理学测试（例如视网膜电图（ERG）、视觉诱发电位（VEP）和眼电图（EOG）的常见问题。

 结果

建立和定义足够可靠的参考区间的黄金标准过程需要从每个分区（例如性别、年龄）的至少 120 个合适的参考个体收集数据，并使用非参数方法定义限制。在某些条件下可以使用参数化技术。给出了根据患者数据（间接采样）定义参考限值的方法的简要概述。在其他地方或使用旧协议建立的参考区间可以分别用少至 40 和 20 名合适的参考个体进行转移或验证。考虑到少量参考受试者、使用基于受试者的参考值、多维参考区域和年龄相关参考值对连续测量的解释。双边测量尽管具有相关性，但可用于改善参考区间，尽管当双边测量仅可从某些受试者获得时，在计算参考区间或参考区间本身的置信度时需要额外小心。

 讨论

良好的质量参考限可最大限度地减少假阳性和假阴性结果，从而最大限度地提高临床效用和患者利益。质量指标包括使用适当大小的参考数据集和适当的数值处理来进行报告；适当时使用基于主题的参考限值；对每个患者的测试仅限于有临床指征、独立且高度区分的测试。