Background Conventional population-based reference intervals (popRIs) are established on the ranking of single measurement results from at least 120 reference individuals. In this study, we aimed to explore a new model for popRIs, utilizing biological variation (BV) data to define the reference interval (RI) limits and compared BV-based popRI from different sample sizes with previously published conventional popRIs from the same population. Methods The model is based on defining the population set point (PSP) from single-measurement results of a group of reference individuals and using the total variation around the PSP, derived from the combination of BV and analytical variation, to define the RI limits. Using data from 143 reference individuals for 48 clinical chemistry and hematology measurands, BV-based popRIs were calculated for different sample sizes (n = 16, n = 30, and n = 120) and considered acceptable if they covered 90% of the population. In addition, simulation studies were performed to estimate the minimum number of required reference individuals. Results The median ratio of the BV-based to conventional RI ranges was 0.98. The BV-based popRIs calculated from the different samples were similar, and most met the coverage criterion. For 25 measurands ≤16 reference individuals and for 23 measurands >16 reference individuals were required to estimate the PSP. Conclusions The BV-based popRI model delivered robust RIs for most of the included measurands. This new model requires a smaller group of reference individuals than the conventional popRI model and can be implemented if reliable BV data are available.

中文翻译：

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重新审视参考区间：使用小样本量和生物变异数据进行基于人群的参考区间的新模型


背景 传统的基于人群的参考区间 （popRI） 是根据至少 120 个参考个体的单个测量结果的排名建立的。在这项研究中，我们旨在探索 popRI 的新模型，利用生物变异 （BV） 数据来定义参考区间 （RI） 限制，并将来自不同样本量的基于 BV 的 popRI 与先前发表的来自同一人群的常规 popRI 进行比较。方法 该模型基于从一组参考个体的单次测量结果中定义群体设定点 （PSP），并使用 PSP 周围的总变异（从 BV 和分析变异的组合得出）来定义 RI 限值。使用来自 48 个临床化学和血液学测量对象的 143 个参考个体的数据，针对不同的样本量（n = 16、n = 30 和 n = 120）计算基于 BV 的 popRIs，如果它们覆盖了 90% 的人群，则认为它们是可以接受的。此外，还进行了模拟研究以估计所需的参考个体的最小数量。结果 基于 BV 的 RI 范围与常规 RI 范围的中位数比值为 0.98。从不同样本计算的基于 BV 的 popRI 相似，并且大多数都符合覆盖率标准。对于 25 个被测变量 ≤16 个参考个体和 23 个被测变量 >16 个参考个体，需要估计 PSP。结论基于 BV 的 popRI 模型为大多数包含的被测对象提供了强大的 RI。与传统的 popRI 模型相比，这种新模型需要更小的参考个体组，并且在有可靠的 BV 数据可用时可以实施。