Siegel, L, Murad, MH, Riley, RD, Bazerbachi, F, Wang, Z and Chu, H (2022) A Guide to Estimating the Reference Range From a Meta-Analysis Using Aggregate or Individual Participant Data. American Journal of Epidemiology, 191 (5). 948 - 956. ISSN 1476-6256

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Clinicians frequently must decide whether a patient's measurement reflects that of a healthy "normal" individual. Thus, the reference range is defined as the interval in which some proportion (frequently 95%) of measurements from a healthy population is expected to fall. One can estimate it from a single study or preferably from a meta-analysis of multiple studies to increase generalizability. This range differs from the confidence interval for the pooled mean and the prediction interval for a new study mean in a meta-analysis, which do not capture natural variation across healthy individuals. Methods for estimating the reference range from a meta-analysis of aggregate data that incorporates both within- and between-study variations were recently proposed. In this guide, we present 3 approaches for estimating the reference range: one frequentist, one Bayesian, and one empirical. Each method can be applied to either aggregate or individual-participant data meta-analysis, with the latter being the gold standard when available. We illustrate the application of these approaches to data from a previously published individual-participant data meta-analysis of studies measuring liver stiffness by transient elastography in healthy individuals between 2006 and 2016.

Item Type: Article
Additional Information: © The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (
Subjects: R Medicine > R Medicine (General)
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Depositing User: Symplectic
Date Deposited: 04 Aug 2022 09:50
Last Modified: 01 Feb 2023 01:30

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