Citation

Siegel L, Murad MH, Riley RD, Bazerbachi F, Wang Z, Chu H. Am. J. Epidemiol. 2022; ePub(ePub): ePub.

Copyright

(Copyright © 2022, Oxford University Press)

DOI

10.1093/aje/kwac013

PMID

35102410

Abstract

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 or 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 incorporate both within and between-study variations were recently proposed. In this guide, we present three approaches for estimating the reference range: a frequentist, a Bayesian, and an empirical method. Each method can be applied to either aggregate or individual participant data (IPD) meta-analysis, with the latter being the gold standard when available. We illustrate the application of these approaches to data from a previously published IPD meta-analysis evaluating the normal ranges of liver stiffness by transient elastography between 2006 and 2016.

Language: en

Keywords

meta-analysis; normative data; prediction interval; random effects; Reference range