Estimating the reference range from a meta-analysis

Lianne Siegel, M. Hassan Murad, Haitao Chu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Often clinicians are interested in determining whether a subject's measurement falls within a normal range, defined as a range of values of a continuous outcome which contains some proportion (eg, 95%) of measurements from a healthy population. Several studies in the biomedical field have estimated reference ranges based on a meta-analysis of multiple studies with healthy individuals. However, the literature currently gives no guidance about how to estimate the reference range of a new subject in such settings. Instead, meta-analyses of such normative range studies typically report the pooled mean as a reference value, which does not incorporate natural variation across healthy individuals in different studies. We present three approaches to calculating the normal reference range of a subject from a meta-analysis of normally or lognormally distributed outcomes: a frequentist random effects model, a Bayesian random effects model, and an empirical approach. We present the results of a simulation study demonstrating that the methods perform well under a variety of scenarios, though users should be cautious when the number of studies is small and between-study heterogeneity is large. Finally, we apply these methods to two examples: pediatric time spent awake after sleep onset and frontal subjective postural vertical measurements.

Original languageEnglish (US)
Pages (from-to)148-160
Number of pages13
JournalResearch Synthesis Methods
Issue number2
StatePublished - Mar 2021


  • meta-analysis
  • normative data
  • prediction interval
  • random effects model
  • reference range

ASJC Scopus subject areas

  • Education


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