Performance and comparability of laboratory methods for measuring ferritin concentrations in human serum or plasma: A systematic review and meta-analysis

BACKGROUND: Different laboratory methods are used to quantify ferritin concentrations as a marker of iron status. A systematic review was undertaken to assess the accuracy and comparability of the most used methods for ferritin detection. METHODS AND FINDINGS: National and regional databases were searched for prospective, retrospective, sectional, longitudinal and case-control studies containing the characteristics and performance of at least one method for serum/plasma ferritin determinations in humans published to date. The analysis included the comparison between at least 2 methods detailing: sensitivity, precision, accuracy, predictive values, inter-methods adjustment, and use of international reference materials. Pooled method performance was analyzed for each method and across methods. OUTCOMES: Search strategy identified 11893 records. After de-duplication and screening 252 studies were assessed, including 187 studies in the qualitative analysis and 148 in the meta-analysis. The most used methods included radiometric, nonradiometric and agglutination assays. The overall within-run imprecision for the most reported ferritin methods was 6.2±3.4% (CI 5.69–6.70%; n = 171), between-run imprecision 8.9±8.7% (CI 7.44–10.35%; n = 136), and recovery rate 95.6% (CI 91.5–99.7%; n = 94). The pooled regression coefficient was 0.985 among all methods analyzed, and 0.984 when comparing nonradiometric and radiometric methods, without statistical differences in ferritin concentration ranging from 2.3 to 1454 μμg/L. CONCLUSION: The laboratory methods most used to determine ferritin concentrations have comparable accuracy and performance. Registered in PROSPERO CRD42016036222.