Generating method-specific Reference Ranges – A harmonious outcome?

Abstract

Objectives: When laboratory Reference Ranges (RR) do not reflect analytical methodology, result interpretation can cause misclassification of patients and inappropriate management. This can be mitigated by determining and implementing method-specific RRs, which was the main objective of this study. Design and methods: Serum was obtained from healthy volunteers (Male + Female, n > 120) attending hospital health-check sessions during June and July 2011. Pseudo-anonymised aliquots were stored (at − 70 °C) prior t° analysis on Abbott ARCHITECT c16000 chemistry and i2000SR immunoassay analysers. Data were stratified by gender where appropriate. Outliers were excluded statistically (Tukey method) to generate non-parametric RRs (2.5th + 97.5th percentiles). RRs were compared to those quoted by Abbott and UK Pathology Harmony (PH) where possible. For 7 selected tests, RRs were verified using a data mining approach. Results: For chemistry tests (n = 23), Upper or Lower Reference Limits (LRL or URL) were > 20% different from Abbott ranges in 25% of tests (11% from PH ranges) but in 38% for immunoassay tests (n = 13). RRs (mmol/L) for sodium (138−144), potassium (3.8–4.9) and chloride (102−110) were considerably narrower than PH ranges (133–146, 3.5–5.0 and 95–108, respectively). The gender difference for ferritin (M: 29–441, F: 8–193 ng/mL) was more pronounced than reported by Abbott (M: 22–275, F: 5–204 ng/mL). Verification studies showed good agreement for chemistry tests (mean [SD] difference = 0.4% [1.2%]) but less so for immunoassay tests (27% [29%]), particularly for TSH (LRL). Conclusion: Where resource permits, we advocate using method-specific RRs in preference to other sources, particularly where method bias and lack of standardisation limits RR transferability and harmonisation. Keywords: Reference Ranges, Method-specific, Harmonisation