Generating method-specific Reference Ranges – A harmonious outcome?

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.