Transference Validation of Clinically Utilized Immunoassay Reference Intervals: Evidence From Thyroid Function–Related Hormones

Context.—: Thyroid test standardization is hindered by interplatform variability, especially for immunoassays lacking metrologic traceability. Direct method-derived reference intervals (RIs) are gold standard but resource intensive. RI transference allows cost-effective multiplatform RI establishment but necessitates balanced consideration of statistical relevance, precision, and clinical feasibility. Objectives.—: To validate an RI transference framework for harmonizing RIs across platforms, using thyroid function testing as a model for assays with inconsistent reference standards. Design.—: Dual-platform framework (Roche Cobas e601 versus Beckman DxI 800) using euthyroid community midrange specimens (n = 2423) and pathology-enriched clinical leftovers (n = 300). Weighted Deming regression (constant coefficient of variation [CV]: thyroid-stimulating hormone [TSH], free thyroxine [FT4], total triiodothyronine [TT3]) and standard Deming regression (constant standard deviation: free triiodothyronine [FT3], total thyroxine [TT4]) were applied. Precision was evaluated via multiday temporal stability and concentration-dependent Monte Carlo sample size optimization. Spearman ρ, CV(b), and absolute value of bias ratio (|BR|) were benchmarked against direct RIs. Results.—: To explore multiday sampling, weighted Deming enabled accurate TSH transfer [CV(b) = 2.07%-2.89%] and acceptable precision for FT4/TT3/TT4 [CV(b) = 5.97%-10.82%]. Randomized multiday sampling reduced extreme |BR| outliers by 51% to 89%. To compare concentration-driven data sources, community-derived specimens showed superior alignment with direct RIs (FT3: |BR| = 0.581 versus 1.161 in residuals), despite weaker correlations (ρ = 0.33 versus 0.92) at n = 40. When using community-derived specimens, FT3 exhibited persistent challenges [ρ = 0.33-0.36; CV(b) = 3.07%-23.44%] attributable to methodologic heterogeneity. To determine the adaptive sample size, optimization suggested that 45 prestratified residuals with bootstrap resampling (100 × 40 pairs) improved efficiency but introduced pathologic bias (FT3 |BR| = 1.161). Conclusions：: This study established a comprehensive thyroid testing RI transference framework integrating multiday sampling, adaptive sample size, and concentration-driven data selection, identifying optimal solutions to enable cross-platform RI establishment for immunoassays. Resource-limited laboratories can further leverage multicenter direct RIs via transference to balance cost and clinical validity.