Personalized reference intervals for biochemical, hormonal, and coagulation tests: Comparison with population-based reference intervals.
Level 3 - non-randomized controlled study
Prospective longitudinal observational study tracking repeated measures over time in a healthy cohort.
PubMed 42419667 · doi:10.1016/j.cca.2026.121220
What was done
Forty-five healthy adults (28 females, 17 males) underwent weekly blood sampling for six weeks. Analytical variation, within-subject variation, and between-subject components were estimated following European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) guidelines. Personalized reference intervals (prRIs) were calculated and compared against population-based reference intervals (popRIs) across clinical chemistry, hormone, and coagulation analytes using the index of individuality (II) and reference interval index (RII).
What was found
Personalized reference intervals were generally narrower than population reference intervals, with 94.7% of RII values <1. High individuality (II <0.6), indicating poor suitability of population-based intervals, was observed for liver enzymes (ALT, AST, LDH, GGT, ALP), albumin, creatinine, ferritin, lipids, and thyroid hormones (TSH, FT4). Coagulation tests also yielded narrower prRIs. In contrast, serum iron showed low individuality (II >1.4), supporting standard population-based intervals. Zinc and prolactin showed broader prRIs in select participants, and creatine kinase displayed high within-subject variability.
Why it matters
Standard population reference intervals can mask clinically relevant intra-individual shifts in serial laboratory testing. These findings delineate which measurands benefit most from individualized reference ranges versus standard population cutoffs.
Limits
The study evaluated a small sample of 45 healthy participants over a brief six-week window, which may not capture long-term seasonal or physiological shifts. The cohort excluded individuals with acute or chronic diseases, and the study did not measure clinical outcomes to establish whether using prRIs alters diagnostic accuracy or patient care.
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- supports Standard clinical laboratory reference ranges for biomarkers like cholesterol, glucose, and sodium are determined based on population averages rather than individualized baselines.