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A Parametric Empirical Bayes Approach to Personalized Reference Intervals and Reference Change Values.

Eirik Åsen Røys1,2, Kristin Viste1,2, Christopher-John Farrell3

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Personalized reference intervals (RIper) improve diagnostic precision by accounting for individual variability. The parametric empirical Bayes (PEB) framework enables reliable RIper using population data, even with limited individual results.

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Area of Science:

  • Laboratory medicine
  • Biomarker analysis
  • Personalized diagnostics

Background:

  • Population-wide reference intervals (RIpop) may not reflect individual homeostatic ranges.
  • Personalized reference intervals (RIper) can enhance diagnostic precision.
  • A parametric empirical Bayes (PEB) framework stabilizes individual estimates for reliable RIper.

Purpose of the Study:

  • To apply the PEB framework for estimating RIper for nine key biomarkers.
  • To compare PEB-based RIper with conventional RIpop and reference change values (RCVs).
  • To assess the feasibility of using routine Laboratory Information System (LIS) or biological variation (BV) data for PEB parameter establishment.

Main Methods:

  • Applied the PEB framework to estimate RIper for albumin, creatinine, phosphate, cortisone, cortisol, testosterone, androstenedione, 17-hydroxyprogesterone, and 11-deoxycortisol.
  • Derived PEB parameters from LIS data and a local BV study.
  • Assessed flagged results and compared RIper to RIpop and RCVs using serial samples from healthy adults.

Main Results:

  • PEB-based RIper were consistently narrower than RIpop, reducing flagged results for albumin, phosphate, and cortisone.
  • Flagging for 17-hydroxyprogesterone increased but remained close to the expected 5%.
  • PEB thresholds corrected for regression toward the mean, proving narrower than standard RCV estimates without increasing flagged results.

Conclusions:

  • The PEB framework effectively generates personalized cutoffs for laboratory tests, even with limited individual data.
  • PEB parameters can be derived from LIS or BV data, indicating a feasible implementation pathway.
  • This approach offers a cost-effective method for enhancing diagnostic precision through personalized reference intervals.