Reference Intervals Revisited: A Novel Model for Population-Based Reference Intervals, Using a Small Sample Size and...

Area of Science:

• Clinical Chemistry
• Hematology
• Biostatistics

Background:

• Conventional population-based reference intervals (popRIs) rely on large sample sizes (≥120 individuals).
• Establishing accurate popRIs is crucial for interpreting laboratory test results.

Purpose of the Study:

• To explore a novel model for popRIs utilizing biological variation (BV) data.
• To compare BV-based popRIs with conventional popRIs using varying sample sizes.

Main Methods:

• A BV-based model was developed using population set point (PSP) and total variation (BV + analytical variation).
• BV-based popRIs were calculated for 48 measurands using sample sizes of n=16, n=30, and n=120.
• Simulation studies estimated the minimum number of reference individuals required.

Main Results:

• The median ratio of BV-based to conventional RI ranges was 0.98.
• BV-based popRIs were similar across different sample sizes and generally met the 90% coverage criterion.
• Fewer individuals were needed to estimate the PSP for most measurands compared to conventional methods.

Conclusions:

• The BV-based popRI model yields robust reference intervals for most measurands.
• This model requires a smaller reference group than conventional popRIs.
• Implementation is feasible with reliable biological variation data.