Saudi-Specific Laboratory Reference Intervals

Accurate interpretation of laboratory test results depends on reference intervals (RIs), which define the expected range for healthy individuals. In Saudi Arabia, most laboratories rely on manufacturer-provided RIs derived from Western populations. While these may be appropriate for some analytes, genetic, environmental, and lifestyle differences can produce clinically meaningful shifts. Where Western-derived intervals do not reflect the Saudi population, their use risks diagnostic misclassification, unnecessary investigations, delayed treatment, and reduced confidence in test interpretation. Establishing Saudi-specific RIs - whether by confirming the adequacy of existing intervals or revising them where warranted - is therefore essential to improving diagnostic accuracy, clinical equity, and healthcare efficiency in alignment with Saudi Arabia’s Vision 2030 priorities.

This project will modernize RIs for Saudi Arabia using indirect estimation methods applied to large-scale real-world laboratory data. Ten years of retrospective results will be compiled from central laboratories at King Faisal Specialist Hospital and Research Centre (Riyadh, Jeddah, Madinah) and three collaborating hospitals (Dhahran, Jeddah, Aseer). The refineR algorithm will be used to derive analyte-specific RIs without recruiting new volunteers. The process will include data preprocessing, statistical decomposition of mixed populations, optimization of the “healthy” component, and stratification by age and sex where justified. Derived RIs will be compared across hospitals and benchmarked against international studies to ensure robustness.

A distinctive feature of this project is the use of employee health clinic data, where over 15 years of standardized pre-employment screening provides results from asymptomatic individuals deemed fit for work. This dataset allows application of both the direct (CLSI EP28-A3C nonparametric) and indirect (refineR) methods to the same population, enabling head-to-head validation of refineR. To strengthen cohort integrity, additional clinical screening information documented electronically (e.g., hospitalization history, medication use, tobacco/alcohol exposure, pregnancy status) will be reviewed, and individuals not meeting CLSI health criteria will be excluded (see Supplementary Information). This comparison will test whether CLSI-derived limits fall within refineR confidence intervals and provide strong evidence for indirect methods as a credible, efficient alternative to resource-intensive direct studies.

The project’s objectives are to: (1) establish Saudi-specific RIs for at least 50 common analytes, including chemistry, immunoassay, and hematology, (2) assess age- and sex-specific partitioning, (3) evaluate harmonization across hospitals, (4) benchmark against international RIs, and (5) validate refineR against CLSI EP28-A3C using employee data.

Expected outcomes include validated Saudi-specific RIs, evidence of population-specific analyte shifts, an open-access RI catalog with LIS implementation tools, and methodological publications supporting transparency and reuse. Engagement with the Ministry of Health, dissemination workshops, and processes for future updates will ensure national adoption. Exploratory health economics analyses will identify analytes with the greatest efficiency gains, informing future cost-effectiveness studies. By combining methodological innovation, rigorous validation, and translational outputs, this project will deliver a scalable framework for modernizing laboratory medicine in Saudi Arabia and directly advance Vision 2030 Health Sector Transformation Program goals.

Haifa Aldakhil, Tarek Owaidah, Khaled Alabduljabbar, Fahad Alshehri, Yahya Alghamdi, Anwar Borai, Anwar Alotaibi, Yasmin Altwaijri, Lisa Bilal, Raghad Alfulayj.