Result harmonization in medical laboratories: accomplishments and challenges

The Joint Committee for Traceability in Laboratory Medicine (JCTLM) supports worldwide equivalence and comparability of measurement results in laboratory medicine to improve health care and facilitate national and international trade in <i>in vitro</i> diagnostic (IVD) medical devices. The 2025 biennial members and stakeholders' workshop focused on the expectations and benefits of harmonized results among medical laboratories, as well as the challenges associated with achieving this goal. Harmonization of results from end-user IVD measurement procedures (IVD-MPs) can be achieved by applying the principles of metrological traceability; however, there are several historical examples of standardization efforts that did not achieve the required level of harmonization. The reasons for these failures can be found in various elements of the calibration hierarchy including: a) an unclear definition of the measurand, b) differences in selectivity of the IVD-MPs, c) issues with the commutability characteristics of secondary certified reference materials (CRM), d) inconsistencies in handling of CRMs to prepare calibrators, and e) lack of adoption and implementation by the IVD manufacturers. The lack of harmonized results can lead to confusion, treatment delays, errors in medical decisions, and increased healthcare costs. There are still assays in common use that lack metrological traceability because they lack CRMs, reference method procedures (RMPs), and/or reference method services (RMSs). Producing and maintaining reference measurement system components is complex and expensive. There are multiple regulatory frameworks and requirements that IVD manufacturers must meet worldwide. There is a vital role for External Quality Assessment (EQA) providers to assess the agreement status of results across different IVD-MPs and identify any changes in their equivalence. However, EQA materials must be commutable with clinical samples for each of the examined IVD-MDs for results to reflect the status of harmonization of clinical sample results. The future will need leadership and cooperation between bodies such as JCTLM, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), and IVD manufacturers.