A-203 Biological variation reference data; EFLM initiatives and developments to address data quality issues and deliver reliable data.

Abstract

Biological variation data (BVD), which describes within-subject (CVI) and between-subject (CVG) variability of laboratory measurands, are essential reference data in laboratory medicine. BVD are used to define analytical performance specifications (APS) for imprecision, bias, maximum allowable measurement uncertainty, and allowable total error limits (ATE). Other quality-related applications include definition of reference change values and indices of individuality. The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) identified concerns about the quality of published BVD at its 1st Strategic Conference in Milan in 2014. As a result, EFLM launched initiatives to improve access, quality, and understanding of BVD. The objectives were to:Enable access to BVD that is transportable as reference data.Assess and improve BVD quality through standards development.Promote user knowledge and understanding of biological variation and BVD applications. The EFLM assembled international expert groups to address these objectives. Their approach included:Critical appraisal of published BVD studies enabling development of tools for objective quality assessment and grading of both historical and new BVD studies.Coordination and delivery of exemplar studies to produce high-quality BVD.Identification of a minimum data set to accompany BVD reference data.Creation of an online database of quality-assessed BVD.Definition of standards for reporting new BVD studiesGeneration of a knowledge base to raise awareness of BVD issues through presentations and publications. The task forces and committees focused on the issues, to address the objectives enabling quality and confidence concerns around BVD to be identified and addressed. EFLM’s work has led to the following achievements:Biological Variation Data Critical Appraisal Checklist (BIVAC): A tool to assign quality grades (A–D) to studies (https://academic.oup.com/clinchem/article-abstract/64/3/501/5608807?redirectedFrom=fulltext).EFLM BV Database and Website: A curated online resource containing BVD estimates with detailed metadata, BIVAC scores, meta-analyses, automatic APS, and reference change value calculations. The latest version (2026), available at https://biologicalvariation.eu/, offers improved user experience and access to over 3,250 biological data sets from nearly 600 published articles. There are also more than 190 meta-analysis derived global biological variation estimates published on the site, each delivering improved point estimates with tighter confidence limits.EuBIVAS Study: An exemplar BIVAC grade “A” European study providing new BVD (https://www.degruyter.com/document/doi/10.1515/cclm-2021-0370/html).Knowledge Base: Over 40 peer-reviewed articles reporting new BVD, reviews, and critical appraisals (https://www.eflm.eu/site/pubsearch/WG-BV;C-BV).STARBIV Standard: A framework for reporting BVD studies is embedded into the website in the form of an interactive mind map. STARBIV is recognized by the EQUATOR network as a reporting standard (https://www.equator-network.org/reporting-guidelines/starbiv-a-standard-to-report-biological-variation-data-studies/). High-quality BVD are essential reference data required for laboratory medicine delivery and patient care. EFLM’s efforts to develop tools, standards, and databases address historical gaps and support future innovations, including data mining and personalized reference intervals. The latest 2026 iteration of the EFLM Biological Variation Database web site makes available a rich source of critically assessed biological variation data, alongside tools, information and knowledge to support the safe and effective application of biological variation reference data.