en Cardiovascular Diseases Cardiovascular Diseases نامه به سردبیر Letter to editor <span style="font-size:9pt"><span minion="" pro="" style="font-family:"><b>Background</b>: Distinguishing true pathological changes from normal physiological fluctuation in serial laboratory results are fundamental to personalized medicine. Biological variation (BV)-comprising within-subject (CVI) and between-subject (CVG) variations- provides the statistical foundation for calculating reference change values (RCVs), establishing analytical performance specifications (APS), and interpreting patient-specific trends. However, historical BV data have been plagued by methodological heterogeneity, small sample sizes, and inadequate preanalytical standardization.</span></span><br> <span style="font-size:9pt"><span minion="" pro="" style="font-family:"><b>Content</b>: The European Biological Variation Study (EuBIVAS) was conceived as a landmark prospective multicenter investigation to address these deficiencies. Enrolling 91 apparently healthy adults across six European centers, EuBIVAS implemented weekly blood sampling for 10 consecutive weeks under strictly harmonized conditions. To date, this ambitious project has generated high-quality, in accordance with Biological Variation Data Critical Appraisal Checklist (BIVAC) -compliant BV estimates for over 80 measurands- including routine chemistry analytes, enzymes, proteins, endocrine biomarkers, tumor markers, cardiac troponin I, hematological parameters, bone markers, serum iron, and insulin-resistance indices. Notably, EuBIVAS has provided the first-ever BV data for ten measurands, including non-HDL cholesterol, neuron-specific enolase, and intact fibroblast growth factor-23.</span></span><br> <span style="font-size:9pt"><span minion="" pro="" style="font-family:"><b>Editorial perspective</b>: EuBIVAS represents a paradigm shift in BV research, establishing a new methodological gold standard. Nevertheless, critical appraisal reveals important limitations: the small postmenopausal subgroup (n=10) limits reliable sex-stratified analyses; the classical Cross-Validated Analysis of Variance (CV-ANOVA) model proved inadequate for non-steady-state measurands such as 25-hydroxyvitamin D; and the exclusive focus on healthy European adults restricts generalizability to pediatric, geriatric, and diverse ethnic populations.</span></span><br> <span style="font-size:9pt"><span minion="" pro="" style="font-family:"><b>Conclusions</b>: EuBIVAS provides a strong foundation for the interpretation of serial laboratory testing. Further studies in diverse demographic and clinical populations, as well as practical implementation in laboratory information systems, are necessary to maximize its clinical value. Although, EuBIVAS is not the final word on biological variation, however, it is an essential foundation for the future of clinical biochemistry and personalized laboratory medicine.</span></span> Biological variation, Reference change value, Analytical performance specifications, Laboratory medicine, Index of individuality 1 9 http://jbrms.medilam.ac.ir/browse.php?a_code=A-10-330-16&slc_lang=en&sid=1 Ali Noori-Zadeh alincbc@gmail.com 10031947532846008548 10031947532846008548 Yes Department of Clinical Biochemistry, Faculty of Medicine, Ilam University Medical Sciences, Ilam, Iran