Abstract

Numerous biological variation (BV) studies have been performed over the years, but the quality of these studies vary. The objectives of this study were to perform a systematic review and critical appraisal of BV studies on glycosylated albumin and to deliver updated BV estimates for glucose and HbA1c, including recently published high-quality studies such as the European Biological Variation study (EuBIVAS). Systematic literature searches were performed to identify BV studies. Nine publications not included in a previous review were identified; four for glycosylated albumin, three for glucose, and three for HbA1c. Relevant studies were appraised by the Biological Variation Data Critical Appraisal Checklist (BIVAC). Global BV estimates were derived by meta-analysis of BIVAC-compliant studies in healthy subjects with similar study design. One study received BIVAC grade A, 2B, and 6C. In most cases, the C-grade was associated with deficiencies in statistical analysis. BV estimates for glycosylated albumin were: CVI=1.4% (1.2-2.1) and CVG=5.7% (4.7-10.6), whereas estimates for HbA1c, CVI=1.2% (0.3-2.5), CVG=5.4% (3.3-7.3), and glucose, CVI=5.0% (4.1-12.0), CVG=8.1% (2.7-10.8) did not differ from previously published global estimates. The critical appraisal and rating of BV studies according to their methodological quality, followed by a meta-analysis, generate robust, and reliable BV estimates. This study delivers updated and evidence-based BV estimates for glycosylated albumin, glucose and HbA1c.

Highlights

  • Biological variation (BV) is defined as the random fluctuation of a measurand in a biological fluid to achieve a balance between turnover and the homeostatic setting point [1,2,3]

  • The critical appraisal and rating of biological variation (BV) studies according to their methodological quality, followed by a meta-analysis, generate robust, and reliable BV estimates

  • The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group on Biological Variation (WG-BV) and the Task Group for the Biological Variation Database (TG-BVD) have undertaken several initiatives to improve the quality of available BV data, including developing a critical appraisal checklist to be applied to studies on BV, the Biological Variation Data Critical Appraisal Checklist (BIVAC) [12]

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Summary

Introduction

Biological variation (BV) is defined as the random fluctuation of a measurand in a biological fluid to achieve a balance between turnover and the homeostatic setting point [1,2,3]. The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group on Biological Variation (WG-BV) and the Task Group for the Biological Variation Database (TG-BVD) have undertaken several initiatives to improve the quality of available BV data, including developing a critical appraisal checklist to be applied to studies on BV, the Biological Variation Data Critical Appraisal Checklist (BIVAC) [12]. Applying this quality appraisal tool, the groups have been reviewing and critically appraising BV studies for a wide range of measurands and developed a meta-analysis approach to produce global BV estimates. The results of the critical reviews and meta-analysis derived global estimates for measurands associated with diabetes mellitus (DM) [13], lipids [14], and hematologic parameters [15] have recently been published

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