The biological variation of insulin resistance markers: data from the European Biological Variation Study (EuBIVAS).

Objectives: An insulin resistant state is characteristic of patients with type 2 diabetes, polycystic ovary syndrome, and metabolic syndrome. Identification of insulin resistance (IR) is most readily achievable using formulae combining plasma insulin and glucose results. In this study, we have used data from the European Biological Variation Study (EuBIVAS) to examine the biological variability (BV) of IR using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and the Quantitative Insulin sensitivity Check Index (QUICKI).

A standard to report biological variation data studies - based on an expert opinion.

There is a need for standards for generation and reporting of Biological Variation (BV) reference data. The absence of standards affects the quality and transportability of BV data, compromising important clinical applications. To address this issue, international expert groups under the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) have developed an online resource (https://tinyurl.

Analytical performance specifications based on biological variation data - considerations, strengths and limitations.

Analytical performance specifications (APS) are typically established through one of three models: (i) outcome studies, (ii) biological variation (BV), or (iii) state-of-the-art. Presently, The APS can, for most measurands that have a stable concentration, be based on BV. BV based APS, defined for imprecision, bias, total allowable error and allowable measurement uncertainty, are applied to many different processes in the laboratory.

The European biological variation study (EuBIVAS): Biological variation data for testosterone, follicle stimulating hormone, prolactin, luteinizing hormone and dehydroepiandrosterone sulfate in men.

Background: Knowledge of biological variation (BV) of hormones is essential for interpretation of laboratory tests and for diagnostics of endocrinological and reproductive diseases. There is a lack of robust BV data for many hormones in men.

Methods: We used serum samples collected weekly over 10 weeks from the European Biological Variation Study (EuBIVAS) to determine BV of testosterone, follicle-stimulating hormone (FSH), prolactin, luteinizing hormone (LH) and dehydroepiandrosterone sulfate (DHEA-S) in 38 men.

Biological variation of inflammatory and iron metabolism markers in high-endurance recreational athletes; are these markers useful for athlete monitoring?

Objectives: To deliver biological variation (BV) data for serum hepcidin, soluble transferrin receptor (sTfR), erythropoietin (EPO) and interleukin 6 (IL-6) in a population of well-characterized high-endurance athletes, and to evaluate the potential influence of exercise and health-related factors on the BV.

Methods: Thirty triathletes (15 females) were sampled monthly (11 months). All samples were analyzed in duplicate and BV estimates were delivered by Bayesian and ANOVA methods.

Critical review and meta-analysis of biological variation estimates for tumor markers.

Objectives: Biological variation data (BV) can be used for different applications, but this depends on the availability of robust and relevant BV data. In this study, we aimed to summarize and appraise BV studies for tumor markers, to examine the influence of study population characteristics and concentrations on BV estimates and to discuss the applicability of BV data for tumor markers in clinical practice.

Methods: Studies reporting BV data for tumor markers related to gastrointestinal, prostate, breast, ovarian, haematological, lung, and dermatological cancers were identified by a systematic literature search.

Long-term within- and between-subject biological variation of 29 routine laboratory measurands in athletes.

Objectives: Within- and between-subject biological variation (BV) estimates have many applications in laboratory medicine. However, robust high-quality BV estimates are lacking for many populations, such as athletes. This study aimed to deliver BV estimates of 29 routine laboratory measurands derived from a Biological Variation Data Critical Appraisal Checklist compliant design in a population of high-endurance athletes.

Biological variation estimates of thyroid related measurands - meta-analysis of BIVAC compliant studies.

Objectives: Testing for thyroid disease constitutes a high proportion of the workloads of clinical laboratories worldwide. The setting of analytical performance specifications (APS) for testing methods and aiding clinical interpretation of test results requires biological variation (BV) data. A critical review of published BV studies of thyroid disease related measurands has therefore been undertaken and meta-analysis applied to deliver robust BV estimates.

A New Electrochemiluminescence-Based Multiplex Assay for the Assessment of Human Antibody Responses to Bordetella pertussis Vaccines.

Introduction: Commercially available enzyme-linked immunosorbent assay (ELISA) kits designed for pertussis diagnostic purposes are frequently used to assess antibody responses to pertussis vaccines in clinical trials, but have limited accuracy and are not calibrated against international standards. We developed a new electrochemiluminescence (ECL)-based multiplexed assay and compared its performance to two commercial Bordetella pertussis ELISA kits and to historical in-house ELISAs.

Methods: The ECL assay quantifies serum concentrations of antibodies against four B.

The European Biological Variation Study (EuBIVAS): a summary report.

Biological variation (BV) data have many important applications in laboratory medicine. Concerns about quality of published BV data led the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) 1st Strategic Conference to indicate need for new studies to generate BV estimates of required quality. In response, the EFLM Working Group on BV delivered the multicenter European Biological Variation Study (EuBIVAS).

Within- and between-subject biological variation data for tumor markers based on the European Biological Variation Study.

Objectives: Reliable biological variation (BV) data are required for the clinical use of tumor markers in the diagnosis and monitoring of treatment effects in cancer. The European Biological Variation Study (EuBIVAS) was established by the EFLM Biological Variation Working Group to deliver BV data for clinically important measurands. In this study, EuBIVAS-based BV estimates are provided for cancer antigen (CA) 125, CA 15-3, CA 19-9, carcinoembryonic antigen, cytokeratin-19 fragment, alpha-fetoprotein and human epididymis protein 4.

Personalising laboratory medicine in the 'real world': Assessing clinical utility, by clinical indication, of serum total B and Active-B® (holotranscobalamin) in the diagnosis of vitamin B deficiency.

Background: Assessing the pre- and post-test probability of disease in the context of routine health care is challenging. We wished to study how test performance parameters relating to clinical utility vary by clinical indication in a 'real-world' setting.

Methods: The diagnostic accuracy of serum total B and Active-B® (holotranscobalamin) was evaluated in a primary care population, using serum methylmalonic acid as the reference standard.

Biological Variation of Cardiac Troponins in Health and Disease: A Systematic Review and Meta-analysis.

Background: Many studies have assessed the biological variation (BV) of cardiac-specific troponins (cTn), reporting widely varying within-subject BV (CVI) estimates. The aim of this study was to provide meta-analysis-derived BV estimates for troponin I (cTnI) and troponin T (cTnT) for different sampling intervals and states of health.

Methods: Relevant studies were identified by a systematic literature search.

Critical appraisal and meta-analysis of biological variation estimates for kidney related analytes.

Objectives: Kidney markers are some of the most frequently used laboratory tests in patient care, and correct clinical decision making depends upon knowledge and correct application of biological variation (BV) data. The aim of this study was to review available BV data and to provide updated BV estimates for the following kidney markers in serum and plasma; albumin, creatinine, cystatin C, chloride, potassium, sodium and urea.

Content: Relevant studies were identified from a historical BV database as well as by systematic literature searches.

Estimation of Instantaneous Oxygen Uptake During Exercise and Daily Activities Using a Wearable Cardio-Electromechanical and Environmental Sensor.

Objective: To estimate instantaneous oxygen uptake VO with a small, low-cost wearable sensor during exercise and daily activities in order to enable monitoring of energy expenditure (EE) in uncontrolled settings. We aim to do so using a combination of seismocardiogram (SCG), electrocardiogram (ECG) and atmospheric pressure (AP) signals obtained from a minimally obtrusive wearable device.

Methods: In this study, subjects performed a treadmill protocol in a controlled environment and an outside walking protocol in an uncontrolled environment.

Systematic review and meta-analysis of within-subject and between-subject biological variation estimates of 20 haematological parameters.

Background Interpretation of the complete blood count (CBC) parameters requires reliable biological variation (BV) data. The aims of this study were to appraise the quality of publications reporting BV data for CBC parameters by applying the BV Data Critical Appraisal Checklist (BIVAC) and to deliver global BV estimates based on BIVAC compliant studies. Methods Relevant publications were identified by a systematic literature search and evaluated for their compliance with the 14 BIVAC criteria, scored as A, B, C or D, indicating decreasing compliance.

European Biological Variation Study (EuBIVAS): Within- and Between-Subject Biological Variation Data for 15 Frequently Measured Proteins.

Background: The European Biological Variation Study (EuBIVAS) was established to deliver rigorously determined data for biological variation (BV). Here, EuBIVAS-based BV estimates are provided for α-acid glycoprotein, α-antitrypsin, albumin, β-microglobulin, ceruloplasmin, complement component 3, complement component 4, C-reactive protein (CRP), cystatin C, haptoglobin, IgA, IgG, IgM, soluble transferrin receptor (sTfR), and transferrin (Trf), together with their associated analytical performance specifications (APSs) and reference change values (RCVs).

Method: Serum samples from weekly blood samplings of 91 healthy study participants (38 males and 53 females, ages 21-69 years old) over 10 consecutive weeks in 6 European laboratories were stored at -80 °C before duplicate analysis on a Roche Cobas c702.

Biological variation data for lipid cardiovascular risk assessment biomarkers. A systematic review applying the biological variation data critical appraisal checklist (BIVAC).

Background: Biological variation (BV) data can be used to set analytical performance specifications (APS) for lipid assays. Poor performance will impact upon the efficacy of international guidelines for cardiovascular risk assessment (CVR) and relevant clinical decision limits. This systematic review applies the Biological Variation Data Critical Appraisal Checklist (BIVAC) to published studies of BV of CVR biomarkers enabling metanalysis of the data.

Systematic review of the biological variation data for diabetes related analytes.

Background: Objective interpretation of laboratory test results used to diagnose and monitor diabetes mellitus in part requires the application of biological variation data (BVD). The quality of published BVD has been questioned. The aim of this study was to quality assess publications reporting BVD for diabetes-related analytes using the Biological Variation Data Critical Appraisal Checklist (BIVAC); to assess whether published BVD are fit for purpose and whether the study design and population attributes influence BVD estimates and to undertake a meta-analysis of the BVD from BIVAC-assessed publications.

Development and validation of diagnostic triage criteria for liver disease from a minimum data set enabling the 'intelligent LFT' pathway for the automated assessment of deranged liver enzymes.

Background: Liver function tests (LFTs) are commonly abnormal; most patients with 'incidental' abnormal LFTs are not investigated appropriately and for those who are, current care pathways are geared to find an explanation for the abnormality by a lengthy process of investigation and exclusion, with costs to the patient and to the health service.

Objective: To validate an intelligent automatable analysis tool (iLFT) for abnormal liver enzymes, which diagnoses common liver conditions, provides fibrosis stage and recommends management.

Design: A retrospective case note review from three tertiary referral liver centres, with application of the iLFT algorithm and comparison with the clinician's final opinion as gold standard.

The EuBIVAS: Within- and Between-Subject Biological Variation Data for Electrolytes, Lipids, Urea, Uric Acid, Total Protein, Total Bilirubin, Direct Bilirubin, and Glucose.

Background: The European Federation of Clinical Chemistry and Laboratory Medicine European Biological Variation Study (EuBIVAS) has been established to deliver rigorously determined data describing biological variation (BV) of clinically important measurands. Here, EuBIVAS-based BV estimates of serum electrolytes, lipids, urea, uric acid, total protein, total bilirubin, direct bilirubin, and glucose, as well as their associated analytical performance specifications (APSs), are presented.

Method: Samples were drawn from 91 healthy individuals (38 male, 53 female; age range, 21-69 years) for 10 consecutive weeks at 6 European laboratories.