The European Biological Variation Study (EuBIVAS): Biological Variation Data for Coagulation Markers Estimated by a Bayesian Model.

Background: For biological variation (BV) data to be safely used, data must be reliable and relevant to the population in which they are applied. We used samples from the European Biological Variation Study (EuBIVAS) to determine BV of coagulation markers by a Bayesian model robust to extreme observations and used the derived within-participant BV estimates [CVP(i)] to assess the applicability of the BV estimates in clinical practice.

Method: Plasma samples were drawn from 92 healthy individuals for 10 consecutive weeks at 6 European laboratories and analyzed in duplicate for activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, D-dimer, antithrombin (AT), protein C, protein S free, and factor VIII (FVIII).

A Bayesian Approach to Biological Variation Analysis.

Background: Biological variation (BV) data have many applications for diagnosing and monitoring disease. The standard statistical approaches for estimating BV are sensitive to "noisy data" and assume homogeneity of within-participant CV. Prior knowledge about BV is mostly ignored.

Biological variation estimates for prostate specific antigen from the European Biological Variation Study; consequences for diagnosis and monitoring of prostate cancer.

Background: Prostate-specific antigen (PSA) is central in the diagnosis of prostate cancer. However, high-quality biological variation (BV) estimates for PSA are scarce. Here BV estimates from the European Biological Variation Study (EuBIVAS) for total (tPSA), free (fPSA), conjugated PSA (cPSA), and percent free PSA (%fPSA) are provided.

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.

Within-subject biological variation of activated partial thromboplastin time, prothrombin time, fibrinogen, factor VIII and von Willebrand factor in pregnant women.

Background: During pregnancy, interpretation of results from coagulation parameters can be difficult as the physiological changes that occur may affect the biochemical parameters. The aim of this study was to describe the normal course of five coagulation parameters in healthy pregnancies, and to estimate the within-subject biological variation (CVI).

Methods: Blood samples were obtained every 4th week during pregnancy and three samples after delivery in 20 healthy women and every 4th week during a 40-week period in 19 healthy non-pregnant women.

The Biological Variation Data Critical Appraisal Checklist: A Standard for Evaluating Studies on Biological Variation.

Background: Concern has been raised about the quality of available biological variation (BV) estimates and the effect of their application in clinical practice. A European Federation of Clinical Chemistry and Laboratory Medicine Task and Finish Group has addressed this issue. The aim of this report is to () describe the Biological Variation Data Critical Appraisal Checklist (BIVAC), which verifies whether publications have included all essential elements that may impact the veracity of associated BV estimates, () use the BIVAC to critically appraise existing BV publications on enzymes, lipids, kidney, and diabetes-related measurands, and () apply metaanalysis to deliver a global within-subject BV (CV) estimate for alanine aminotransferase (ALT).

The EuBIVAS Project: Within- and Between-Subject Biological Variation Data for Serum Creatinine Using Enzymatic and Alkaline Picrate Methods and Implications for Monitoring.

Background: The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) European Biological Variation Study (EuBIVAS) has been established to deliver rigorously determined biological variation (BV) indices. EuBIVAS determined BV for serum creatinine using the enzymatic and alkaline picrate measurement methods.

Method: In total, 91 healthy individuals (38 males, 53 females; age range, 21-69 years) were bled for 10 consecutive weeks at 6 European laboratories.

Biological Variation Estimates Obtained from 91 Healthy Study Participants for 9 Enzymes in Serum.

Background: We sought to develop estimates of biological variation (BV) for 9 enzymes in blood serum as part of the European Biological Variation Study.

Methods: Ninety-one healthy study participants (38 male and 53 female, 21-69 years old) were phlebotomized in each of 10 consecutive weeks at 6 European laboratories. The same preanalytical sample-handling protocol was followed at each center before transport to San Raffaele Hospital, Milan, Italy, for analysis.

Biological variation: Evaluation of methods for constructing confidence intervals for estimates of within-person biological variation for different distributions of the within-person effect.

Background: Precise estimates of the within-person biological variation, CV, can be essential both for monitoring patients and for setting analytical performance specifications. The confidence interval, CI, may be used to evaluate the reliability of an estimate, as it is a good measure of the uncertainty of the estimated CV. The aim of the present study is to evaluate and establish methods for constructing a CI with the correct coverage probability and non-cover probability when estimating CV.

Estimates of Within-Subject Biological Variation of Protein C, Antithrombin, Protein S Free, Protein S Activity, and Activated Protein C Resistance in Pregnant Women.

Background: In pregnancy, interpretation of results from coagulation parameters can be difficult because of the procoagulant physiological changes. The aim of this study was to describe the course of 5 coagulation parameters (thrombophilia markers) in healthy pregnancies, and to estimate and compare the within-subject biological variation (CV) of these parameters in healthy pregnant and nonpregnant women.

Methods: Blood samples were obtained every 4th week during pregnancy and 3 samples after delivery in 20 healthy women and every 4th week during 40 weeks in 19 healthy nonpregnant women.

The variation in high sensitive cardiac troponin concentration during haemodialysis treatment is not similar to the biological variation observed in stable end stage renal disease patients.

Background: Cardiovascular mortality is high in end stage renal disease (ESRD). This study aimed to: (1) calculate within-week within- and between-subject biological variation (CV and CV) for hs-cTn in ESRD; (2) determine the magnitude of hs-cTn concentration changes during haemodialysis (HD) treatment; and (3) compare the CV and CV to the within and between-subject variation of cTn concentration changes during HD treatments (CV and CV).

Methods: Serum samples were collected from 20 patients before and after 10 consecutive HD treatments.

Sample collections from healthy volunteers for biological variation estimates' update: a new project undertaken by the Working Group on Biological Variation established by the European Federation of Clinical Chemistry and Laboratory Medicine.

Background: Biological variation (BV) data have many fundamental applications in laboratory medicine. At the 1st Strategic Conference of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) the reliability and limitations of current BV data were discussed. The EFLM Working Group on Biological Variation is working to increase the quality of BV data by developing a European project to establish a biobank of samples from healthy subjects to be used to produce high quality BV data.

Biological Variation: The Effect of Different Distributions on Estimated Within-Person Variation and Reference Change Values.

Background: Good estimates of within-person biological variation, CVI, are essential for diagnosing and monitoring patients and for setting analytical performance specifications. The aim of the present study was to use computer simulations to evaluate the impact of various measurement distributions on different methods for estimating CVI and reference change value (RCV).

Method: Data were simulated on the basis of 3 models for distributions of the within-person effect.

Feasibility of using self-reported patient data in a national diabetes register.

Background: In order to improve recruitment of patients to the Norwegian diabetes register for adults, a questionnaire was designed to collect data directly from patients. The main aim of this study was to assess the agreement of questionnaire data with data reported to the Register from health care personnel during routine consultations.

Methods: Patient data were obtained by sending a questionnaire with 27 of the 41 Register variables to 3714 members of the Norwegian Diabetes Association.

A checklist for critical appraisal of studies of biological variation.

Data on biological variation are used for many purposes in laboratory medicine but concern exists over the validity of the data reported in some studies. A critical appraisal checklist has been produced by a working group established by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) to enable standardised assessment of existing and future publications of biological variation data. The checklist identifies key elements to be reported in studies to enable safe accurate and effective transport of biological variation data sets across healthcare systems.

Benchmarking by HbA1c in a national diabetes quality register--does measurement bias matter?

Background: Bias in HbA1c measurement could give a wrong impression of the standard of care when benchmarking diabetes care. The aim of this study was to evaluate how measurement bias in HbA1c results may influence the benchmarking process performed by a national diabetes register.

Methods: Using data from 2012 from the Norwegian Diabetes Register for Adults, we included HbA1c results from 3584 patients with type 1 diabetes attending 13 hospital clinics, and 1366 patients with type 2 diabetes attending 18 GP offices.

Point-of-care urine albumin in general practice offices: effect of participation in an external quality assurance scheme.

Background: The Norwegian Quality Improvement of Primary Care Laboratories (Noklus) offers external quality assurance (EQA) schemes (EQASs) for urine albumin (UA) annually. This study analyzed the EQA results to determine how the analytical quality of UA analysis in general practice (GP) offices developed between 1998 (n=473) and 2012 (n=1160).

Methods: Two EQA urine samples were distributed yearly to the participants by mail.

The influence of coagulation factors on the in-treatment biological variation of international normalized ratio for patients on warfarin.

Background: Biological variation is usually estimated in healthy individuals during steady-state conditions. The aim of this study was to estimate the in-treatment biological variation of the International normalised ratio (INR) and to investigate to what extent the different levels of coagulation factors could explain this variation.

Methods: Blood samples were collected from randomly included patients on warfarin treatment.

Weekly and 90-minute biological variations in cardiac troponin T and cardiac troponin I in hemodialysis patients and healthy controls.

Background: Myocardial infarction (MI) is diagnosed by the finding of a single cardiac troponin value above the 99th percentile and a significant time-dependent change in cardiac troponin concentration. The aim of this study was to determine the 90-min and weekly biological variations, the reference change value (RCV), and the index of individuality (II) of high-sensitivity cardiac troponin T (hs-cTnT) (Roche Diagnostics) and hs-cTnI (Abbott Diagnostics) in patients receiving hemodialysis (HD) and in healthy individuals.

Method: Blood samples were collected from 19 HD patients (on an HD-free day) and 20 healthy individuals at 90-min intervals over a 6-h period (between 08:30 and 14:30) and before the midweek HD treatment for 10 weeks.

A systematic review of data on biological variation for alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transferase.

Background: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT) are enzymes measured in serum or plasma to investigate liver disease. The aim of this work is to assess the validity of published biological variation (BV) data currently available for these enzymes.

Methods: Publications containing BV data for ALT, AST and GGT were identified by searching PubMed using the following keywords: biological varia*, RCV, CV(w), CV(i), CV(b), and CV(g).