Study Of Biological Variation Research Articles

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

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. Subjects from five European countries were enrolled in the study, and weekly samples were collected from 91 healthy individuals (53 females and 38 males; 21-69 years old) for 10 consecutive weeks. All samples were analyzed in duplicate within a single run. After excluding outliers and homogeneity analysis, the BVs of tumor markers were determined by CV-ANOVA on trend-corrected data, when relevant (Røraas method). Marked individuality was found for all tumor markers. CYFRA 21-1 was the measurand with the highest index of individuality (II) at 0.67, whereas CA 19-9 had the lowest II at 0.07. The CV I s of HE4, CYFRA 21-1, CA 19-9, CA 125 and CA 15-3 of pre- and postmenopausal females were significantly different from each other. This study provides updated BV estimates for several tumor markers, and the findings indicate that marked individuality is characteristic. The use of reference change values should be considered when monitoring treatment of patients by means of tumor markers.

European Biological Variation Study (EuBIVAS): within- and between-subject biological variation estimates for serum thyroid biomarkers based on weekly samplings from 91 healthy participants.

Thyroid biomarkers are fundamental for the diagnosis of thyroid disorders and for the monitoring and treatment of patients with these diseases. The knowledge of biological variation (BV) is important to define analytical performance specifications (APS) and reference change values (RCV). The aim of this study was to deliver BV estimates for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroglobulin (TG), and calcitonin (CT). Analyses were performed on serum samples obtained from the European Biological Variation Study population (91 healthy individuals from six European laboratories; 21-69 years) on the Roche Cobas e801 at the San Raffaele Hospital (Milan, Italy). All samples from each individual were evaluated in duplicate within a single run. The BV estimates with 95% CIs were obtained by CV-ANOVA, after analysis of variance homogeneity and outliers. The within-subject (CV I ) BV estimates were for TSH 17.7%, FT3 5.0%, FT4 4.8%, TG 10.3, and CT 13.0%, all significantly lower than those reported in the literature. No significant differences were observed for BV estimates between men and women. The availability of updated, in the case of CT not previously published, BV estimates for thyroid markers based on the large scale EuBIVAS study allows for refined APS and associated RCV applicable in the diagnosis and management of thyroid and related diseases.

Identifying adaptive alleles in the human genome: from selection mapping to functional validation.

The suite of phenotypic diversity across geographically distributed human populations is the outcome of genetic drift, gene flow, and natural selection throughout human evolution. Human genetic variation underlying local biological adaptations to selective pressures is incompletely characterized. With the emergence of population genetics modeling of large-scale genomic data derived from diverse populations, scientists are able to map signatures of natural selection in the genome in a process known as selection mapping. Inferred selection signals further can be used to identify candidate functional alleles that underlie putative adaptive phenotypes. Phenotypic association, fine mapping, and functional experiments facilitate the identification of candidate adaptive alleles. Functional investigation of candidate adaptive variation using novel techniques in molecular biology is slowly beginning to unravel how selection signals translate to changes in biology that underlie the phenotypic spectrum of our species. In addition to informing evolutionary hypotheses of adaptation, the discovery and functional annotation of adaptive alleles alsomay be of clinical significance. While selection mapping efforts in non-European populations are growing, there remains a stark under-representation of diverse human populations in current public genomic databases, of both clinical and non-clinical cohorts. This lack of inclusion limits the study of human biological variation. Identifying and functionally validating candidate adaptive alleles in more global populations is necessary for understanding basic human biology and human disease.

European Biological Variation Study (EuBIVAS): within- and between-subject biological variation estimates for serum biointact parathyroid hormone based on weekly samplings from 91 healthy participants.

The European Biological Variation Study (EuBIVAS) was created by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group on Biological Variation to establish high-quality biological variation (BV) estimates for clinically important measurands. In this study, the aim was to deliver reliable BV estimates for the biointact parathyroid hormone (PTH 1-84). Serum samples were obtained from a population of 91 healthy individuals (38 men, 43 pre-menopausal women, and 10 post-menopausal women; 21-69 years) from 5 European countries, with all samples stored at -80 °C prior to analysis. PTH 1-84 analysis was performed at the San Raffaele Hospital (Milan, Italy) on the Roche Cobas e801. All samples from each individual were analysed in duplicate within a single run. CV-ANOVA was applied, after analysis of variance homogeneity and outliers, to obtain BV estimates for PTH 1-84 with 95% CIs. The within-subject BV [CVI (95% CI)] estimates were significantly different between men and women [13.0% (12.1-14.2%) and 15.2% (14.3-16.3%), respectively], while the between-subject estimates [CVG (95% CI)] were similar (men: 26.8% (21.4-35.1%), pre-menopausal women: 27.8% (22.7-36.1%)], allowing for delivery of updated analytical performance specifications and reference change values. Updated BV estimates for serum PTH 1-84 based on the large-scale EuBIVAS may be beneficial for the diagnosis and management of parathyroid glands and bone turnover pathologies.

Impact of Artificial Diet on Development and Coloration in Zerene Cesonia

The development of artificial diets for Lepidopteran species is instrumental for the study of natural biological variation in controlled laboratory conditions. In this study, we test the ability to rear Zerene cesonia, a pierid species, on artificial diets containing varying amounts of two plant species: Dalea purpurea and Trifolium pratense. We evaluate the quality of each diet based on survivorship, developmental timing, and analyses of larval and adult coloration. This study concludes that diets that include the preferred host plant, D. purpurea, are best for rearing Z. cesonia based on survivorship and the ability to recapitulate the natural color variation observed in the wild.

Critical appraisal and meta-analysis of biological variation studies on glycosylated albumin, glucose and HbA1c.

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.

The European Biological Variation Study (EuBIVAS): weekly biological variation of cardiac troponin I estimated by the use of two different high-sensitivity cardiac troponin I assays.

Background Cardiac troponins (cTn) are specific markers for cardiac damage and acute coronary syndromes. The availability of new high-sensitivity assays allows cTn detection in healthy people, thus permitting the estimation of biological variation (BV) of cTn. The knowledge of BV is important to define analytical performance specifications (APS) and reference change values (RCVs). The aim of this study was to estimate the within- and between-subject weekly BV (CVI, CVG) of cTnI applying two high-sensitivity cTnI assays, using European Biological Variation Study (EuBIVAS) specimens. Methods Thirty-eight men and 53 women underwent weekly fasting blood drawings for 10 consecutive weeks. Duplicate measurements were performed with Singulex Clarity (Singulex, USA) and Siemens Atellica (Siemens Healthineers, Germany). Results cTnI was measurable in 99.4% and 74.3% of the samples with Singulex and Atellica assays, respectively. Concentrations were significantly higher in men than in women with both methods. The CVI estimates with 95% confidence interval (CI) were for Singulex 16.6% (15.6-17.7) and for Atellica 13.8% (12.7-15.0), with the observed difference likely being caused by the different number of measurable samples. No significant CVI differences were observed between men and women. The CVG estimates for women were 40.3% and 36.3%, and for men 65.3% and 36.5% for Singulex and Atellica, respectively. The resulting APS and RCVs were similar for the two methods. Conclusions This is the first study able to estimate cTnI BV for such a large cohort of well-characterized healthy individuals deriving objective APS and RCV values for detecting significant variations in cTnI serial measurements, even within the 99th percentile.

European Biological Variation Study (EuBIVAS): within- and between-subject biological variation estimates of β-isomerized C-terminal telopeptide of type I collagen (β-CTX), N-terminal propeptide of type I collagen (PINP), osteocalcin, intact fibroblast growth factor 23 and uncarboxylated-unphosphorylated matrix-Gla protein-a cooperation between the EFLM Working Group on Biological Variation and the International Osteoporosis Foundation-International Federation of Clinical Chemistry Committee on Bone Metabolism.

Within-subject (CVI) and between-subject (CVG) biological variation (BV) estimates are essential in determining both analytical performance specifications (APS) and reference change values (RCV). Previously published estimates of BV for bone metabolism biomarkers are generally not compliant with the most up-to-date quality criteria for BV studies. We calculated the BV and RCV for different bone metabolism markers, namely β-isomerized C-terminal telopeptide of type I collagen (β-CTX), N-terminal propeptide of type I collagen (PINP), osteocalcin (OC), intact fibroblast growth factor 23 (iFGF-23), and uncarboxylated-unphosphorylated Matrix-Gla Protein (uCuP-MGP) using samples from the European Biological Variation Study (EuBIVAS). In the EuBIVAS, 91 subjects were recruited from six European laboratories. Fasting blood samples were obtained weekly for ten consecutive weeks. The samples were run in duplicate on IDS iSYS or DiaSorin Liaison instruments. The results were subjected to outlier and variance homogeneity analysis before CV-ANOVA was used to obtain the BV estimates. We found no effect of gender upon the CVI estimates. The following CVI estimates with 95% confidence intervals (95% CI) were obtained: β-CTX 15.1% (14.4-16.0%), PINP 8.8% (8.4-9.3%), OC 8.9% (8.5-9.4%), iFGF23 13.9% (13.2-14.7%), and uCuP-MGP 6.9% (6.1-7.3%). The EuBIVAS has provided updated BV estimates for bone markers, including iFGF23, which have not been previously published, facilitating the improved follow-up of patients being treated for metabolic bone disease.

Analytical Performance Specifications for Lipoprotein(a), Apolipoprotein B-100, and Apolipoprotein A-I Using the Biological Variation Model in the EuBIVAS Population.

With increased interest in lipoprotein(a) (Lp[a]) concentration as a target for risk reduction and growing clinical evidence of its impact on cardiovascular disease (CVD) risk, rigorous analytical performance specifications (APS) and accuracy targets for Lp(a) are required. We investigated the biological variation (BV) of Lp(a), and 2 other major biomarkers of CVD, apolipoprotein A-I (apoA-I) and apolipoprotein B-100 (apoB), in the European Biological Variation Study population. Serum samples were drawn from 91 healthy individuals for 10 consecutive weeks at 6 European laboratories and analyzed in duplicate on a Roche Cobas 8000 c702. Outlier, homogeneity, and trend analysis were performed, followed by CV-ANOVA to determine BV estimates and their 95% CIs. These estimates were used to calculate APS and reference change values. For Lp(a), BV estimates were determined on normalized concentration quintiles. Within-subject BV estimates were significantly different between sexes for Lp(a) and between women aged <50 and >50 years for apoA-I and apoB. Lp(a) APS was constant across concentration quintiles and, overall, lower than APS based on currently published data, whereas results were similar for apoA-I and apoB. Using a fully Biological Variation Data Critical Appraisal Checklist (BIVAC)-compliant protocol, our study data confirm BV estimates of Lp(a) listed in the European Federation of Clinical Chemistry and Laboratory Medicine database and reinforce concerns expressed in recent articles regarding the suitability of older APS recommendations for Lp(a) measurements. Given the heterogeneity of Lp(a), more BIVAC-compliant studies on large numbers of individuals of different ethnic groups would be desirable.

Biological variation of arginine vasopressin.

There is growing interest in the measurement of plasma levels of arginine vasopressin (AVP) for the assessment of mild dehydration. However, the principles of biological variation have not been applied to the study of AVP and understanding biological variation of AVP may provide insights regarding measurement thresholds. The purpose of this investigation was to determine the biological variation of AVP in healthy euhydrated individuals to understand the potential for establishing both static and/or change thresholds of importance. We studied 29 healthy volunteers (24 men and 5 women) while controlling for hydration and pre-analytical factors. All subjects completed between 2-8 trials where biological variation was determined using widely published methods. We determined the intraindividual, interindividual, and analytical coefficients of variation (CVI, CVG, and CVA, respectively) and subsequently the index of individuality and heterogeneity (II and IH, respectively). AVP did not reach the IH threshold required to be considered useful in the dynamic assessment of physiological deviations from normal. AVP levels approached the II threshold required to be considered useful in the static assessment of physiological deviations from normal. This analysis demonstrates that AVP assessment is unlikely to yield useful information about hydration status.

A Bayesian Approach to Biological Variation Analysis.

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. The aims of this study were to develop Bayesian models to calculate BV that (a) are robust to "noisy data," (b) allow heterogeneity in the within-participant CVs, and (c) take advantage of prior knowledge. We explored Bayesian models with different degrees of robustness using adaptive Student t distributions instead of the normal distributions and when the possibility of heterogeneity of the within-participant CV was allowed. Results were compared to more standard approaches using chloride and triglyceride data from the European Biological Variation Study. Using the most robust Bayesian approach on a raw data set gave results comparable to a standard approach with outlier assessments and removal. The posterior distribution of the fitted model gives access to credible intervals for all parameters that can be used to assess reliability. Reliable and relevant priors proved valuable for prediction. The recommended Bayesian approach gives a clear picture of the degree of heterogeneity, and the ability to crudely estimate personal within-participant CVs can be used to explore relevant subgroups. Because BV experiments are expensive and time-consuming, prior knowledge and estimates should be considered of high value and applied accordingly. By including reliable prior knowledge, precise estimates are possible even with small data sets.

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

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 α1-acid glycoprotein, α1-antitrypsin, albumin, β2-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). 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. Outlier and variance homogeneity analyses were performed followed by CV-ANOVA on trend-corrected data if relevant, to determine BV and analytical variation estimates with CI and the associated RCV. For the acute phase proteins, several participants experienced mild inflammatory episodes during the study, requiring exclusion of 7% of the 25290 results. Within-subject BV (CVI) estimates for specific proteins obtained in our study were lower than those available in the online 2014 BV database, except for Trf, whereas between-subject BV (CVG) estimates were similar. CVI and CVG estimates for sTfR, which have not previously been published, were 6.0% and 19.1%, respectively. In addition to new BV estimates for sTfR, this EuBIVAS substudy generated more demanding APS for frequently requested plasma specific proteins. APS for CRP should not be calculated from BV data except when CRP is used as a risk factor for cardiovascular disease.

Effects of different anticoagulants on glycated albumin quantification.

IntroductionIn the last 20 years glycated albumin (GA) measurement has been demonstrated to be a reliable glycation marker and recently as the most innovative one in western countries. Glycated albumin has been already adopted by some Asian countries due to its usefulness in diabetes screening. The aim of the present study was to investigate for the first time the effects of different anticoagulants on GA assay.Materials and methodsFrom each of 60 patients a serum tube and K3EDTA, Li-Heparin and NaF-EDTA containing tubes were collected. All tubes were from Sarstedt (Verona, Italy). Glycated albumin was measured in duplicate in each sample tube in a single analytical run with quantILab glycated albumin (Instrumentation Laboratory SpA - A Werfen Company, Milan, Italy) on Architect c8000 analyser (Abbott SRL, Rome, Italy). Comparison of GA% in evaluated tubes was made by paired Wilcoxon test.ResultsMedian and interquartile range GA% concentrations were 15.4% (13.2 - 19.1) in serum, 15.7% (13.6 - 19.9) in K3EDTA, 15.6% (13.3 - 19.7) in Li-heparin and 15.5% (13.1 - 19.3) in NaF-EDTA samples, respectively. Glycated albumin mean relative bias respect to serum was within desirable bias derived from biological variation studies (± 2.9%) when K3EDTA (+ 2.8%), Li-heparin (+ 0.9%) or NaF-EDTA (+ 0.1%), were used as anticoagulants.ConclusionsOur results demonstrate that the GA% assay is not affected by relevant interferences when K3EDTA, Li-heparin or NaF-EDTA are used as anticoagulants, so they can be used interchangeably without a relevant impact on the clinical use of the test.

\u2018Extreme\u2019 organisms and the problem of generalization: interpreting the Krogh principle

Many biologists appeal to the so-called Krogh principle when justifying their choice of experimental organisms. The principle states that “for a large number of problems there will be some animal of choice, or a few such animals, on which it can be most conveniently studied”. Despite its popularity, the principle is often critiqued for implying unwarranted generalizations from optimal models. We argue that the Krogh principle should be interpreted in relation to the historical and scientific contexts in which it has been developed and used. We interpret the Krogh Principle as a heuristic, i.e., as a recommendation to approach biological problems through organisms where a specific trait or physiological mechanism is expected to be most distinctively displayed or most experimentally accessible. We designate these organisms “Krogh organisms”. We clarify the differences between uses of model organisms and non-standard Krogh organisms. Among these is the use of Krogh organisms as “negative models” in biomedical research, where organisms are chosen for their dissimilarity to human physiology. Importantly, the representational scope of Krogh organisms and the generalizability of their characteristics are not fixed or assumed but explored through experimental studies. Research on Krogh organisms is steeped in the comparative method characteristic of zoology and comparative physiology, in which studies of biological variation produce insights into general physiological constraints. Accordingly, we conclude that the Krogh principle exemplifies the advantages of studying biological variation as a strategy to produce generalizable insights.

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

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. Samples were drawn from 91 healthy individuals (38 male, 53 female; age range, 21-69 years) for 10 consecutive weeks at 6 European laboratories. Samples were stored at -80 °C before duplicate analysis of all samples on an ADVIA 2400 (Siemens Healthineers). Outlier and homogeneity analyses were performed, followed by CV-ANOVA on trend-corrected data, when relevant, to determine BV estimates with CIs. The within-subject BV (CVI) estimates of all measurands, except for urea and LDL cholesterol, were lower than estimates available in an online BV database, with differences being most pronounced for HDL cholesterol, glucose, and direct bilirubin. Significant differences in CVI for men and women/women <50 years of age were evident for uric acid, triglycerides, and urea. The CVA obtained for sodium and magnesium exceeded the EuBIVAS-based APS for imprecision. The EuBIVAS, which is fully compliant with the recently published Biological Variation Data Critical Appraisal Checklist, has produced well-characterized, high-quality BV estimates utilizing a stringent experimental protocol. These new reference data deliver revised and more exacting APS and reference change values for commonly used clinically important measurands, thus having direct relevance to diagnostics manufacturers, service providers, clinical users, and ultimately patients.

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

BackgroundProstate-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. MethodEuBIVAS samples were collected weekly from thirty-seven healthy males (22–59 years) for 10 weeks. All samples, stored at −80 °C, were measured in duplicate with a Roche Cobas e801. Outlier and homogeneity analysis were performed followed by CV-ANOVA to determine BV, analytical variation, analytical performance specifications (APS), reference change values (RCV) and the number of samples required to estimate the homeostatic set points. ResultsWithin-subject BV estimates were for tPSA 6.8% (6.1–7.4); fPSA 7.1% (6.5–7.7) cPSA: 8.8% (8.0–9.7) and %fPSA 5.3% (4.8–5.8), delivering RCV for increase of 15–20% and indicating that one sample is sufficient to estimate the homeostatic set points within ±15%. BV estimates for tPSA were lower than previously published estimates. Estimates for fPSA, cPSA and %fPSA have not previously been reported in healthy subjects. ConclusionsHighly powered EuBIVAS BV estimates of tPSA, fPSA, cPSA and %fPSA provide updated APS and RCV for monitoring for prostate cancer.

An overview of EFLM harmonization activities in Europe.

Abstract The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has initiated many harmonization activities in all phases of the examination process. The EFLM is dealing with both the scientific and the educational aspects of harmonization, with the intention of disseminating best practice in laboratory medicine throughout Europe. Priorities have been given (1) to establish a standard for conducting and assessing biological variation studies and to construct an evidence based EFLM webpage on biological variation data, (2) to harmonize preanalytical procedures by producing European guidelines, (3) to improve test ordering and interpretation, (4) to produce other common European guidelines for laboratory medicine and play an active part in development of clinical guidelines, (5) to establish a common basis for communicating laboratory results to patients, (6) to harmonize units of measurement throughout Europe, (7) to harmonize preanalytical procedures in molecular diagnostics and (8) to harmonize and optimize test evaluation procedures. The EFLM is also now launching the 5th version of the European Syllabus to help the education of European Specialists in Laboratory Medicine (EuSpLM), which is being supported by the development of e-learning courses. A register of EuSpLM is already established for members of National Societies in EU countries, and a similar register will be established for specialists in non-EU countries.

Storage stability of commonly used haematological parameters at 33 °C: Electronic supplementary material available online for this article.

IntroductionThis study aimed to investigate the analytical bias in haematological parameters induced by storage at 33 ºC.Materials and methodsBlood from the diversion pouch of 20 blood donors were collected in K2EDTA vials and stored at 33 ºC. Readings from each vial were taken at 0, 4, 6, 12, 24, 48 and 72 hours after collection on the Sysmex XP-100 analyser (Sysmex Corporation, Kobe, Japan). The percent difference from the baseline readings were calculated and subjected to a Wilcoxon signed rank test at a Holm corrected significance level of 0.05. A median percent difference, which was statistically significant and greater than the maximum acceptable bias (taken from studies of biological variation), was taken as evidence of unacceptable shift. If the median shift was lesser than the maximum acceptable bias, two one-sided Wilcoxon signed rank tests for equivalence were used to determine whether the percent differences were significantly lesser than the maximum acceptable bias.ResultsHaemoglobin, red blood cell count, white blood cell count, mean corpuscular haemoglobin and lymphocyte count showed acceptable bias after storage for at least 24 hours at 33 ºC. Haematocrit, mean corpuscular volume, mean corpuscular haemoglobin concentration, platelet count and mean platelet volume showed unacceptable shift in less than 4 hours when stored at 33 ºC.ConclusionsSince many haematological parameters show unacceptable bias within 4 hours of sample storage at 33 ºC, the recommended limit of time from collection to processing should be revised for areas where high environmental temperatures are common.

Harmonization initiatives in the generation, reporting and application of biological variation data.

Abstract Biological variation (BV) data have many applications in laboratory medicine. However, concern has been raised that some BV estimates in use today may be irrelevant or of unacceptable quality. A number of initiatives have been launched by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) and other parties to deliver a more harmonized practice in the generation, reporting and application of BV data. Resulting from a necessary focus upon the veracity of historical BV studies, critical appraisal and meta-analysis of published BV studies is possible through application of the Biological Variation Data Critical Appraisal Checklist (BIVAC), published in 2017. The BIVAC compliant large-scale European Biological Variation Study delivers updated high-quality BV data for a wide range of measurands. Other significant developments include the publication of a Medical Subject Heading term for BV and recommendations for common terminology for reporting of BV data. In the near future, global BV estimates derived from meta-analysis of BIVAC appraised publications will be accessible in a Biological Variation Database at the EFLM website. The availability of these high-quality data, which have many applications that impact on the quality and interpretation of clinical laboratory results, will afford improved patient care.

The Generation and Applications of Biological Variation Data in Laboratory Medicine

<h3>ABSTRACT</h3> In recent years, increasing consideration has been given to the study of biological variation on laboratory analytes. Data on biological variation have a number of applications in the laboratory, including setting the quality specifications for analytical performance, assessing the usefulness of population-based reference ranges, assessing variation in serial results from an individual, and determining the optimal sample for analyzing a specific constituent. Thus, it is essential to generate accurate and reliable data on biological variation using a standardized study protocol. Currently, there are guidelines available to enable the standardized production of biological variation data. Here, we aim to provide recommendations on preferred experimental procedures and statistical methods for producing correct biological variation data in accordance with published guidelines.