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).
In the BIVAC, publications were rated as A, B, C, or D, indicating descending compliance for 14 BIVAC quality items, focusing on study design, methodology, and statistical handling. A D grade indicated that associated BV estimates should not be applied in clinical practice. Systematic searches were applied to identify BV studies for 28 different measurands.
In total, 128 publications were identified, providing 935 different BV estimates. Nine percent achieved D scores. Outlier analysis and variance homogeneity testing were scored as C in >60% of 847 cases. Metaanalysis delivered a CV
estimate for ALT of 15.4%.
Application of BIVAC to BV publications identified deficiencies in required study detail and delivery, especially for statistical analysis. Those deficiencies impact the veracity of BV estimates. BV data from BIVAC-compliant studies can be combined to deliver robust global estimates for safe clinical application.
Rationale for using data on biological variation Ricós, Carmen; Álvarez, Virtudes; Perich, Carmen ...
Clinical chemistry and laboratory medicine,
05/2015, Letnik:
53, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The aims of this study are: 1) to use the data included in the biological variation (BV) database to address the usability of BV estimates; and 2) to use different examples from the authors’ ...laboratories to illustrate the use and the usefulness of BV data in laboratory medicine. The BV database is an essential tool for laboratory management. Examples of application of data derived from BV are given in this paper, such as analytical performance specifications that have been included in various quality control software designed to optimize operative rules; also they have been incorporated as acceptability limits in external quality assurance reports. BV data from pathological status are of utmost interest for monitoring patients and differences between the intra-individual coefficients of variation (CV
) estimated from healthy and patients are shown. However, for a number of analytes there are limited data available and for many there are no data, consequently new studies should be encouraged at an international level. In addition, developing international criteria to evaluate publications dealing with the estimation of BV components would be of the utmost interest. We are ready and willing to collaborate with such worthy initiatives. The first EFLM strategic conference on analytical performance specifications is an excellent opportunity for debating these ideas.
Numerical data on the components of biological variation (BV) have many uses in laboratory medicine, including in the setting of analytical quality specifications, generation of reference change ...values and assessment of the utility of conventional reference values.
Generation of a series of up-to-date comprehensive database of components of BV was initiated in 1997, integrating the more relevant information found in publications concerning BV. A scoring system was designed to evaluate the robustness of the data included. The database has been updated every 2 years, made available on the Internet and derived analytical quality specifications for imprecision, bias and total allowable error included in the tabulation of data.
Our aim here is to document, in detail, the methodology we used to evaluate the reliability of the included data compiled from the published literature. To date, our approach has not been explicitly documented, although the principles have been presented at many symposia, courses and conferences.
•BV data for testosterone, FSH, prolactin, LH and DHEA-S in 38 men by CV-ANOVA is presented.•BV data of prolactin and DHEA-S in men is reported for the first time.•Low II suggests RCV is valuable for ...interpretation of an individual’s test results.•The APS for imprecision for the hormones varied between 4 and 11 %.•No hormone concentration differences between the five nationalities studied.
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.
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. We derived within-subject (CVI) and between-subject (CVG) BV estimates by CV-ANOVA after trend, outlier, and homogeneity analysis and calculated reference change values, index of individuality (II), and analytical performance specifications.
The CVI estimates were 10 % for testosterone, 8 % for FSH, 13 % for prolactin, 22 % for LH, and 9 % for DHEA-S, respectively. The IIs ranged between 0.14 for FSH to 0.66 for LH, indicating high individuality.
In this study, we have used samples from the highly powered EuBIVAS study to derive BV estimates for testosterone, FSH, prolactin, LH and DHEA-S in men. Our data confirm previously published BV estimates of testosterone, FSH and LH. For prolactin and DHEA-S BV data for men are reported for the first time.
Standardization is the ability to obtain interchangeable results leading to same medical interpretation. External quality assessment (EQA) is the main support of the on-going harmonization ...initiatives. Aim of study was to evaluate results obtained from two years category 1 EQA program experience in Spain and determine the impact of applying this type of EQA program on the analytical standardization.
According to the analytical method, traceability and instrument different groups were established which results were evaluated by calculating mean, coefficient of variation and percent of deviation to the reference value. Analytical performance specifications used to the results' evaluation were derived from biological variation for bias and from the inter-laboratory coefficients of variation found in a previous pilot study.
Only creatinine measured by enzymatic methods gave excellent results, although few laboratories used this method. Creatine kinase and GGT gave good precision and bias in all, but one instrument studied. For the remaining analytes (ALT, ALP, AST, bilirubin, calcium, chloride, glucose, magnesium, potassium, sodium, total protein and urate) some improvement is still necessary to achieve satisfactory standardization in our setting.
The two years of category 1 EQA program experience in Spain have manifested a lack of standardization of 17 most frequent biochemistry tests used in our laboratories. The impact of the information obtained on the lack of standardization is to recommend abandoning methods such as ALT, AST without exogenous pyridoxal phosphate, Jaffe method for creatinine, and do not use non-commutable calibrators, such as aqueous solutions for calcium and sodium.
Abstract 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). Methods Ninety EuBIVAS non-diabetic subjects (52F, 38M) from five countries had fasting HOMA-IR and QUICKI calculated from plasma glucose and insulin samples collected concurrently on 10 weekly occasions. The within-subject (CV I ) and between-subject (CV G ) BV estimates with 95 % CIs were obtained by CV-ANOVA after analysis of trends, variance homogeneity and outlier removal. Results The CV I of HOMA-IR was 26.7 % (95 % CI 25.5–28.3), driven largely by variability in plasma insulin and the CV I for QUICKI was 4.1 % (95 % CI 3.9–4.3), reflecting this formula’s logarithmic transformation of glucose and insulin values. No differences in values or BV components were observed between subgroups of men or women below and above 50 years. Conclusions The EuBIVAS, by utilising a rigorous experimental protocol, has produced robust BV estimates for two of the most commonly used markers of insulin resistance in non-diabetic subjects. This has shown that HOMA-IR, in particular, is highly variable in the same individual which limits the value of single measurements.
Stability of a measurand in a specimen is a function of the property variation over time in specific storage conditions, which can be expressed as a stability equation, and is usually simplified to ...stability limits (SLs). Stability studies show differences or even inconsistent results due to the lack of standardized experimental designs and heterogeneity of the chosen specifications. Although guidelines for the validation of sample collection tubes have been published recently, the measurand stability evaluation is not addressed. This document provides an easy guideline for the development of a stability test protocol based on a two-step process. A preliminary test is proposed to evaluate the stability under laboratory habitual conditions. The loss of stability is assessed by comparing measurement values of two samples obtained from the same patient and analyzed at different time points. One of them is analyzed under optimal conditions (basal sample). The other is stored under specific stability conditions for a time set by the laboratory (test sample). Differences are expressed using percentage deviation (PD%) to facilitate comparison with specifications. When the preliminary test demonstrates instability, a comprehensive test is proposed in order to define the stability equation and to specify SLs. Several samples are collected from a set of patients. The basal sample is analyzed under optimal conditions, whereas analysis of test samples is delayed at time intervals. For each patient PD% is calculated as the difference between measurements for every test sample and its basal one and represented in a coordinate graph versus time.
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.
The project involved six European laboratories (Milan, Italy; Bergen, Norway; Madrid, Spain; Padua, Italy; Istanbul, Turkey; Assen, The Netherlands). Blood samples were collected from 97 volunteers (44 men, aged 20-60 years; 43 women, aged 20-50 years; 10 women, aged 55-69 years). Initial subject inclusion required that participants completed an enrolment questionnaire to verify their health status. The volunteers provided blood specimens once per week for 10 weeks. A short questionnaire was completed and some laboratory tests were performed at each sampling consisting of blood collected under controlled conditions to provide serum, K2EDTA-plasma and citrated-plasma samples.
Samples from six out of the 97 enroled subjects were discarded as a consequence of abnormal laboratory measurements. A biobank of 18,000 aliquots was established consisting of 120 aliquots of serum, 40 of EDTA-plasma, and 40 of citrated-plasma from each subject. The samples were stored at -80 °C.
A biobank of well-characterised samples collected under controlled conditions has been established delivering a European resource to enable production of contemporary BV data.
Abstract
Objectives
The estimates of biological variation (BV) have traditionally been determined using direct methods, which present limitations. In response to this issue, two papers have been ...published addressing these limitations by employing indirect methods. Here, we present a new procedure, based on indirect methods that analyses data collected within a multicenter pilot study. Using this method, we obtain CV
I
estimates and calculate confidence intervals (CI), using the EFLM-BVD CV
I
estimates as gold standard for comparison.
Methods
Data were collected over a 18-month period for 7 measurands, from 3 Spanish hospitals; inclusion criteria: patients 18–75 years with more than two determinations. For each measurand, four different strategies were carried out based on the coefficient of variation ratio (rCoeV) and based on the use of the bootstrap method (OS1, RS2 and RS3). RS2 and RS3 use symmetry reference change value (RCV) to clean database.
Results
RS2 and RS3 had the best correlation for the CV
I
estimates with respect to EFLM-BVD. RS2 used the symmetric RCV value without eliminating outliers, while RS3 combined RCV and outliers. When using the rCoeV and OS1 strategies, an overestimation of the CV
I
value was obtained.
Conclusions
Our study presents a new strategy for obtaining robust CV
I
estimates using an indirect method together with the value of symmetric RCV to select the target population. The CV
I
estimates obtained show a good correlation with those published in the EFLM-BVD database. Furthermore, our strategy can resolve some of the limitations encountered when using direct methods such as calculating confidence intervals.
The Commission of Analytical Quality and the Committee of External Quality Programs of Spanish Society of Laboratory Medicine (SEQC) in collaboration with the Dutch Foundation for the Quality ...organized the first national category 1 External Quality Assessment Programs (EQAP) pilot study. The aim is to evaluate the standardization of serum creatinine measurements in the Spanish laboratories through a category 1 external quality assurance program with commutable material and reference method assigned values.
A total of 87 Spanish laboratories were involved in this program in 2015. Each day a sample control was measured by duplicate during 6 consecutive days. Percentage deviations and coefficients of variation obtained were compared with quality specifications derived from biological variation.
A total of 1044 creatinine results were obtained. Laboratories were coded in 11 different method-traceability combinations. Only enzymatic methods get all results within the acceptability limits.
To participate in a category 1 EQAP is a valuable tool to assess the standardization degree in our country; a big effort should be made to promote laboratories to change their procedures and to use enzymatic creatinine methods, in order to achieve a satisfactory standardization degree for this important analyte.
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