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.
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. Relevant studies were evaluated by the Biological Variation Data Critical Appraisal Checklist (BIVAC) and meta-analyses were performed for BIVAC compliant studies to deliver global estimates of within-subject (CV
) and between-subject (CV
) BV with 95% CI.
The systematic review identified 49 studies delivering results for 22 tumor markers; four papers received BIVAC grade A, 3 B, 27 C and 15 D. Out of these, 29 CV
and 29 CV
estimates met the criteria to be included in the meta-analysis. Robust data are lacking to conclude on the relationship between BV and different disease states and tumor marker concentrations.
This review identifies a lack of high-quality BV studies for many tumor markers and a need for delivery of BIVAC compliant studies, including in different disease states and tumor marker concentrations. As of yet, the state-of-the-art may still be the most appropriate model to establish analytical performance specifications for the majority of tumor markers.
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.
The Fourth Universal Definition of Myocardial Infarction Global Taskforce recommends the use of high sensitive troponin (hs-Tn) assays in the diagnosis of acute myocardial infarction. We evaluated ...the analytical performance of the Atellica IM High-sensitivity Troponin I Assay (hs-TnI) (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) and compared its performance to other hs-TnI assays (Siemens Advia Centaur, Dimension Vista, Dimension EXL, and Abbott Architect (Wiesbaden, Germany)) at one or more sites across Europe.
Precision, detection limit, linearity, method comparison, and interference studies were performed according to Clinical and Laboratory Standards Institute protocols. Values in 40 healthy individuals were compared to the manufacturer’s cut-offs. Sample turnaround time (TAT) was examined.
Imprecision repeatability CVs were 1.1–4.7% and within-lab imprecision were 1.8–7.6% (10.0–25,000 ng/L). The limit of blank (LoB), detection (LoD), and quantitation (LoQ) aligned with the manufacturer’s values of 0.5 ng/L, 1.6 ng/L, and 2.5 ng/L, respectively. Passing-Bablok regression demonstrated good correlations between Atellica IM analyser with other systems; some minor deviations were observed. All results in healthy volunteers fell below the 99th percentile URL, and greater than 50% of each sex demonstrated values above the LoD. No interference was observed for biotin (≤ 1500 µg/L), but a slight bias at 5.0 g/L haemoglobin and 50 ng/L Tn was observed. TAT from was fast (mean time = 10.9 minutes) and reproducible (6%CV).
Real-world analytical and TAT performance of the hs-TnI assay on the Atellica IM analyser make this assay fit for routine use in clinical laboratories.
Biological variation gives valuable information about how the living organism regulates its constituents within and between subjects; this information on the behavior of body components allows us to ...derive consequences concerning reference populations and intervals. With a more pragmatic approach biological variation has three uses: setting the appropriate analytical performance specification for each analyte to limit the amount of error that laboratory could introduce in its measurements, to help distinguish health from disease, and to implement internal quality control with the automatic verification of results.
INTRODUCTION
Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of ...individual‐level data.
METHODS
We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p‐tau181, p‐tau217, p‐tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10 weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within‐ (CVI) and between‐subject (CVG) BV, analytical variation, and reference change values (RCV).
RESULTS
Biomarkers presented considerable variability in CVI and CVG. Aβ42/Aβ40 had the lowest CVI (≈ 3%) and p‐tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase).
DISCUSSION
BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions.
Highlights
Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between‐ and within‐subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls.
Plasma phosphorylated tau variants significantly vary in their within‐subject biological variation, but their substantial fold‐changes in AD likely limits the impact of their variability.
Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between‐subject variation, the impact of which will depend on clinical context.
Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level.
Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result.
Biological variation (BV) has multiple applications in a variety of fields of clinical laboratory. The use of BV in statistical modeling is twofold. On the one hand, some models are used for the ...generation of BV estimates (within- and between-subject variability). Other models are built based on BV in combination with other factors to establish ranges of normality that will help the clinician interpret serial results for the same subject. There are two types of statistical models for the calculation of BV estimates: A. Direct methods, prospective studies designed to calculate BV estimates; i. Classic model: developed by Harris and Fraser, revised by the Working Group on Biological Variation of the European Federation of Laboratory Medicine. ii. Mixed-effect models. iii. Bayesian model. B. Indirect methods, retrospective studies to derive BV estimates from large databases of results. Big data. Understanding the characteristics of these models is crucial as they determine their applicability in different settings and populations. Models for defining ranges that help in the interpretation of individual serial results include: A. Reference change value and B. Bayesian data network. In summary, this review provides an overview of the models used to define BV components and others for the follow-up of patients. These models should be exploited in the future to personalize and improve the information provided by the clinical laboratory and get the best of the resources available.
Resumen
Objectivos
Un programa de control externo distribuye las mismas muestras control entre varios laboratorios y evalúa los resultados obtenidos con un criterio común. El objetivo de este trabajo ...es resumir la evolución de los programas externos, poner de manifiesto los progresos conseguidos y deducir consecuencias prácticas para el laboratorio participante.
Métodos
El material es una breve revisión de los diferentes tipos de programas externos utilizados a lo largo de cuarenta años. El método es el análisis crítico de las ventajas e inconvenientes de cada modelo, a la luz de nuestra experiencia.
Resultados
A mitad del siglo XX se iniciaron los programas EQA, detectándose gran discrepancia entre resultados emitidos por distintos laboratorios. Se desarrollaron EQA en muchos países y se propusieron mecanismos para armonizarlos, como: establecer especificaciones derivadas de la variación biológica, promover el uso de métodos analíticos homogéneos, usar el EQA como herramienta educacional. A partir del 2000 se hacen importantes avances: asegurar el adecuado uso clínico de las pruebas del laboratorio, utilizar material control conmutable con el espécimen humano, armonizar los distintos modelos de EQA, promover una organización de cooperación entre organizadores de programas EQA.
Conclusiones
Participar en un EQA con controles conmutables y valores asignados por método de referencia certificado permite conocer la inexactitud real de los resultados y el impacto en las muestras de pacientes. Si se participa en programas con controles no conmutables solo se conoce si la prestación del laboratorio es similar a la de otros usuarios del mismo método analítico.
Abstract Objectives Despite clinical guidelines do not recommend the use of point-of-care testing (POCT) glucometers for diagnostic purposes yet, the analytical performance is continuously improving. ...Thus, we evaluate the technical accuracy and clinical concordance of POCT glucometers during an oral glucose tolerance test (OGTT) in children for prediabetes and diabetes diagnosis in a comparison study. Methods Pediatric patients with an OGTT indication who attended the Diabetes Unit between December 2020 and September 2021 were recruited for this prospective observational study. During the functional test, glycaemia was immediately measured in venous blood using two glucometers (unconnected and connected) and sent to the central laboratory. Results The study included 98 patients. There was a high correlation between the glucometers and the central laboratory (Pearson correlation coefficient=0.912 and 0.950, for unconnected and connected glucometer, respectively). The median OGTT turnaround time (TAT) was significantly decreased (connected glucometer: 2.02 h interquartile range, 2.00–2.07, central laboratory: 11.63 h 6.09–25.80), with similar overall cost. The diagnostic concordance between connected glucometer and the central laboratory was 71.1 % (95 % confidence interval (CI) 61.5–79.2). The clinical decision would have been the same in the 92.8 % of the cases, but treatment would have not been indicated in 4 patients (4.1 %). Conclusions POCT glucometers have demonstrated a high correlation and an acceptable diagnostic concordance with the central laboratory during an OGTT, as well the connected device offers a significant decrease in TAT, without increasing costs. However, as severe clinical impact could happen, POCT glucometers may not be used for diagnosis yet.
The objective of the present study was to examine the evolution of the analytical performance specifications (APS) used in External Quality Assurance (EQA) schemes, as well as the efficacy of a ...category 1 EQA scheme in monitoring the harmonization of clinical laboratory results in Spain.
A review of the literature on the types of quality specifications used in schemes in other countries and their evolution was performed. In addition, a comparative analysis of the potential impact that different APS from eight countries had on clinical decision-making was made based on three measurands: sodium, thyroid-stimulating hormone (TSH), and activated partial thromboplastin time (aPTT).
Harmonization of analytical methods was demonstrated by assessing whether average results deviated from the certified reference value of control materials within the APS derived from biological variation (BV). The APS used in EQA have evolved from state-of-the-art models to BV. Poor clinical decision-making would occur if the results accepted by some APS were applied.
In Spain, only 2 of the 18 measurands studied are considered to be well harmonized. Closer collaboration between laboratories and analytical system providers would be required to resolve discrepancies.
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