Within-subject biological variation in disease: collated data and clinical consequences

Ricós, Carmen; Iglesias, Natàlia; García-Lario, José-Vicente; Simón, Margarita; Cava, Fernando; Hernández, Amparo; Perich, Carmen; Minchinela, Joana; Álvarez, Virtudes; Doménech, Maria-Vicenta; Jiménez, Carlos-Víctor; Biosca, Carmen; Tena, Raquel

doi:10.1258/000456307780945633

Cited by 169 publications

(126 citation statements)

References 32 publications

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“…Normal biological variability comprises within‐subject (intraindividual) and among‐subject (interindividual) variation, both of which might be similar or different between health and various disease states 18, 24…”

Section: Biomarker Characteristicsmentioning

confidence: 99%

“…Sources of biological variation include rhythmic expression or secretion, variation in gastrointestinal passage or patchy distribution of cells expressing and releasing a biomarker measured in feces, and the metabolism and half‐life of a biomarker (determined by its size, charge, hydrophobicity, and route of excretion) 18, 24. Such sources of biological variation must be recognized and strategies developed to counterbalance such variation (eg, by collecting specimens on multiple days or at a certain time of the day).…”

Section: Biomarker Characteristicsmentioning

confidence: 99%

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Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Heilmann

Steiner

2018

Veterinary Internal Medicne

108

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Chronic inflammatory enteropathies (CIE) in dogs are a group of disorders that are characterized by chronic persistent or recurrent signs of gastrointestinal disease and histologic evidence of mucosal inflammation. These CIEs are classified as either food‐responsive, antibiotic‐responsive, or immunosuppressant‐responsive enteropathy. Patients not clinically responding to immunomodulatory treatment are grouped as nonresponsive enteropathy and dogs with intestinal protein loss as protein‐losing enteropathy. Disease‐independent clinical scoring systems were established in dogs for assessment of clinical disease severity and patient monitoring during treatment. Histopathologic and routine clinicopathologic findings are usually not able to distinguish the subgroups of CIE. Treatment trials are often lengthy and further diagnostic tests are usually at least minimally invasive. Biomarkers that can aid in defining the presence of disease, site of origin, severity of the disease process, response to treatment, or a combination of these would be clinically useful in dogs with CIE. This article summarizes the following biomarkers that have been evaluated in dogs with CIE during the last decade, and critically evaluates their potential clinical utility in dogs with CIE: functional biomarkers (cobalamin, methylmalonic acid, folate, α1‐proteinase inhibitor, immunoglobulin A), biochemical biomarkers (C‐reactive protein, perinuclear anti‐neutrophilic cytoplasmic antibodies, 3‐bromotyrosine, N‐methylhistamine, calprotectin, S100A12, soluble receptor of advanced glycation end products, cytokines and chemokines, alkaline phosphatase), microbiomic biomarkers (microbiome changes, dysbiosis index), metabolomic biomarkers (serum metabolome), genetic biomarkers (genomic markers, gene expression changes), and cellular biomarkers (regulatory T cells). In addition, important performance criteria of diagnostic tests are briefly reviewed.

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Section: Biomarker Characteristicsmentioning

confidence: 99%

Section: Biomarker Characteristicsmentioning

confidence: 99%

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Heilmann

Steiner

2018

Veterinary Internal Medicne

108

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“…In consequence, the real RCV in these patients would be higher than in the healthy. However, a compilation of known data on CV I in diseases [24] and comparison with relevant data in the healthy suggests that, in general, CV I are indeed similar in health and chronic stable disease. In conclusion, for most quantities, data on health can be used appropriately in monitoring of disease [25].…”

Section: Limits Of the Studymentioning

confidence: 99%

Advantages of the lognormal approach to determining reference change values for N-terminal propeptide B-type natriuretic peptide

Klersy

d’Eril

Barassi

et al. 2012

Clinica Chimica Acta

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Background: Serial measurement of NT-proBNP is performed routinely in the monitoring and assessment of the effectiveness of therapy in patients being treated for chronic heart failure (CHF). Intra-individual changes in NT-proBNP levels over time are compared typically to a reference change value (RCV) determined using either a standard [i.e., nested analysis of variance (nANOVA)] or a lognormal approach. The RCV defines the minimum percent change in serial analyte values that exceeds the percent change expected due to biological variation alone. Currently, there is no consensus on which approach (nANOVA or lognormal) to determining RCV is better. Aims: Based on these considerations, we aimed to illustrate the impact of data transformation on the calculation of the biological variation of NT-proBNP and discuss the utility of logarithmic transformation in monitoring patients with heart failure. Methods: 15 healthy subjects were enrolled after informed consent; 5 blood specimens were collected twice a week. Nested ANOVA from replicate analyses was applied to obtain components of biological variation, on the raw data and after data transformation. Results: NT-proBNP distribution being highly skewed required data transformation. Natural log transformation yielded normalization. An example demonstrates that for untransformed values the RCV was overestimated for low concentrations of NT-proBNP and underestimated for higher concentrations. Conclusions: Log-transformed data are often used in the establishment of reference intervals for evaluating laboratory tests results in clinical practice, especially when the reference interval data are not Gaussian distributed. As log-normal approach is the best approach to determining RCV values we encourage its use assessing the clinical utility of NT-proBNP serial testing. We propose that the log-normal approach becomes the standard approach to determining RCV and replaces the use of nANOVA.

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“…Between-subjects or inter-individual biological variation is defined as the difference between the set-points of individuals (13,14). Quantitative data of the components of biological variation have been used to assess the utility of population-based reference intervals through the index of individuality (II) (15,16), and to calculate the reference change value (RCV) required for the assessment of the significance of changes in serial results from an individual (17,18). Likewise, it has been suggested that desirable analytical quality specifications are best based on components of biological variation (19,20).…”

Section: Introductionmentioning

confidence: 99%

Biological variation of free plasma amino acids in healthy individuals

Corte

Venta²

2009

Clinical Chemistry and Laboratory Medicine

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Background: Biological variation data for free plasma amino acids are lacking from the more comprehensive databases. Therefore, we determined the intra-and inter-individual components of variation in healthy subjects. These data were used to define desirable goals for imprecision, bias and total error, indices of individuality and reference change values. Methods: Plasma samples were collected from 11 volunteers at weekly intervals over 5 weeks. Free plasma amino acids were analyzed by reversed-phase HPLC and analytical and biological variation data were derived using ANOVA. Results: Intra-individual coefficients of variation ranged from 9.5% to 46.4%, with lower values among the essential amino acids. The mean inter-individual coefficient of variation was 46.6% and was higher than intra-individual values for all amino acids. Thus, indices of individuality were below 0.8. Reference change values ranged from 30.9% to 128.4% and total error values ranged from 15.2% to 61.0%. Conclusions: Plasma amino acids exhibit relatively low intra-individual coefficients of variation, with essential amino acids showing tighter homeostatic control. Analytical quality goals can be reasonably achieved with current methods. Reference intervals are of limited value in the detection of unusual results in an individual. Therefore, comparison of serial results by means of the reference change values is recommended. Clin Chem Lab Med 2010;48:99-104.

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Within-subject biological variation in disease: collated data and clinical consequences

Cited by 169 publications

References 32 publications

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Advantages of the lognormal approach to determining reference change values for N-terminal propeptide B-type natriuretic peptide

Biological variation of free plasma amino acids in healthy individuals

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