title: Analytical performance specifications for changes in assay bias (Δbias) for data with logarithmic distributions as assessed by effects on reference change values.
abstract: Background The distributions of within-subject biological variation are usually described as coefficients of variation, as are analytical performance specifications for bias, imprecision and other characteristics. Estimation of specifications required for reference change values is traditionally done using relationship between the batch-related changes during routine performance, described as Δbias, and the coefficients of variation for analytical imprecision (CVA): the original theory is based on standard deviations or coefficients of variation calculated as if distributions were Gaussian. Methods The distribution of between-subject biological variation can generally be described as log-Gaussian. Moreover, recent analyses of within-subject biological variation suggest that many measurands have log-Gaussian distributions. In consequence, we generated a model for the estimation of analytical performance specifications for reference change value, with combination of Δbias and CVAbased on log-Gaussian distributions of CVIas natural logarithms. The model was tested using plasma prolactin and glucose as examples. Results Analytical performance specifications for reference change value generated using the new model based on log-Gaussian distributions were practically identical with the traditional model based on Gaussian distributions. Conclusion The traditional and simple to apply model used to generate analytical performance specifications for reference change value, based on the use of coefficients of variation and assuming Gaussian distributions for both CVIand CVA, is generally useful.
authors.affiliation: 1 Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Hillerød, Denmark.|2 Norwegian Quality Improvement of Primary Care Laboratories (NOKLUS), Section for General Practice, University of Bergen, Bergen, Norway.
authors.forename: Per H
authors.initials: PH
authors.lastname: Petersen
authors.affiliation: 1 Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Hillerød, Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Lund
authors.affiliation: 3 Centre for Research into Cancer Prevention and Screening, University of Dundee, Dundee, Scotland.
authors.forename: Callum G
authors.initials: CG
authors.lastname: Fraser
authors.affiliation: 1 Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Hillerød, Denmark.
authors.forename: György
authors.initials: G
authors.lastname: Sölétormos
mesh_terms: D015982:Bias; D001681:Biological Assay / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D005189:False Positive Reactions; D006801:Humans; D012016:Reference Values; D016008:Statistical Distributions
keywords: Analytical imprecision; analytical performance specifications; interbatch systematic variation; logarithmic distributions; reference change values; within-subject biological variation