title: Biological Variation: The Effect of Different Distributions on Estimated Within-Person Variation and Reference Change Values.
abstract: Good estimates of within-person biological variation, CVI, are essential for diagnosing and monitoring patients and for setting analytical performance specifications. The aim of the present study was to use computer simulations to evaluate the impact of various measurement distributions on different methods for estimating CVI and reference change value (RCV).
  
  
  
  Data were simulated on the basis of 3 models for distributions of the within-person effect. We evaluated 3 different methods for estimating CVI: standard ANOVA, ln-ANOVA, and CV-ANOVA, and 3 different methods for calculating RCV: classic, ln-RCV, and a nonparametric method. We estimated CVI and RCV with the different methods and compared the results with the true values.
  
  
  
  The performance of the methods varied, depending on both the size of the CVI and the type of distributions. The CV-ANOVA model performed well for the estimation of CVI with all simulated data. The ln-RCV method performed best if data were ln-normal distributed or CVI was less than approximately 12%. The nonparametric RCV method performed well for all simulated data but was less precise.
  
  
  
  The CV-ANOVA model is recommended for both calculation of CVI and the step-by-step approach of checking for outliers and homogeneity in replicates and samples. The standard method for calculation of RCV should not be used when using CVs.
authors.affiliation: Norwegian Quality Improvement of Primary Care Laboratories, Haraldsplass Deaconess Hospital, Bergen, Norway; Department of Global Public Health and Primary Care, University of Bergen, Norway, and thomas.roraas@noklus.no.
authors.forename: Thomas
authors.initials: T
authors.lastname: Røraas
authors.affiliation: Department of Mathematics, University of Bergen, Norway;
authors.forename: Bård
authors.initials: B
authors.lastname: Støve
authors.affiliation: Norwegian Quality Improvement of Primary Care Laboratories, Haraldsplass Deaconess Hospital, Bergen, Norway;
authors.forename: Per Hyltoft
authors.initials: PH
authors.lastname: Petersen
authors.affiliation: Norwegian Quality Improvement of Primary Care Laboratories, Haraldsplass Deaconess Hospital, Bergen, Norway; Department of Global Public Health and Primary Care, University of Bergen, Norway, and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
authors.forename: Sverre
authors.initials: S
authors.lastname: Sandberg
mesh_terms: D003198:Computer Simulation / Q000592:standards*; D006801:Humans; D012016:Reference Values