title: Biological variation: Evaluation of methods for constructing confidence intervals for estimates of within-person biological variation for different distributions of the within-person effect.
abstract: BACKGROUND
  Precise estimates of the within-person biological variation, CVI, can be essential both for monitoring patients and for setting analytical performance specifications. The confidence interval, CI, may be used to evaluate the reliability of an estimate, as it is a good measure of the uncertainty of the estimated CVI. The aim of the present study is to evaluate and establish methods for constructing a CI with the correct coverage probability and non-cover probability when estimating CVI.
  
  
  METHODS
  Data based on 3 models for distributions for the within-person effect were simulated to assess the performance of 3 methods for constructing confidence intervals; the formula based method for the nested ANOVA, the percentile bootstrap and the bootstrap-t methods.
  
  
  RESULTS
  The performance of the evaluated methods for constructing a CI varied, both dependent on the size of the CVIand the type of distributions. The bootstrap-t CI have good and stable performance for the models evaluated, while the formula based are more distribution dependent. The percentile bootstrap performs poorly.
  
  
  CONCLUSIONS
  CI is an essential part of estimation of the within-person biological variation. Good coverage probability and non-cover probabilities for CI are achievable by using the bootstrap-t combined with CV-ANOVA. Supplemental R-code is provided online.
authors.affiliation: Norwegian Quality Improvement of Primary Care Laboratories (NOKLUS), Haraldsplass Deaconess Hospital, Bergen, Norway; Department of Global Public Health and Primary Care, University of Bergen, Norway. Electronic address: thomas.roraas@me.com.
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 (NOKLUS), Haraldsplass Deaconess Hospital, Bergen, Norway.
authors.forename: Per Hyltoft
authors.initials: PH
authors.lastname: Petersen
authors.affiliation: Norwegian Quality Improvement of Primary Care Laboratories (NOKLUS), Haraldsplass Deaconess Hospital, Bergen, Norway; Department of Global Public Health and Primary Care, University of Bergen, Norway; Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
authors.forename: Sverre
authors.initials: S
authors.lastname: Sandberg
mesh_terms: D019963:Clinical Chemistry Tests; D016001:Confidence Intervals; D006801:Humans; D015233:Models, Statistical; D012984:Software
keywords: ANOVA; Bootstrap; Confidence interval; Coverage probability; Nonparametric; Within-person biological variation