Biological variation: Evaluation of methods for constructing confidence intervals for estimates of within-person biological variation for different distributions of the within-person effect.

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 .

METHOD: 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 CVI and 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.

CONCLUSION: 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.