Received on June 26, 2003
Accepted on February 25, 2004

General Clinical Chemistry

Centile Charts I: New Method of Assessment for Univariate Reference Intervals

¹ School of Mathematics, Cardiff University, Senghennydd Road, PO Box 926, Cardiff CF24 4YH, United Kingdom
² Department of Epidemiology Statistics and Public Health, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom

^* To whom correspondence should be addressed. E-mail: iles{at}cardiff.ac.uk.

Background: We introduce a new criterion, the percentile inclusion probability, for comparing methods for calculating reference intervals. The criterion is compared with a previously published measure of reliability suggested by Linnet (Linnet K. Clin Chem 1987;33:381-6), the ratio of the width of the confidence interval for the percentile to that of the reference interval.

Methods: Data are simulated from a range of theoretical statistical distributions representing the shapes of data sets encountered in clinical investigations. The two-stage transformation of the data to a gaussian distribution recommended by the IFCC is compared with a nonparametric approach.

Results: The percentile inclusion probability criterion identifies that the parametric approach is in some cases seriously affected by bias. Using different parametric models, we compare nonparametric and parametric methods for two sets of clinical data and show that the parametric approach is susceptible to model choice.

Conclusions: Sample sizes significantly greater than those currently recommended are required to establish reference intervals, regardless of whether parametric or nonparametric methods are used. Parametric methods are preferable when the data are truly gaussian, but are only marginally better than nonparametric methods when data transformation is needed to achieve a gaussian shape.