A new approach to sample size calculation for reference interval studies

Abstract A new criterion is proposed for determining the sample size required for a study performed for the purpose of establishing reference intervals. The basic idea behind the criterion is to compare the empirical coverage (i.e. the probability content) of the reference region obtained from the sample with its target value (e.g. 95 per cent) and to set suitable limits δ 1 , δ 2 to the difference between both quantities which must not be exceeded with sufficiently large probability β (e.g. β=90 per cent). For the most frequently used parametric and distribution‐free methods of estimating univariate reference limits, implicit formulae are derived relating the sample size to the design parameters δ 1 , δ 2 and β. For symmetric specification of (δ 1 , δ 2 ), explicit approximation formulae for the computation of n are given. Exact values obtained by means of suitable numerical techniques are presented in a set of tables covering specifications of δ 1 , δ 2 and β which can be recommended for real applications. The tables can be used both for one‐ and two‐sided reference intervals. Copyright © 2005 John Wiley & Sons, Ltd.