Nonparametric Estimation of Reference Intervals by Simple and Bootstrap-based Procedures

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Abstract
In recent years, increasing interest has arisen in nonparametric estimation of reference intervals. The IFCC recommendation focuses on the nonparametric procedure, and the NCCLS guideline on reference interval estimation deals exclusively with the nonparametric approach ( 1)( 2). The mentioned reports are based on the simple nonparametric approach, taking as a basis the sorted sample values. In addition to this basic approach, modern computer-based procedures have been introduced, which have made it possible to attain slightly increased precision for the nonparametric approach by applying resampling methods, weighted percentile estimation, or smoothing techniques ( 3)( 4). In the present report, both the simple nonparametric reference interval estimation procedure and the resampling (bootstrap) principle were studied using simulations based on distribution types that should be relevant for clinical chemistry, i.e., gaussian and skewed distributions.