Production of reference values is cumbersome and only few laboratories actually produce reference values by themselves. Most clinical laboratories depend on reference limits produced in other laboratories.

It is customary that the validity of the "borrowed" reference intervals is checked by analyzing a small number of samples from healthy individuals. There is an apparent need for a powerful statistical method to extract as much information as possible from these samples.

With increased capacity of computers computing intensive statistical methods have become a practical choice for treatment and estimation of data. Holmes et al. (Clin Chem 1994;40:2216-2222) presented a method based on Monte Carlo simulation sampling technique for the verification of reference intervals. We developed software, Refstat for Windows, which applies the method suggested by them.

Refstat for Windows is a practical tool for the evaluation of the validity of reference values. Even if only few control samples and results are available, the validity of the reference distribution can still be evaluated. However, we recommend that at least about 20 control specimens are used. The minimum number of control results accepted by the program is 7.

Refstat uses a computer intensive Monte Carlo simulation resampling technique, which is essentially a non-parametric method without any distributional assumptions. All parts of the reference distribution, including the reference limits themselves, are checked and corresponding p-values calculated for comprehensive evaluation of the validity of reference values.

Probably the greatest practical problem in the application of the method is that laboratories which produce original reference values still often report only the reference limits and not the whole set of reference values. We suggest that this problem could be solved by the international generation of reference values "banks" that could be accessed via the World Wide Web.

Refstat will be available in September 1997 for downloading through the GraphROC for Windows WWW-site: