Determining reference ('normal') limits in medicine: an application

We provide an account of a study to assess reference limits for eight routine laboratory determinations at the Academic Hospital of the Free University, Amsterdam and emphasize methodological issues rather than results. We argue that reference limits have use mainly in the first phase of the diagnostic process. Reference and target populations should be grossly comparable, and therefore patients (after slight selection) could well serve as references. However, we found major differences between in- and out-patients, so we suggest that this factor, together with age and sex, be taken into account. To arrive at reliable limits, the size of the reference sample should be at least 100. Laboratory reports should provide percentiles, which enable a more flexible decision than do fixed limits.