Estimating reference intervals.

As indicated in the thought-provoking article in this issue of the Journal by Katayev and colleagues,1 there are few things more important than the reference intervals we report along with our laboratory measurements. Unfortunately, we laboratory professionals give them far too little attention, adopting manufacturers’ recommended intervals, often without even verifying them ourselves and, rarely, if ever, establishing our own values. Thus, the article “Establishing Reference Intervals for Clinical Laboratory Test Results: Is There a Better Way?” is certain to attract much attention. Katayev and colleagues1 make several assertions that bear comment. They claim that there is no clear guideline as to which technique to use, but the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine2 and the CLSI3 are quite clear. If one collects samples carefully from 120 vetted healthy people, then the technique of choice is nonparametric analysis. The reason for this is that the nonparametric technique requires no knowledge of, and makes no assumptions about, the nature of the data distribution. In other words, the reference interval values obtained are valid no matter what the underlying distribution is. If one has fewer samples, again from carefully screened, apparently healthy people, one can use a parametric technique with as few as 40 points, so long as the original data (or some transformed version of the data) exhibit a gaussian distribution. And with even fewer than 40 data points, one can use robust techniques to get an estimate of the reference interval.3,4 Notwithstanding the assertions by Katayev and colleagues,1 the reference intervals obtained from properly collected and analyzed data do not vary depending on the technique used.3 Katayev and colleagues1 also make the point that it becomes prohibitively difficult to collect sufficient data for all the …