Selecting clinically relevant populations for reference intervals.

The selection of individuals to represent a group for any purpose can commit the effort to success or failure from the very outset. The description of this group must reflect what is, in reality, the purpose for which the group is being studied. Considering that reference intervals are designed to assist clinicians during diagnostic triage, criteria must reflect the nature of the subjects entering the system for care. The majority of people seeking care have non-life-threatening, yet troublesome complaints. In other words, persons who are in a reasonable state of health and who are not suffering from significant illness. Therefore the relevant cohort should fit this description, not individuals who lack any clinical or laboratory issues. Our focus is to employ reference intervals to exclude disease and not to define normality. Normality in the eyes of statisticians is quite different from the word as viewed by clinical staff, yet the term is used interchangeably without concern for its ultimate use. As a result medicine today stumbles over this issue at every turn. Scientists and artists do not speak the same language. Compounding this awkward situation has been the conviction that by increasing laboratory precision and accuracy, the utility of laboratory data, reference intervals in particular, will improve clinical understanding. This has, after many years, not proven to be the case. What has become very evident, however, is that unsustainably large sums of money are being devoted to improving laboratory performance. To what end, when we are unable to grasp the significance of what is available now including published reference intervals for common test values? A realistic perspective on the value of prevailing laboratory performance, as illustrated by reference intervals, must be adopted. The obligation of laboratories, its regulators and professional groups is to create a sustainable mechanism to provide clinically usable information, in a timely and affordable manner, to our population and to those legions of less fortunate humans.