Reference intervals (normal ranges) not speed limits

Sometimes we forget what we learned in pre-Med. There is variability in most tests we order from the clinical chemistry laboratory and some tests are more variable than others. All too often we think that any lab value that is outside the lab's stated reference interval represents a disease process and needs further evaluation. That brings to mind two problems. Normal ranges only encompass the 95% confidence limits, such that 5% of the time perfectly healthy normal folks will have an abnormal lab result. Secondly, and perhaps more importantly, lab results and reference intervals may vary widely from lab to lab simply because the same test can be measured by any one of several good assays.

The February 2008 issue of Clinical Chemistry has an important editorial from Jim Boyd, MD, pointing out that the search for uniformity for assays from lab to lab remains elusive. It is important to have serial tests done in the same lab so that changes in the assay method or normal ranges don't give us misleading information. I could not find an online link to the full-text of the editorial for non-members of the American Association of Clinical Chemists (AACC) but your local medical library and/or your chemistry lab is sure to have a copy. Read the editorial and the other articles in the same issue that the editorial cites to see how this might directly affect your day-to-day clinical practice.

To underscore this point, the Centers for Disease Control and Prevention is holding a two-day meeting next week (March 17-18, 2008) to discuss in detail the many issues that plague testosterone assays. Later in the week, the College of American Pathologists is having a teleconference to address similar issues.

I am not sure what has sparked this flurry of activity related to lab assays, but I am sure that this is something we all need to think about on a daily basis.

Let me know some of the cases that have been referred to you because of this non-transportability of lab assays.