The determination and interpretation of reference intervals for multichannel serum chemistry tests.

BACKGROUND: When interpreting the results of clinical chemistry tests, physicians rely heavily on the reference intervals provided by the laboratory. It is assumed that these reference intervals are calculated from the results of tests done on healthy individuals, and, except when noted, apply to people of both genders and any age, race, or body build. While analyzing data from a large screening project, we had reason to question these assumptions.
METHODS: The results of 20 serum chemistry tests performed on 8818 members of a state health insurance plan were analyzed. Subgroups were defined according to age, race, sex, and body mass index. A very healthy subgroup (n = 270) was also defined using a written questionnaire and the Duke Health Profile. Reference intervals for the results of each test calculated from the entire group and each subgroup were compared with those recommended by the laboratory that performed the tests and with each other. Telephone calls were made to four different clinical laboratories to determine how reference intervals are set, and standard recommendations and the relevant literature were reviewed.
RESULTS: The results from our study population differed significantly from laboratory recommendations on 29 of the 39 reference limits examined, at least seven of which appeared to be clinically important. In the subpopulation comparisons, "healthy" compared with everyone else, old (> or = 75 years) compared with young, high (> or = 27.1) compared with low body mass index (BMI), and white compared with nonwhite, 2, 11, 10, and 0 limits differed, respectively. None of the contacted laboratories were following published recommendations for setting reference intervals for clinical chemistries. The methods used by the laboratories included acceptance of the intervals recommended by manufacturers of test equipment, analyses of all test results from the laboratory over time, and testing of employee volunteers.
CONCLUSIONS: Physicians should recognize when interpreting serum chemistry test results that the reference intervals provided may not have been determined properly. Clinical laboratories should more closely follow standard guidelines when setting reference intervals and provide more information to physicians regarding the population used to set them. Efforts should be made to provide appropriate intervals for patients of different body mass index and age.