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 la boratory. It is assumed that these reference intervals are calculated from the results of tests done on healthy individuals, and, except whe n noted, apply to people of both genders and any age, race, or body bu ild. While analyzing data from a large screening project, we had reaso n to question these assumptions. METHODS. The results of 20 serum chem istry tests performed on 8818 members of a state health insurance plan were analyzed. Subgroups were defined according to age, race, sex, an d body mass index. A very healthy subgroup (n=270) was also defined us ing a written questionnaire and the Duke Health Profile. Reference int ervals for the results of each test calculated from the entire group a nd each subgroup were compared with those recommended by the laborator y that performed the tests and with each other. Telephone calls were m ade to four different clinical laboratories to determine how reference intervals are set, and standard recommendations and the relevant lite rature were reviewed RESULTS. The results from our study population di ffered significantly from laboratory recommendations on 29 of the 39 r eference limits examined, at least seven of which appeared to be clini cally important. In the subpopulation comparisons, ''healthy'' compare d with everyone else, old (greater than or equal to 75 years) compared with young, high (greater than or equal to 27.1) compared with low bo dy mass index (BMI), and white compared with nonwhite, 2, 11, 10, and 0 limits differed, respectively. None of the contacted laboratories we re following published recommendations for setting reference intervals for clinical chemistries. The methods used by the laboratories includ ed acceptance of the intervals recommended by manufacturers of test eq uipment, analyses of all test results from the laboratory over time, a nd testing of employee volunteers. CONCLUSIONS. Physicians should reco gnize when interpreting serum chemistry test results that the referenc e intervals provided may not have been determined properly. Clinical l aboratories should more closely follow standard guidelines when settin g reference intervals and provide more information to physicians regar ding the population used to set them. Efforts should be made to provid e appropriate intervals for patients of different body mass index and age.