Introduction to Clinical Laboratory Testing

Basic Statistical Considerations

Reference Ranges
Results are most typically interpreted with respect to the range of values found in
normal, clinically healthy individuals. A result is considered abnormal if the value is
less than the lower limit of the normal range or is greater than the upper limit. Normal
ranges are determined from measurements on specimens from a large number
(several hundred) of clinically normal individuals. When results are plotted in
histogram fashion a distribution such as that illustrated below is obtained.

The normal range, or reference range, is determined by lower and upper limit values,
as represented by test result values A and B in the figure to the right, which include
95% of all of the values. The distribution of values, in many cases, is Gaussian, bell-
shaped, or uniform, as in the figure, and the normal range is relatively easily
determined from the mean value and the standard deviation (S.D.), i.e.:

lower limit (A) = mean value - 2 S.D.

upper limit (B) = mean value + 2 S.D.Not all test results from a clinically normal
population distribute uniformally. Total bilirubin is an example and in such cases a
more tedious, nonparametric procedure must be used to determine the lower and
upper limits which include 95% of the population.
In some cases the upper and lower limits comprising 95% of a normal population is
not the appropriate refence range. Total serum cholesterol is a case in which the
usually quoted reference range is determined as a "healthy" range on the basis of
results from long term epidemiologic studies, such as the Framingham study. In other
cases, of which serum creatinine is an example, it is most appropriate to compare a
current value to a previously determined value. Similarly, endocrinologic testing is
often based upon comparing test results before and after administration of a stimulus
or inhibitor. In general, pathology is often effectively evaluated on the basis of
monitoring changes in laboratory values.