Biological and Analytic Components of Variation in Long-Term Studies of Serum Constituents in Normal Subjects

Abstract

Biological components of variation for each of 15 serum constituents have been estimated in 68 normal subjects by weekly measurements over several months, and concurrent measurements on invariant human serum pools. Intra-individual coefficient of variation was smallest, less than 2%, for Na, Cl, Ca, Mg; 3 to 4% for CO2, albumin, and total protein; 5 to 7% for K, glucose, cholesterol, and phosphate; and largest, 9 to 12%, for uric acid, urea nitrogen, SGOT, and LDH. Inter-individual variation was larger than intra-individual variation for all 15 tests except Cl, CO2, and K. Analytic deviation was as large as or larger than biological (intra- or inter-individual) variability for constituents, such as calcium, which are under precise homeostatic control, thus producing artifactual widening in the observed normal range and obscuring the borderline between normal and abnormal results. Limits of tolerable variability in laboratory procedures are proposed, based on composite intra- and inter-individual variation, that would permit medically significant deviations in results to be detected. Such limits were exceeded by current methodology in at least half the 15 tests.