Provisional recommendation on the theory of reference values (1978). Part 1. The concept of reference values.
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Biomedical subjects
Publications and source records attributed to G Z Williams.
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Assessment of the significance of an observed set of serum chemical values for determining a person's state of health requires comparison with a set of defined reference values. We tested the assumption that a reference group of individuals, categorized by age and sex, gives a narrower range of variation than does a larger mixed population. If this were true, the demographic set would be a more sensitive reference than is the customary "normal range" for interpretation of values occurring in the individual. The ratio, R, of intra-personal to inter-personal (group) standard deviations was similar for defined age/sex classes and the overall group for 16 serum constituents. When the "raw" intra-individual variation (biological plus analytical variation) was adjusted to remove the average analytical component, the resulting R was less than 80 for all constituents except creatine kinase, which indicates that these are all particularly strong "discriminators" of individuality. These results imply the need for individual rather than population-based reference ranges, even if the latter are from persons of similar age and the same sex.
Variation in the assays of uniform control serum commonly are assumed to represent day-to-day analytical variation. To test this assumption, we compared the differences between results of serum aliquots assayed immediately for 12 constituents and frozen aliquots accumulated and assayed on a single day with the results of control serum variation from the same period. One aliquot of each weekly sample was stored frozen. Eleven subjects were sampled for 12 weeks. Storage at --20 degrees C for 15 weeks had a mild destructive effect on two enzymes in serum. The control serum data revealed significant linear trends in magnesium (upwards) and alkaline phosphatase (downwards) that substantially increased the respective variances. In the other 10 constituents tested, comparison of variances indicated that long-term (weeks) variation in control serum assays is similar to the difference of variation between aliquots assayed immediately and those frozen and assayed at the same time. For these constituents, this finding justifies the use of control serum to estimate long term analytical variation.
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