Influence of index of individuality on false positives in repeated sampling from healthy individuals.

The index of individuality is defined as the ratio of the within-subject biological variation to the between-subject variation, i.e., the variation between the biological set-points. It has been disputed whether the index of individuality has influence on the usefulness of conventional population-based reference intervals. In this investigation we found that, as long as only a single sample is taken, for a certain change in an individual's set-point, the index of individuality has no influence on the usefulness of reference intervals. When two or more samples are taken into account, however, the outcome of the measurement is highly dependent on the index of individuality. For a low index, repeat measurement has only limited effect on the fraction of false-positive results, as the next result will be close to the first, but, when the index is high, the fraction of false-positive results will be reduced considerably through repeating the test. Moreover, the distribution of biological set-points for which the fraction of false-positive results originate is described and the influence of analytical imprecision is discussed. The calculations are performed for values of the index of individuality from 0 to 2.0 for the traditional 95% reference interval based on x +/- 2*s(total) (s(total) = total biological variation), and also for a decision limit (cut-off point) x +/- 3*s(total). The numbers are, of course, different, but the effects of the index of individuality are the same, independent of the chosen cut-off point. This concept is related to the clinical classification (diagnosis, prognosis, screening) and the difference from different principles of monitoring is discussed. Further, five examples are evaluated and aspects of index of individuality in relation to false-positive results are discussed.