Methods for indirect determination of reference intervals

A method for providing and using a reference interval for an analyte to aid in evaluation of test subject's test result for the analyte, comprising:

• (a) pooling data from a database in which measurements of the analyte from a reference population have been stored,
• wherein the reference population comprises both healthy and unhealthy subjects and wherein all subjects in the reference population have at least one characteristic of the test subject;
• (b) plotting cumulative frequencies of data against a range of analyte measurements from the reference population to form a distribution;
• (c) transforming the plotted data to normalize the distribution if the mean of the plotted data is located in the first or fifth quintile of the distribution thereby resulting in transformed plotted data;
• (d) calculating a linear regression, or if transformed, the transformed plotted data, the linear regression of the plotted data resulting in a curve and a value for maximum residual error;
• wherein the linear regression is constrained so that the maximum residual error of the linear portion of the curve is below a predetermined threshold to account for a within-individual biological variation for the analyte;
• (e) selecting a linear portion of the curve and determining a reference interval for the analyte in the reference population;
• (f) providing a biological sample from the test subject having the at least one characteristic used to select the reference population;
• (g) determining a measurement of the analyte in the biological sample;
• and
• (h) comparing the measurement of the analyte in the biological sample to the reference interval of step (e).