Constructing time‐specific reference ranges

Reference ranges which take time (such as age) into account are often required in medicine, but simple, systematic and efficient statistical methods for constructing them are lacking. A method is described which is based on low order polynomial curves (linear, quadratic or occasionally cubic), together with guidelines for when and how to apply a logarithmic transformation to the variable analysed, testing for departures from normality, and assessment of the adequacy of the reference range which is constructed from the regression line plus or minus a multiple of the standard deviation. Standard statistical packages may be used to carry out the calculations. The question of comparing two or more groups of patients is addressed. Three examples are discussed in detail.