ON THE CALCULATION OF REFERENCE CHANGE VALUES, WITH EXAMPLES FROM A LONG-TERM STUDY

Reference change values (sometimes called critical differences) indica te statistically important changes between test values obtained on two occasions. They are commonly computed from the median (or mean) withi n-subject variance observed in repeated test measurements on a number of subjects. With this computational approach, all observed within-sub ject variances are assumed to be estimates of a constant true variance , the same for all individuals. Moreover, any possible correlation bet ween successive values is almost always ignored. This simplified metho dology differs from the method originally proposed for computing refer ence change values, which accounts for variability in true variances a nd for serial correlation. From data obtained from repeated measuremen ts over 2 to 5 years in 72 physically healthy subjects, we computed an d compared reference change values in 18 serum analytes, using the sim plified method and the originally proposed procedure. Although the ori ginal method is more complicated and requires a computer program, we b elieve that it produces more-reliable reference change values than tho se obtained by the simplified approach. The former are generally large r, but remain sensitive to clinically important changes in the individ ual.