Determination of reference intervals for 26 commonly measured biochemical analytes with consideration of long-term within-individual variation.
BACKGROUND
A reference interval (RI) is usually derived from a data set obtained cross-sectionally without consideration of the long-term analytical coefficient of variation (CV) (CV(A)) or within-individual CV (CV1).


METHODS
A total of 135 healthy volunteers, 22-59 years of age, working in eight clinical laboratories in Japan participated in a study to determine RIs for 26 commonly measured biochemical analytes. Blood samples were collected monthly for 1 year and measured in each laboratory. Common quality control (QC) specimens were measured monthly. RIs were derived parametrically using a modified Box-Cox power transformation method. Subjects with abnormal results for test items other than the one for derivation were excluded.


RESULTS
Although there was no statistically significant between-month variation, unacceptably large between-laboratory differences were observed in QF test results. Thus, all values were transformed to those of the main laboratory based on cross-check test results. CV1 values computed by two-level nested analysis of variance were generally greater than those commonly cited in the literature. Average RIs derived from the monthly results agreed well with those derived from the entire results. However, CVs of lower and upper limits of the monthly RIs were greater than CV(A).


CONCLUSIONS
To derive reliable RIs, it is important to consider long-term variability of CV1 and CV(A).
Matsubara
Akemi
A
1Clinical Laboratory, Hiroshima University Hospital, Hiroshima, Japan.
Ichihara
Kiyoshi
K
Fukutani
Shunji
S
D000328:Adult; D001774:Blood Chemical Analysis / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D015203:Reproducibility of Results; D013995:Time