Estimation of individual reference intervals in small sample sizes.
In occupational health studies, the study groups most often comprise healthy subjects performing their work. Sampling is often planned in the most practical way, e.g., sampling of blood in the morning at the work site just after the work starts. Optimal use of reference intervals requires that the population, on which the reference interval is based, is representative for the study group in question. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommends estimating reference interval on at least 120 subjects. It may be costly and difficult to gain group sizes of that order of magnitude for all topics in question. Therefore, new methods to estimate reference intervals for small sample sizes are needed. We present an alternative method based on variance component models. The models are based on data from 37 men and 84 women taking into account biological variation from various variables such as gender, age, BMI, alcohol, smoking, and menopause. The reference intervals were compared to reference intervals calculated using IFCC recommendations. Where comparable, the IFCC calculated reference intervals had a wider range compared to the variance component models presented in this study. The presented method enables occupational health researchers to calculate reference intervals for specific groups, i.e. smokers versus non-smokers, etc. In conclusion, the variance component models provide an appropriate tool to estimate reference intervals based on small sample sizes.
Hansen
Ase Marie
AM
National Research Centre for the Working Environment, Lersø Parkallé 105, 2100 Copenhagen, Denmark. aamh@nrcwe.dk
Garde
Anne Helene
AH
Eller
Nanna Hurwitz
NH
D000328:Adult; D000367:Age Factors; D003627:Data Interpretation, Statistical; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016272:Occupational Health / Q000706:statistics & numerical data*; D012016:Reference Values; D018401:Sample Size; D012737:Sex Factors