Procedures for setting normal values

Normal occupy an important place in medical practice. The judgment regarding the presence or absence of disease and the need to perform further testing or to treat may depend importantly on whether measured patient characteristics are within limits. The types of measurements that may be of interest cover a broad spectrum, including most medical and laboratory assessments. Frequently, however, the quality of the available reference values are far from ideal, mainly because of unrepresentative selection of healthy subjects, inadequate sample size, lack of medical evaluation of subjects, failure to also measure other variables that influence the attribute studied, and failure to rigorously apply appropriate statistical analysis. Developing better normal values might result in more sensitive (detection of disease when it is present) and specific (not detecting disease when it is absent) identification of disease. Having better reference values even for such established tests as nerve conductions might result in tangible improvements in the value of the test. The approaches we will describe might also serve to create quality reference values for newly introduced measured phenomena and tests to be used in medical practice, epidemiologic research, and controlled clinical trials. In the following sections, we discuss clinical characteristics and laboratory measurements for which normal values might be needed, why a representative sample of subjects from a population is best, the deletions from this cohort that should be considered, additional variables that might also be assessed, and the specific statistical steps used to estimate variable-specific percentile values. This article is fashioned as a didactic guide. The insights are intuitive or practical extensions from consideration of scientific and statistical concepts. We provide a short list of references for background reading 1-15 and cite specific additional studies related to the examples we include. Tests and clinical phenomena for which reference limits can …