Laboratory-based investigations are subject to substantial variability arising from several sources, including differences between subjects (e.g., age, sex, and genetic variation), within-subject variation (e.g., circadian change and pathological change), variations in sample collection and handling, and laboratory measurement error [1]. In interpreting an individual patient's laboratory test results, the clinician usually compares the reported values with reference values. Inappropriate reference values may increase the risk of either unnecessary additional investigations or failure to detect underlying disease. In clinical practice, reference values are often printed by the testing laboratory on the same document as the results, although their origins are rarely specified. Reference values for a given patient are usually defined in terms of the spread of results typically encountered from similar subjects who are known to be in good health. Ideally, the ranges are derived by using statistical criteria from a random sample of comparable individuals. To ensure that the values represent those encountered in health, the results from individuals in the sample who are found to have acute or chronic disease are usually excluded. Published reference values have been derived from a variety of samples, including those from healthy volunteers, subjects attending health screening [2] or a routine medical examination [3], first-time blood donors [4], preemployment testing, and subjects in retrospective studies [5]. The extent to which each of these different sampling strategies produces reference values appropriate to any given patient is not always clear.
