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Keywords: reference intervals, decision limits, reference subjects, validation
References, and their myriad forms and derivations, are a principle theory in every medical discipline, including device and drug development studies. The concept of reference values encompasses more than the ubiquitous population-based reference intervals (RI). At one end of the spectrum we have universal reference intervals, and at the other end, subject-based homeostatic set-points and reference change values (RCV), with subgroup reference intervals based on physiologic characteristics lying somewhere in between. An alternative decision-making criterion is a decision limit. Each has advantages, shortcomings, and challenges with regards to laboratory effort and decision-making properties. Furthermore, reference values and decision limits are specific to a particular method and quality of analysis. The intention of this introductory presentation is to bring attention to the most important aspects of selecting a decision criterion, identifying relevant subjects, applying appropriate statistical analysis, and validating the decision criterion for a new population.