Defining laboratory reference values and decision limits: populations, intervals, and interpretations

Abstract

This article provides a brief overview of various approaches that may be utilized for the analysis of human semen test results. Reference intervals are the most widely used tool for the interpretation of clinical laboratory results. Reference interval development has classically relied on concepts elaborated by the International Federation of Clinical Chemistry Expert Panel on Reference Values during the 1980s. These guidelines involve obtaining and classifying samples from a healthy population of at least 120 individuals and then identifying the outermost 5% of observations to use in defining limits for two-sided or one-sided reference intervals. More recently, decision limits based on epidemiological outcome analysis have also been introduced to aid in test interpretation. The reference population must be carefully defined on the basis of the intended clinical use of the underlying test. To determine appropriate reference intervals for use in male ferti lity assessment, a reference population of men with documented time to pregnancy of < 12 months would be most suitable. However, for epidemiological assessment of semen testing results, a reference population made up of unselected healthy men would be preferred. Although reference and decision limits derived for individual semen analysis test results will undoubtedly be the interpretational tools of choice in the near future, in the long term, multivariate methods for the interpretation of semen analysis alone or in combination with information from the female partner seem to represent better means for assessing the likelihood of achieving a successful pregnancy in a subfertile couple.

The Canadian laboratory initiative on pediatric reference intervals: A CALIPER white paper

“…Importantly, it highlights that the first step of selecting appropriate reference individuals largely determines the quality of the resulting reference interval [21]. Reference sample groups should be established by direct sampling of reference individuals from the age group(s) of interest using defined inclusion and exclusion criteria.…”

Reference limits: limited references in laboratories worldwide

“…To my knowledge, no valid and well-controlled data regarding semen from men whose partners had conceived within the preceding 12 months have been collected from these unrepresented regions. Profound comments on this regard have been made and published in the Special Issue in Asian Journal of Andrology on "Semen analysis in 21st Century Medicine" in Issue 1 in 2010 [2][3][4][5]. In this letter, I would like to present some of my views and suggestions on reference limits of semen parameters.…”

Laboratory Reference Intervals in Africa

“…This is erroneously interpreted that 95% of diseased individuals would fall outside the derived reference interval. It is recommended that the number of diseased individuals who fall outside the defined 95% reference intervals be determined through a study of the distribution of such persons with the target condition [14]. Thus, it is necessary to confirm the validity of the proposed reference intervals with clinicians using a particular test to manage patients.…”