Extra-analytical sources of uncertainty: which ones really matter?

Since the endorsement by ISO15189:2012 of measurement uncertainty (MU) for the estimation of error in measurement procedures, the debate has been ongoing with questions concerning which method should be used for estimating MU and the benefits of using MU over other error methods. However, only limited attention has been given to extra-analytical sources of uncertainty and, currently, a clear standpoint is still missing. This opinion paper aims to evaluate whether extra-analytical variables could be included in MU. Considering coagulation tests as an example, the possible sources of preanalytical variations are evaluated by using a fishbone diagram. After excluding preanalytical errors, additional sources of uncertainty are divided into amenable to standardization/harmonization and/or possible random sources, which are not standardizable nor harmonizable. Finally, sources of uncertainty are evaluated for a possible inclusion into MU. In addition, postanalytical uncertainty is discussed, particularly considering the laboratory results calculated through a mathematical equation, derived from one or more quantities affected by their specific uncertainty.