Time for a holistic approach and standardization education in laboratory medicine.

The value of laboratory medicine is closely related to the impact of its laboratory services on patient outcome. The perception of patients and medical doctors regarding medical laboratory services is that diagnostic laboratories deliver accurate test results, which guarantee an unequivocal and similar risk classification, diagnosis, treatment and patient outcome across hospitals. External quality assurance (EQA) programs, which structurally evaluate laboratory test performance, demonstrate that this perception is not true, not even for routine medical tests [1–3]. This situation is undesirable because patients live in a global world, and therefore, it is essential that diagnostic test results produced in accredited medical laboratories across the globe are comparable in time and space, enabling unequivocal diagnosis, treatment, and monitoring of patients. To that end, global standardization and harmonization of medical tests should be key for sustainable patient care with universal application of reference values and decision limits, as well as preparing for future exchange and interoperability of electronic health records. Beyond the relevance of global standardization and harmonization of routine diagnostic tests, the need to standardize and harmonize tests also holds for innovative biomarkers which have the potential to become medical tests. After all, new scientific findings based on for example disruptive -omics technologies (such as genomics, transcriptomics, proteomics, and metabolomics) are expected to undergo rapid translation and should be standardized right from the outset of their development [4]. Stakeholders involved in diagnostic testing – in vitro diagnostic (IVD) industry, medical laboratories, and EQAproviders – are faced with a multitude of legislations and regulations which are not attuned to each other and variably affect medical test performance and test standardization due to varying interpretations. First, standards from authoritative bodies such as ISO 15189:2012 and ISO 17025 for accreditation of medical laboratories, and EN 14136 and ISO 17043 for accreditation of EQA/proficiency testing providers verify the competences of its target groups in a generic way, leaving room for variable interpretation. Second, guidelines from scientific organizations such as the RiliBÄK guidelines in Germany can lead the way in defining analytical requirements regarding test performance, which is the case in German medical laboratories. Third, the former European IVD directive 98/79/EC, which is currently under revision, demands traceability of test results to standards of higher order without being clear about the exact reference measurement system that is required. Finally, the review work of the Joint Committee for Traceability in Laboratory Medicine (JCTLM) – established in 2002 – is highly relevant, as JCTLM working groups periodically evaluate the potential of new reference materials, reference methods, and reference laboratories for test standardization. Unfortunately, JCTLM has no legal status and no references are made to its database either in ISO 15189:2012 and ISO 17025 or in the IVD 98/79/EC directive. Notwithstanding this confusing situation on how to standardize tests, it is assumed by regulators and legislators that IVD industry implements the metrological traceability concept in the same unequivocal way. Independent evaluation of test accuracy and interlaboratory comparability of medical test results is structurally done by EQA organizers that provide blinded EQA samples for analysis in laboratories that participate in specific EQA programs. The first EQA surveys were set up by Belk and Sunderman back in 1947 [5]. Currently, six types of EQA programs with different evaluation capabilities exist, depending on the EQA sample characteristics and the quantities intended to be measured [6]. In essence, all EQA programs aim to improve the quality of medical testing and to reduce interlaboratory variation among laboratories. Only types 1 and 2 EQA programs make use of commutable, valueassigned EQA samples, and have the capability of evaluating trueness and imprecision of medical tests. In this issue of CCLM, Infusino et al. [7] report on the progress of traceability implementation and standardization for routine enzyme measurements. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) had established Reference Measurement Procedures (RMPs) for seven frequently requested enzymes in the period 2002–2011. These IFCC-RMPs were positioned as