The quest for equivalence of test results: the pilgrimage of the Dutch Calibration 2.000 program for metrological traceability

Abstract

Calibration 2.000 was initiated 20 years ago for standardization and harmonization of medical tests. The program also intended to evaluate adequate implementation of the In Vitro Diagnostics (IVD) 98/79/EC directive, in order to ensure that medical tests are fit-for-clinical purpose. The Calibration 2.000 initiative led to ongoing verification of test standardization and harmonization in the Netherlands using commutable external quality assessment (EQA)-tools and a type 1 EQA-design, where feasible. National support was guaranteed by involving all laboratory professionals as well as laboratory technicians responsible for EQA and quality officers. A category 1 EQA-system for general chemistry analytes, harmonizers for specific analytes like hGH and IGF-1, and commutable materials for other EQA-sections have been developed and structurally introduced in the EQA-schemes. The type 1 EQA-design facilitates the dialogue between individual specialists in laboratory medicine and the IVD-industry to reduce lot-to-lot variation and to improve standardization. In such a way, Calibration 2.000 sheds light on the metrological traceability challenges that we are facing and helps the laboratory community to get the issues on the table and resolved. The need for commutable trueness verifiers and/or harmonizers for other medical tests is now seen as paramount. Much knowledge is present in the Netherlands and for general chemistry, humoral immunology and protein chemistry, a few endocrinology tests, and various therapeutic drug monitoring (TDM) tests, commutable materials are available. Also the multi sample evaluation scoring system (MUSE) and the category 1 EQA-design offer many possibilities for permanent education of laboratory professionals to further improve the between and within laboratory variation and the test equivalence.

An updated protocol based on CLSI document C37 for preparation of off-the-clot serum from individual units for use alone or to prepare commutable pooled serum reference materials

“…Although out of scope for the original C37 protocol, literature reports starting with the C37 protocol or very similar protocols have shown that supplementing a serum pool with a number of analytes has produced pools with elevated concentrations with acceptable commutability properties [11,12].…”

Harmonization of External Quality Assessment Schemes and their role – clinical chemistry and beyond

“…Unfortunately, with the exception of a few examples [10][11][12][13][14], category 1 schemes remain scarce and so the real benefit of participation in EQAS remains modest. Other areas of laboratory medicine, where the experience of EQAS is more recent and/or deals with different type of measures, seem to benefit more from the participation in EQAS as reported for immunophenotyping [15] or microbiology [16].…”

“…In the Netherlands, the Calibration 2.000 initiative is a nationwide program, established in 1998, which strived for either standardization or harmonization of tests in domains beyond clinical chemistry such as hematology, endocrinology, coagulation, immunology, TDM, parasitology, etc. [11]. The output of its research was fed into the EQAS of the Dutch SKML and is reviewed in this special issue [11].…”

Metrological traceability and harmonization of medical tests: a quantum leap forward is needed to keep pace with globalization and stringent IVD-regulations in the 21st century!

“…Since 1947, attempts have been made to improve interlaboratory comparability of test results. History and updates have been described by renowned authors in recent editorials or other peer-reviewed literature [6][7][8][9]. Notwithstanding major scientific advances, appearance of international guidelines (global harmonization task force, ISO-guidelines, …) and landmark legislation (e.g.…”