Rationale for Reference Methods in Clinical Chemistry

In the field of clinical chemistry evidence is mounting that a reliable and medically relevant structure can be built on the concept of compatibility through accuracy in measurement. By compatibility is meant the ability of all laboratories in a network to achieve on a given sample similar and reliable numerical values for a property under test. It is shown that when all laboratories in a network are making accurate measurements, i.e. free of systematic error and precise, then compatibility automatically ensues. The need for accurate measurement based on medical arguments is given. In order to build an accurate measurement network, three measurement methodology levels and three types of reference materials are required. A definitive method is directly able to realize or to have access to the base or derived units of the measurement system. It depends in part on the availability of pure reference materials. (E.g. those supplied by the National Bureau of Standards and called SRM's.) At the next level are reference methods and matrix reference materials. These methods and materials are more adapted to implementation and use by clinical reference laboratories and the manufacturers of secondary reference materials. In turn these materials are used at the local level to control the quality and accuracy of the routine methods. How this hierarchy of methods and reference materials is structured is discussed. The role of the definitive method is discussed in some detail, because of its crucial place in the structure. Potentially useful definitive methods, both for inorganic and organic constituents are outlined. A discussion of reference method developments, per se, is left to the other three authors of this Symposium (qv). Clinical SRM's now available are listed, as well as those now in preparation at NBS. The need for matrix reference materials is stated. Finally, how this measurement network should be structured and implemented together with suggested organizations responsible for the various levels is discussed.