All you wanted to know aboutlaboratory tests, but were afraid to

ask

By Dietmar StöcklSTT Consulting

- 8 -

The informed patient meeting the laboratory director

Standardization & TraceabilityThe solution

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Today

The reference measurement system

Now it moves forward!

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The reference measurement system

Requirements to obtain–and maintain–a meaningful

measurement system

Cali JP. Clin Chem 1973;19:291–3.

Part 1. A rational, self-consistent system of units of measurement

(e.g., the SI units).

Part 2. The materials to realize in daily practice the defined units

and their derivatives (e.g., the certified Standard Reference

Materials produced and issued by NBS = NIST).

Part 3. The availability of accurate methods of measurement,

analysis, or test, based on the well-characterized materials of part

2 (these accurate methods are often referred to as "referee

methods", "reference methods", or "standard methods").

Part 4. Field or applied methods of measurement, analysis, or test.

Part 5. A method whereby the long-term integrity of the

measurement system is assured.

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The reference measurement system

ISO 17511:2003

In vitro diagnostic medical devices –

Measurement of quantities in biological

samples – Metrological traceability of values

assigned to calibrators and control materials.

What did you take so long?

June 2002

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Traceability chain ISO 17511

Gravimetry

Assay xyzmaster procedure

Assay xyzend user’s procedure

Cortisol calibrator(NIST SRM 921 in ethanol)

Product calibrator6 calibrators

Routine sample

Material

ProcedureUnit realization

Cortisol NIST SRM 921

Patient xyz*** nmol/L

ID-GC/MS

Working calibratorHuman sera IRMM/IFCC 451

Measurand/SISerum/plasma–cortisol; amount-of-substance concentration (nmol/L)

Uncertainty

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I type ...

36 – Congratulations!

... an idea whose time has come … Cali JP. Clin Chem 1973;19:291–3

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The next visit

... heavy load!

Analytical performance goals

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ResourcesMy personal opinion is that it is almost certain that the Product Standards soon to be promulgated by the Food and Drug Administration with regard to the labeling requirements of clinical kits, chemicals, and devices will, where applicable, somehow relate to and (or) require the use of referee methods (or state-of-the-art interim methods where referee methods have not yet been developed) to provide the baseline against which other methods or products will be assessed.

Cali JP. An idea whose time has come$. Clin Chem 1973;19:291–3 ($accuracy in clinical chemistry)

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ResourcesISO Guide 2:2004 Standardization and related activities — General vocabulary1.1 standardization: activity of establishing, with regard to actual or potential problems, provisions for common and repeated use, aimed at the achievement of the optimum degree of order in a given context; NOTE 1 In particular, the activity consists of the processes of formulating, issuing and implementing standards; NOTE 2 Important benefits of standardization are improvement of the suitability of products, processes and services for their intended purposes, prevention of barriers to trade and facilitation of technological cooperation.1.4 state of the art: developed stage of technical capability at a given time as regards products, processes and services, based on the relevant consolidated findings of science, technology and experience.

2 Aims of standardizationNOTE The general aims of standardization follow from the definition in 1.1. Standardization may have one or more specific aims, to make a product, process or service fit for its purpose. Such aims can be, but are not restricted to, variety control, usability, compatibility, interchangeability, health, safety, protection of the environment, product protection, mutual understanding, economic performance, trade. They can be overlapping.2.1 fitness for purpose: ability of a product, process or service to serve a defined purpose under specific conditions.2.2 compatibility: suitability of products, processes or services for use together under specific conditions to fulfil relevant requirements without causing unacceptable interactions2.3 interchangeability: ability of one product, process or service to be used in place of another to fulfil the same requirements; NOTE The functional aspect of interchangeability is called “functional interchangeability”, and the dimensional aspect “dimensional interchangeability”.2.4 variety control: selection of the optimum number of sizes or types of products, processes or services to meet prevailing needs; NOTE Variety control is usually concerned with variety reduction.2.5 safety: freedom from unacceptable risk of harm; NOTE In standardization, the safety of products, processes and services is generally considered with a view to achieving the optimum balance of a number of factors, including non-technical factors such as human behaviour, that will eliminate avoidable risks of harm to persons and goods to an acceptable degree.

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ResourcesMore definitions of standardization

Merriam Webster's Online DictionaryStandardization (main entry: standardize)Standardize1 : to compare with a standard 2 : to bring into conformity with a standard

NATO definition of standardization"The development and implementation of concepts, doctrines, procedures, and designs to achieve and maintain the required levels of compatibility, interchangeability or commonality in the operational, procedural, materiel, technical and administrative fields to attain interoperability. Note: the three levels of standardization in ascending order are: compatibility, interchangeability and commonality (AAP 6 4/10/2000)".

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Resources (VIM)metrological traceabilityproperty of a measurement result whereby theresult can be related to a reference through adocumented unbroken chain of calibrations, eachcontributing to the measurement uncertainty

NOTE 1 For this definition, a ‘reference’ can be a definition of a measurement unit through its practical realization, or a measurement procedure including the measurement unit for a non-ordinal quantity, or a measurement standard.

NOTE 2 Metrological traceability requires an established calibration hierarchy.

measurement standard (etalon)realization of the definition of a given quantity, withstated quantity value and associated measurementuncertainty, used as a reference.

commutability of a reference materialproperty of a reference material, demonstrated bythe closeness of agreement between the relationamong the measurement results for a statedquantity in this material, obtained according to twogiven measurement procedures, and the relationobtained among the measurement results for otherspecified materials

NOTE 1 The reference material in question is usually a calibrator and the other specified materials are usually routine samples.

NOTE 2 The measurement procedures referred to in the definition are the one preceding and the one following the reference material (calibrator) in question in a calibration hierarchy (see ISO 17511).

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ResourcesIn vitro diagnostic medical device directive 98/79/EC(and related CEN TC 140 and ISO TC 212 activities)http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:1998:331:0001:0037:EN:PDFhttp://www.newapproach.org/Directives/DirectiveList.asphttp://www.cen.eu/newapproach/cen/stdlist.asp?dir_area=98/79/EC&prod_fam=CEN/TC%20140http://www.iso.org/iso/iso_catalogue/catalogue_tc/catalogue_tc_browse.htm?commid=54916&published=on

JCTLM (Joint committee for traceability in laboratory medicine)http://www.bipm.org/en/committees/jc/jctlm/

IFCC working groups and committees related to standardizationhttp://www.ifcc.org/index.asp?cat=Scientific_Activities&scat=Working_Groups&rif=4&dove=1http://www.ifcc.org/index.asp?cat=Scientific_Activities&scat=Committees&rif=4&dove=1

Centers for disease control and prevention (activities related to standardization in laboratory medicine)http://www.cdc.gov/nceh/dls/

Interdipartimental Center of Metrological Traceability in Laboratory Medicine http://users.unimi.it/cirme/home/index.php

Clinical and laboratory standards institute (CLSI)http://www.clsi.org

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ResourcesReference materialshttps://www-s.nist.gov/srmors/BrowseMaterials.cfm?subkey=5&category=1 (NIST)http://irmm.jrc.ec.europa.eu/html/homepage.htm (IRMM)http://www.reccs.or.jp/e_activities.htmlhttp://www.nibsc.ac.uk/ (NIBSC, merged into the HPA)

Established standardization activities

Lipids: http://www.cdc.gov/labstandards/lsp.htm

Steroids: http://www.cdc.gov/nceh/dls/hormone_standardization.htm

Creatinine and other kidney markers: http://www.nkdep.nih.gov/labprofessionals/

HbA1c: http://www.ngsp.org/prog/index.html; http://www.ifcchba1c.net/

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ResourcesReferences

Cali JP. An idea whose time has come. Clin Chem 1973;19:291–3.

Vesper HW, Thienpont LM. Traceability in laboratory medicine [Review]. Clin Chem 2009;55.

Thienpont LM. Accuracy in clinical chemistry - who will kiss Sleeping Beauty awake? Clin Chem Lab Med 2008;46:1220-2.

Thienpont LM, Van Uytfanghe K, De Leenheer AP. Reference measurement systems in clinical chemistry [Review]. Clin Chim Acta 2002;323:73-87.

Stöckl D, Franzini C, Kratochvíla J, Middle J, Ricós C, Thienpont LM. Current stage of standardization of measurements of specific polypeptides and proteins discussed in light of steps needed towards a comprehensive measurement system. Eur J Clin Chem Clin Biochem 1997;35:719-32.