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External Quality Assessment Scheme for reference laboratories – review of 8 years’ experience

  • Anja Kessler EMAIL logo , Lothar Siekmann , Cas Weykamp , Wolf Jochen Geilenkeuser , Orna Dreazen , Jonathan Middle and Gerhard Schumann
Published/Copyright: January 18, 2013
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Clinical Chemistry and Laboratory Medicine
From the journal Clinical Chemistry and Laboratory Medicine Volume 51 Issue 5

Abstract

We describe an External Quality Assessment Scheme (EQAS) intended for reference (calibration) laboratories in laboratory medicine and supervised by the Scientific Division of the International Federation of Clinical Chemistry and Laboratory Medicine and the responsible Committee on Traceability in Laboratory Medicine. The official EQAS website, RELA (www.dgkl-rfb.de:81), is open to interested parties. Information on all requirements for participation and results of surveys are published annually. As an additional feature, the identity of every participant in relation to the respective results is disclosed. The results of various groups of measurands (metabolites and substrates, enzymes, electrolytes, glycated hemoglobins, proteins, hormones, thyroid hormones, therapeutic drugs) are discussed in detail. The RELA system supports reference measurement laboratories preparing for accreditation according to ISO 17025 and ISO 15195. Participation in a scheme such as RELA is one of the requirements for listing of the services of a calibration laboratory by the Joint Committee on Traceability in Laboratory Medicine.

Keywords: external quality assessment scheme; reference measurement procedure; traceability

Introduction

Whenever possible, standardization of measurement results in laboratory medicine requires the implementation of the concept of traceability. Accordingly, reference measurement laboratories (RML) have been established which provide services to organizers of External Quality Assessment Schemes (EQAS) for routine laboratories, and to test kit manufacturers who wish to demonstrate traceability of the results of their routine test procedures as required in EU Directive 98/79, Annex 1.

It is essential that such reference measurement service providers demonstrate their competence in a particular EQA system designed for reference/calibration laboratories. Until 2003, no such EQAS for RML existed. Therefore, the Scientific Division Executive of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) launched a ring trial system in order to support the activities of the Joint Committee on Traceability in Laboratory Medicine (JCTLM) and the IFCC Committee for Traceability in Laboratory Medicine (C-TLM) was established. The main task of C-TLM is provision and further development of an EQAS for reference laboratories, the so-called RELA. Furthermore, C-TLM acts as the international advisory board for RELA surveys. These are organized by an experienced national proficiency testing organizer (Reference Institute for Bioanalytics, Germany, RfB) [1].

RELA provides a platform for RML to regularly demonstrate their competence. The results of the ring trial provide important data for the accreditation process according to ISO 15195 [2] and are an essential criterion for being listed in the JCTLM data base [3]. Consequently, RMLs must not only demonstrate official accreditation but should also make use of RELA services.

The ring trial results may also be used to demonstrate equivalence or even discordance of different reference measurement procedures [1]. The resulting discussions may in fact lead to improvement of reference system.

It is generally expected that laboratories apply reference measurement procedures according to ISO 15193 [4] and as listed in JCTLM list 1 [3]. However, candidate laboratories which are investigating a new analytical principle in order to establish a new reference measurement procedure are also invited to participate. Comparison with established services might be important for the development and validation of this new procedure. Results from laboratories that obviously perform routine procedures instead of reference methodology will be excluded from the evaluations [1].

Laboratories of the National Metrology Institutes (NMI) known to provide reference measurement procedures of the highest order are also invited to participate in RELA. RELA surveys can visualize links between RMLs and NMIs and can demonstrate traceability to the top of the metrological hierarchy.

To date, RELA ring trials are provided for 34 measurands divided into seven groups: metabolites and substrates, enzymes, electrolytes, glycated hemoglobins, proteins, hormones, thyroid hormones, and therapeutic drugs.

Method

The official website of RELA (www.dgkl-rfb.de:81) [5] is accessible to all. The published information is intended for participants and any other interested parties. A link to the IFCC-RELA-EQAS procedure manual describing scope, rules, and decision criteria can be found on the homepage. An additional web manual provides instructions for registration, ordering, and entering of results. Since 2003, RELA surveys are conducted annually. Access to the evaluation of all RELA surveys since 2003 is open to all. Results of the participating laboratories are summarized in the form of tables and Youden diagrams for each measurand. Information on the results of each participating laboratory, including the related measurement uncertainty and the applied method are also published.

Each participant receives a set of two different samples for each measurand. While there is no specified protocol for the measurements, it is expected that the results are established in the manner usually employed by the RML when providing reference measurement services to a customer. Certification of a reference procedure value requires a (reasonable) number of repetitive measurements under reproducible conditions – e.g., using separate calibrations – in order to calculate an expanded measurement uncertainty. Hence, each participant receives five vials for each individual sample. The material of investigation is human serum-based and lyophilized.

The time interval between delivery of RELA samples and submission of results is approximately 6 months. Results and uncertainty parameters may be entered on the website up to a specified deadline. The organizer requests additional information, e.g., whether the reference procedure used and/or the participating laboratory is listed in the JCTLM database [3]. This information will help in the evaluation and the addition of acceptance criteria, the so-called ‘Limits of Equivalence’.

Each participant receives a printed version of a first statistical evaluation, but only for each of the submitted results. At this stage, the identity of the other laboratories remains confidential. The participants may withdraw their results within a period of 4 weeks after this first internal evaluation. If a participant does not withdraw the results within that period of time he agrees to publication of his laboratory results on the RELA website [5], after which results and identity of the laboratory are no longer confidential and the identity of the participant is disclosed. Each published result can be correlated to the respective laboratory. This additional feature is beyond the usual practice of surveys for routine laboratories.

Finally, each participant receives a certificate of participation for each published result of a measurand.

Limits of equivalence

Starting with RELA 2007, the so-called ‘Limits of Equivalence’ (LoE) were calculated and displayed in the evaluations proposing a provisional acceptance criterion (Table 1). These limits are not be considered as a ‘grading’ system and have no regulatory impact to date, since currently no ‘perfect’ method is available and discrepancies cannot be sorted out. However, the limits may be considered educational means to improve laboratory performance. The setting of these limits refers to the four-to-one rule (4:1) [6, 7]. This rule states that the results of reference measurement procedures are at least four times more accurate than the results of routine procedures to be certified and/or calibrated. Hence, the LoE are currently set to 25% of the total error performance limits for routine laboratories and the decision limits prescribed by the directive for external quality assurance for routine laboratories in Germany (RILIBÄK) [8] are presently applied. The decision limits used in EQAS for routine laboratories are set according to medical requirements and the current state of the art.

Results of at least five RMLs using a JCTLM listed procedure have to be available so that median and limits can be calculated on a statistically firm basis. The Limits of Equivalence are displayed in the Youden diagrams.

Table 1

The ‘Limits of Equivalence’ are set to one quarter of acceptable performance limits for testing (routine) laboratories. For the measurands marked witha no default values are available. Thus, the values are set as decided by C-TLM.

GroupMeasurandRELA-limits of Equivalence, %
Metabolites and substrates (META)Creatinine5.00
Glucose3.75
Total bilirubin5.50
Total cholesterol3.25
Total glycerol4.00
Urea5.00
Uric acid3.25
Electrolytes (ELEC)Calcium2.50
Chloride2.00
Lithium3.00
Magnesium3.75
Potassium2.00
Sodium1.25
Enzymes (ENZY)ALT5.25
α-Amylase5.25
AST5.25
CK5.00
GGT5.25
LDH4.50
Proteins (PROT)Total protein2.50
Hormones (HORM)17OH- progesteronea7.50
Aldosteronea8.75
Cortisol7.50
Estradiol-17β8.75
Estriola7.50
Progesterone8.75
Testosterone8.75
Thyroid hormones (THYR)Total thyroxine6.00
Total triiodothyronine6.00
Therapeutic drugs (THER)Digoxin7.50
Digitoxin7.50
Theophylline6.00
Glycated hemoglobins (GLYC)HbA1c4.50

Uncertainty of measurement

Any measurement result, no matter how accurate, has an uncertainty. Thus, every measurement result consists of the concentration or catalytic concentration (enzymes) and the declaration of the uncertainty of measurement. The accreditation process stipulates that each laboratory must state its results in this way [9]. Consequently, RELA participants have to report the results together with the combined expanded uncertainty according to the Guide to the Expression of Uncertainty in Metrology (GUM) [10]. The expanded measurement uncertainty comprises the ‘random contribution’ as calculated from repetitive measurements multiplied by the coverage factor (depending on the number of independent observations) and the ‘systematic contribution’ which may be derived from known uncertainties reported in the certificates of all calibrated devices and materials used in the analytical process (e.g., uncertainty of the purity of the calibrator material, uncertainty of the balances and test weights, uncertainty of the calibrated volumetric devices). The combined expanded measurement uncertainty shall have a probability of 95%.

The results of routine laboratories whenever reported in an EQAS are usually based on a single measurement and the performance limits (e.g., the RILIBÄK limits of acceptance of the German Federal Medical Board [8]) take into account the additional uncertainty of such a single result.

In contrast, reference/calibration laboratories report their results as a mean or median of a series of independent measurements which is of some advantage with respect to reporting the result of a single measurement. Accordingly, whenever the four-to-one rule is applied for establishing LoE for reference/calibration laboratories it should be expected that not only their final results, but also their reported expanded uncertainties are within the LoE.

Comparisons between two participants

Calibration laboratories which have become officially accredited may be interested in directly comparing their results with those from another RELA participant with official accreditation. Comparison with the results from a metrology institute could also be desired. Such a comparison can be performed by use of the following formula:

  • |DiffLab(x)-Lab(y)/√(U2Lab(x)+U2Lab(y))|≤1

  • DiffLab(x)-Lab(y): Difference of RELA results for a measurand from participant x and participant y

  • ULab(x): Combined expanded measurement uncertainty for the result from participant x

  • ULab(y): Combined expanded measurement uncertainty for the result from participant y

An overlap of the measurement uncertainties is achieved with a value ≤1. When the participants x and y have similar results for their measurement uncertainty and the calculated value according to the given formula is close to zero, the two participants are very likely measuring in the same way.

Statistics – RELA in progress

Since RELA was started in 2003 the number of participants in RELA surveys and the number of published results have continuously increased. All results obtained to date are published on the RELA website [5] with the identities of the laboratories disclosed. For example, 256 results from 48 laboratories were submitted for RELA 2010 (see Figure 1). The participating laboratories are located all over the world. And although they are not uniformly distributed, it is evident that implementation of the concept of traceability has developed into a global activity.

As the network of RML continues to grow it is currently not necessary for each country to provide a RML for each measurand. However, RMLs must be familiar with the concept of traceability and each laboratory must contribute to the implementation of traceability worldwide and provide a link between the routine laboratory and the SI unit.

Figure 1 Number of results and participants.The graphs demonstrate that the number of participants in the RELA surveys (line with squares) as well as the number of published results (line with dots) has continuously increased since RELA was launched in 2003.
Figure 1

Number of results and participants.

The graphs demonstrate that the number of participants in the RELA surveys (line with squares) as well as the number of published results (line with dots) has continuously increased since RELA was launched in 2003.

As the number of RMLs is small compared to routine laboratories, not all RMLs can participate for all measurands on each occasion. Therefore, collection of a statistically relevant number of results for each of the measurands necessary to demonstrate comparability of results from different laboratories is difficult. Consequently, the RELA organizers recommend preferable participation for one measurand (key measurand) on each occasion. A key measurand is selected for each group of measurands for each ring trial. The recommendation of the nomination of a key measurand was adhered to by many participants. For example, the RELA organizer selected potassium as the key measurand from the group of electrolytes for RELA 2008. A majority of seven laboratories accepted the recommendation of the organizer and provided results for this key measurand. This reasonable number of results forms a valid basis for a meaningful comparison. Furthermore, the addition of LoE depends on the number of at least five suitable results.

In Table 2, the numbers of participants are listed by measurand and year. The numbers highlighted in yellow identify the key measurands. The comparison of the numbers of participants for key measurands vs. the other measurands demonstrates that the ‘key measurand’ system has been accepted by the participants according to their needs.

RELA is open for RML with different levels of experience in reference methodology, and only a minority has its competence certified by official accreditation. This has to be considered when comparing the results for the same measurand.

Table 2

The numbers of RELA participants are listed by measurand and year. The numbers highlighted in red label the key measurands.

Table 2 The numbers of RELA participants are listed by measurand and year. The numbers highlighted in red label the key measurands.

Metabolites and substrates

In this category, the following measurands are provided: creatinine, glucose, total bilirubin, total cholesterol, total glycerol, uric acid, and urea. The number of participants has been continuously increasing over the years.

Creatinine

Creatinine was key measurand at RELA 2004, RELA 2005, and RELA 2010. Of note are the results for RELA 2010 creatinine. Five of the 12 participating laboratories are National Metrology Institutes (NMI). They use the organization of RELA as a platform for internal method comparison, simultaneously providing an invaluable link to the higher level in the traceability hierarchy of laboratories.

Glucose

Three different reference measurement procedures (RMP) are listed in the JCTLM database [3]. The procedures applying the principle of isotope dilution mass spectrometry or spectrophotometry, respectively, are used by RELA participants. Both collectives of results are mostly within the limits of equivalence and comparable to each other. Most participants use spectrophotometry for the hexokinase/glucose-6-phosphate dehydrogenase procedure. The calculation of the combined measurement uncertainty of the enzymatic procedure is very complex. The long-term supply with chemicals and biochemicals of constant quality is difficult to achieve. This is possibly the main reason behind the fact that the dispersion of the results is larger compared to those obtained by ID-GC/MS.

Total bilirubin

The measurand consists of four or five bilirubin species: unconjugated bilirubin, monoconjugated bilirubin, diconjugated bilirubin, bilirubin covalently bound to albumin and photobilirubin. The RMP according to Doumas et al. [11] uses spectrophotometry of the bilirubin derivatives. A revision of the RMP and measurements according to a design to which several RMLs had agreed upon revealed substantial improvement in the homogeneity of RELA results for total bilirubin [12]. Nevertheless, the published ‘Doumas procedure’ requires more standardized steps towards a better standardized RMP.

Total cholesterol

Two different RMPs are listed in the JCTLM database. One RMP is based on the principle of IDMS [13, 14]; the second is the modified ‘Abell-Kendall method’ using a color development with acetic anhydride-sulfuric acid to estimate the concentration of total cholesterol [15]. Both procedures are used in RELA for sample analysis. However, the comparison of results consistently displays a significant bias of 3%–4% between procedures (e.g., RELA 2009). From a metrological point of view, this situation does not fulfill the requirements of the traceability concept and requires a detailed discussion.

Enzymes

Catalytic concentration measurements of IFCC standardized procedures for enzymes represent the largest number of participants in RELA. For example, for AST measurements the increase from four participants in 2003 to 28 participants in 2011 indicates the need of reference methodology and respective services for enzyme measurements. The majority of the participating RMLs has not (yet) achieved official accreditation according to ISO 15195. Only four RMLs are listed with JCTLM [3]. Consequently, a comparison of all results and the LoE are influenced by different levels of competence and practical experience in reference methodology. The 2010 results for α-amylase (Figure 2) and γ-glutamyl transferase show strong correlations from the lowest to the highest pair of measurement results of all participants. This indicates systematic deviation for certain measurement parameters. These measurement parameters include, e.g., inaccurate pH adjustment for the reagent solutions of the reference measurement procedure for α-amylase, and wavelength inaccuracy for the measurement of γ-glutamyl transferase. Participants stated combined measurement uncertainties over a very large range. Some values were very small and appear to be not realistic. Other participants declaring very large measurement uncertainties might learn from the scheme that their reference measurement procedure requires improvement.

Electrolytes

A large variety of measurement principles is used for RMP for the electrolytes sodium (Na), potassium (K), total calcium (Ca) and total magnesium (Mg). The measurement principle in use for Na and K is mainly flame emission spectroscopy (FES). The measurement principle in use for Ca and Mg is mainly atomic absorption spectroscopy (AAS). The maximum number of participants for the electrolytes was 10. The data base in RELA for the reference methodology for Na, K, Ca and Mg is not sufficiently homogenous with respect to the narrow biological variation of the concentration of these analytes in human serum. Improvement of RELA results over the years was minimal. Matrix effects appear to contribute to uncertainty of measurements in human serum. One participating metrology institute is using a reference measurement procedure based on ion chromatography (IC). This higher order IC procedure is performed in samples of which all organic constituents are reduced to ashes. The combined measurement uncertainty of the IC procedure is very small. Constant participation of the metrology institute in RELA is of great benefit for the other RELA participants using FES or AAS as they can evaluate their results in one to one comparisons with the IC results.

Figure 2 RELA results for a-amylase in 2012.The results of all participants submitted for α-amylase in RELA 2010 are summarized in graphical and table form. Each dot in the diagram represents the two results of one participant. The identically colored rectangle marks the expanded uncertainty reported by the participant. The green square highlights the Limits of Equivalence. Each laboratory has its own laboratory code disclosed on the RELA website. With this code the identity of the laboratory can be correlated with its results and the method that had been applied.
Figure 2

RELA results for a-amylase in 2012.

The results of all participants submitted for α-amylase in RELA 2010 are summarized in graphical and table form. Each dot in the diagram represents the two results of one participant. The identically colored rectangle marks the expanded uncertainty reported by the participant. The green square highlights the Limits of Equivalence. Each laboratory has its own laboratory code disclosed on the RELA website. With this code the identity of the laboratory can be correlated with its results and the method that had been applied.

HbA1c

HbA1c has been included in the RELA program since 2005. Table 3 summarizes the essential results as seen in the respective years. Column 2 shows that the number of participating laboratories gradually increased from two in 2005 to eight in 2010. The third column shows the inter-laboratory coefficient of variation (CV). The mean inter-laboratory CV throughout the years is 2.3% with no clear trend. Column 4 shows the median expanded uncertainty as reported by the respective laboratories. The expanded uncertainty is expressed in percent to make it comparable from year to year. The overall mean reported expanded uncertainty is 2.5%, again with no clear trend over the years.

It is interesting to compare the expanded uncertainty as reported by the individual laboratory (intra-laboratory expanded uncertainty) with the expanded uncertainty derived from the inter-laboratory CV (inter-laboratory expanded uncertainty). An approximate value of the inter-laboratory expanded uncertainty (k=2) can be calculated by multiplying the inter-laboratory CV with a factor of 2. This is done in column 5. The last column of the table shows the ratio of inter-laboratory and intra-laboratory expanded uncertainty. It can be seen that this ratio is 1.9. This demonstrates that users of RML services (e.g., EQA organizers) should use the expanded uncertainties as reported by the RML cautiously. A user may think that the true HbA1c value with 95% confidence for a sample, to which a HbA1c target of 100 mmol/mol is assigned, is 100±2.5 mmol/mol, whereas in reality, taking into account the differences between laboratories, this is 100±4.6 mmol/mol. The same phenomenon is also demonstrated in the RELA graphs: boxes of the respective laboratories often do not overlap.

Table 3

Essential results of RELA HbA1c for the period from 2005 to 2010.

YearNumber of laboratoriesInter-lab CV, %Median intra-laboratory expanded uncertainty, %Mean inter- laboratory expanded uncertainty, %Ratio inter/intra- laboratory expanded uncertainty
201082.12.24.21.9
200962.62.25.22.4
200853.01.96.03.2
200743.22.86.42.3
200641.82.93.81.2
200521.03.02.00.7
Overall mean2.32.54.61.9

Total protein

The RMP for total protein is a spectrophotometric procedure according to Doumas et al. [16]. The method involves biuret reagent which reacts with peptide bounds of the proteins. Bovine albumin Standard Reference Material (SRM 927) from NIST is used for calibration. From a metrological point of view, the measurand total protein in human serum is not well-defined. The number of participants in RELA increased within 4 years from four to 13 participants in RELA 2011, with results in good agreement.

Steroid hormones

The following low-molecular steroids are currently provided: 17-OH-progesterone, aldosterone, cortisol, estradiol-17ß, estriol, progesterone, and testosterone. The number of participating laboratories is very low. However, even with just two participants comparison can offer valuable information for each RML. Nomination of a key measurand is of great value especially in groups like this one. For example, progesterone had been key measurand in RELA 2010 and five laboratories submitted results for publication. Since all participants used JCTLM listed procedures the criteria for implementation of the limits of equivalence were fulfilled and hence all participating laboratories could be listed. The Youden diagram (Figure 3) shows that the comparability of the results is excellent, each value including the reported expanded uncertainty was within the limits. Last, but not least, a metrology institute was also participating. Thus, the link between RML and NMI has been successfully realized. This example clearly demonstrates the idea of RELA.

Thyroid hormones

The group of thyroid hormones has been separated from the group of hormones since RELA 2010. Total triiodo-thyronine and total thyroxine are measurands of this group.

Figure 3 RELA results for progesterone in 2010.The results of all participants submitted for progesterone in RELA 2010 are summarized in graphical and table form.
Figure 3

RELA results for progesterone in 2010.

The results of all participants submitted for progesterone in RELA 2010 are summarized in graphical and table form.

The situation of participation is similar to those of the group of hormones. Although the number of participating laboratories is very low the comparison may provide valuable information to each participant.

Therapeutic drugs

This group comprises the measurands digoxin, digitoxin, and theophylline. The number of participants is low and varies from one to five. Nevertheless, the results are valuable for accreditation purposes to demonstrate comparability since there is usually more than one participant.

Conclusions and outlook

RELA, the EQA Scheme for Reference Laboratories sponsored by IFCC, makes a significant contribution to the implementation of the concept of traceability. With this scheme, reference laboratories can demonstrate their performance by participation and thereby fulfill one of three criteria required for being listed in the JCTLM database.

The measurement results in RELA shall be based on a high metrological level. Consequently the values of the reported measurands should be expressed in SI-units. The authors feel confident and therefore act on the recommendation of IFCC and IUPAC [17, 18] using the uniform and internationally accepted system of measurement units. The comparability of test results would not be improved, but the metrological aspects of RELA more lightened by the global implementation of SI-units.

It must be stressed that realization of RELA is a dynamic process. Hence, there is always room for discussion, e.g., about the setting of LoE. C-TLM and the organizers are always interested in ways to develop the scheme.

The control samples distributed to participants are of human origin and lyophilized. Such a material meets the requirements for shipment worldwide where ambient temperature may be high, and where customs procedures may delay delivery. The use of such processed material is continuously under discussion. This discussion is always correlated with the key word ‘commutability’ or – probably better to say – ‘non-commutability’.

It has to be stated that in contrast to the evaluation of routine methods this is not an issue for a variety of RMP. CCQM identified procedures as primary methods [19]: e.g., isotope dilution with mass spectrometry, coulometry, and gravimetry. An advantage of these procedures is that it can be assumed that they are independent of matrix effects.

The situation for enzymes is quite different. The IFCC reference measurement procedures for enzymes are described in detail and must be followed strictly. It might be even advantageous that RELA can reveal difficulties such as the sensitivity of creatine kinase to the water temperature during reconstitution of lyophilized material and also to light.

Nevertheless, efforts are required in future to distribute materials of investigation for RELA which can better simulate native human biological material.

So, the potential of using liquid frozen human serum will have to be investigated.

RELA is performed once every year. The identity of each participant is disclosed and the data are publicly available for everyone interested. Identification of accredited laboratories according to ISO 17025 and ISO 15195 as calibration laboratories would provide additional and important information. These data will be added in the near future, not only for discussion of results, but also for potential customers who intend to use a reference measurement service.

Concerning the list of measurands, IFCC is interested in extending the portfolio. Therefore, starting with RELA 2012, the survey includes 25-hydroxyvitamin D3. The organizers are prepared to add further measurands on request.

Corresponding author: Anja Kessler, Reference Laboratory 1, Reference Institute for Bioanalytics, Bonn, Germany

Sincere thanks go to all participants of C-TLM meetings in recent years. They support the process of RELA with their feedback, critical statements and engagement.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

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Received: 2012-6-28
Accepted: 2012-10-22
Published Online: 2013-01-18
Published in Print: 2013-05-01

©2013 by Walter de Gruyter Berlin Boston

Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Editorial
  4. Progress towards standardization: an IFCC Scientific Division Perspective
  5. Review
  6. Quantitative Clinical Chemistry Proteomics (qCCP) using mass spectrometry: general characteristics and application
  7. Mini Reviews
  8. Analytical goals for the determination of HbA2
  9. Glucose meters – fit for clinical purpose
  10. Opinion Papers
  11. Metrological traceability – a concept for standardization in laboratory medicine
  12. Recommendations for clinical laboratory science reports regarding properties, units, and symbols: the NPU format1)
  13. “Good samples make good assays” – the problem of sourcing clinical samples for a standardization project
  14. Defining acceptable limits for the metrological traceability of specific measurands
  15. Original Articles
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  17. Toward standardization of carbohydrate-deficient transferrin (CDT) measurements: III. Performance of native serum and serum spiked with disialotransferrin proves that harmonization of CDT assays is possible
  18. External Quality Assessment Scheme for reference laboratories – review of 8 years’ experience
  19. Utility of a panel of sera for the alignment of test results in the worldwide multicenter study on reference values
  20. Protocol and standard operating procedures for common use in a worldwide multicenter study on reference values
  21. Guidelines and Recommendations
  22. 2013 update on the worldwide standardization of the hemoglobin A1c measurement
  23. General Clinical Chemistry and Laboratory Medicine
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  26. Procalcitonin and mid-regional pro-adrenomedullin test combination in sepsis diagnosis
  27. Cysteinyl leukotrienes in exhaled breath condensate of smoking asthmatics
  28. Helicobacter pylori serology in autoimmune diseases – fact or fiction?
  29. Serum DNase I activity in systemic lupus erythematosus: correlation with immunoserological markers, the disease activity and organ involvement
  30. Antibodies against Nε-homocysteinylated proteins in patients on different methods of renal replacement therapy
  31. Reference Values and Biological Variations
  32. Reference values for urinary neutrophil gelatinase-associated lipocalin (NGAL) in pediatric age measured with a fully automated chemiluminescent platform
  33. High biological variation of serum hyaluronic acid and Hepascore, a biochemical marker model for the prediction of liver fibrosis
  34. Cardiovascular Diseases
  35. Circulating matrix Gla protein: a potential tool to identify minor carotid stenosis with calcification in a risk population
  36. Midregional pro-atrial natriuretic peptide in the general population/Insights from the Gutenberg Health Study
  37. Letters to the Editor
  38. Relationship between Helicobacter pylori infection and autoimmune disorders
  39. Rapid simultaneous genotyping of polymorphisms in ADH1B and ALDH2 using high resolution melting assay
  40. Comparison of biological specimens and DNA collection methods for PCR amplification and microarray analysis
  41. Transferrin/log(ferritin) ratio: a self-fulfilling prophecy when iron deficiency is defined by serum ferritin concentration
  42. Response to: Transferrin/log(ferritin) ratio: a self-fulfilling prophecy when iron deficiency is defined by serum ferritin concentration
  43. Determinants of homocysteine concentrations in mother and neonatal girl pairs
  44. Cysteine analog breaks cryoprecipitate associated with chronic hepatitis C
  45. Cut-off values of serum growth hormone (GH) in pharmacological stimulation tests (PhT) evaluated in short-statured children using a chemiluminescent immunometric assay (ICMA) calibrated with the International Recombinant Human GH Standard 98/574
  46. Normalized MEDx chart as a useful tool for evaluation of analytical quality achievements. A picture is worth a thousand words
  47. Harmonization of immunoassays to the all-procedure trimmed mean – proof of concept by use of data from the insulin standardization project
  48. Congress Abstracts
  49. Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias & International Meeting of Porphyria Patients: Personalized Medicine and Rare Diseases
https://doi.org/10.1515/cclm-2012-0722
Keywords for this article
external quality assessment scheme; reference measurement procedure; traceability

Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Editorial
  4. Progress towards standardization: an IFCC Scientific Division Perspective
  5. Review
  6. Quantitative Clinical Chemistry Proteomics (qCCP) using mass spectrometry: general characteristics and application
  7. Mini Reviews
  8. Analytical goals for the determination of HbA2
  9. Glucose meters – fit for clinical purpose
  10. Opinion Papers
  11. Metrological traceability – a concept for standardization in laboratory medicine
  12. Recommendations for clinical laboratory science reports regarding properties, units, and symbols: the NPU format1)
  13. “Good samples make good assays” – the problem of sourcing clinical samples for a standardization project
  14. Defining acceptable limits for the metrological traceability of specific measurands
  15. Original Articles
  16. A reference system for urinary albumin: current status
  17. Toward standardization of carbohydrate-deficient transferrin (CDT) measurements: III. Performance of native serum and serum spiked with disialotransferrin proves that harmonization of CDT assays is possible
  18. External Quality Assessment Scheme for reference laboratories – review of 8 years’ experience
  19. Utility of a panel of sera for the alignment of test results in the worldwide multicenter study on reference values
  20. Protocol and standard operating procedures for common use in a worldwide multicenter study on reference values
  21. Guidelines and Recommendations
  22. 2013 update on the worldwide standardization of the hemoglobin A1c measurement
  23. General Clinical Chemistry and Laboratory Medicine
  24. Evacuated blood-collection tubes for haematological tests – a quality evaluation prior to their intended use for specimen collection
  25. Refrigeration is not necessary for measurement of uric acid in patients treated with rasburicase
  26. Procalcitonin and mid-regional pro-adrenomedullin test combination in sepsis diagnosis
  27. Cysteinyl leukotrienes in exhaled breath condensate of smoking asthmatics
  28. Helicobacter pylori serology in autoimmune diseases – fact or fiction?
  29. Serum DNase I activity in systemic lupus erythematosus: correlation with immunoserological markers, the disease activity and organ involvement
  30. Antibodies against Nε-homocysteinylated proteins in patients on different methods of renal replacement therapy
  31. Reference Values and Biological Variations
  32. Reference values for urinary neutrophil gelatinase-associated lipocalin (NGAL) in pediatric age measured with a fully automated chemiluminescent platform
  33. High biological variation of serum hyaluronic acid and Hepascore, a biochemical marker model for the prediction of liver fibrosis
  34. Cardiovascular Diseases
  35. Circulating matrix Gla protein: a potential tool to identify minor carotid stenosis with calcification in a risk population
  36. Midregional pro-atrial natriuretic peptide in the general population/Insights from the Gutenberg Health Study
  37. Letters to the Editor
  38. Relationship between Helicobacter pylori infection and autoimmune disorders
  39. Rapid simultaneous genotyping of polymorphisms in ADH1B and ALDH2 using high resolution melting assay
  40. Comparison of biological specimens and DNA collection methods for PCR amplification and microarray analysis
  41. Transferrin/log(ferritin) ratio: a self-fulfilling prophecy when iron deficiency is defined by serum ferritin concentration
  42. Response to: Transferrin/log(ferritin) ratio: a self-fulfilling prophecy when iron deficiency is defined by serum ferritin concentration
  43. Determinants of homocysteine concentrations in mother and neonatal girl pairs
  44. Cysteine analog breaks cryoprecipitate associated with chronic hepatitis C
  45. Cut-off values of serum growth hormone (GH) in pharmacological stimulation tests (PhT) evaluated in short-statured children using a chemiluminescent immunometric assay (ICMA) calibrated with the International Recombinant Human GH Standard 98/574
  46. Normalized MEDx chart as a useful tool for evaluation of analytical quality achievements. A picture is worth a thousand words
  47. Harmonization of immunoassays to the all-procedure trimmed mean – proof of concept by use of data from the insulin standardization project
  48. Congress Abstracts
  49. Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias & International Meeting of Porphyria Patients: Personalized Medicine and Rare Diseases
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