Strategies to set global analytical quality specifications in laboratory medicine: 10 years on from the Stockholm consensus conference

The setting of analytical quality specifications in laboratory medicine has attracted attention for many years. Over time, many strategies were advocated and all had advantages and disadvantages. In the final decade of the last millennium, considerable confusion existed on how to define analytical quality specifications correctly and how to apply them in everyday practice. This led to wide professional interest. In 1999, a consensus conference sponsored by IUPAC, IFCC and WHO was held in Stockholm on “Strategies to Set Global Analytical Quality Specifications in Laboratory Medicine”. The consensus set useful and well-documented strategies for the setting of analytical quality specifications into a hierarchy with the best strategy at the highest level, namely, (1) Evaluation of the effect of analytical performance on clinical outcomes in specific clinical situations, (2) Evaluation of the effect of analytical performance on clinical decisions in general, (3) Published professional recommendations, (4) Performance goals set by regulatory bodies and EQAS organisers, and (5) Goals based on the current state of the art. Much success has been achieved since the promulgation of the statement with the approach being adopted by many in laboratory medicine for a very wide variety of purposes, particularly in quality management. However, there is a requirement for additional investigation of, inter alia, quality specifications for examinations done on measurements performed on ordinal and nominal scales, pre-analytical factors and matrix effects, examinations done as POCT, target values of control materials, and ways in which analytical quality specifications can be used both to set what is the optimum performance and as a tool for assessment of everyday practice.     

Remembering the Stockholm Consensus

Last year marked the tenth anniversary of the conference Strategies to Set Global Quality Specifications in Laboratory Medicine, which was held in Stockholm. The main outcome of this conference was a hierarchy of models to set metrological requirements, commonly known as the Stockholm Consensus. Belief in the appropriateness and scientific rigour of this Consensus has since been disseminated around the world. The Stockholm Consensus has made the biological variation model the model that is most commonly used to set metrological requirements. However, this model is not objective, because it is based on the selection of the one of three multiplication factors that reflects the mean biological variation. In addition to this lack of objectivity and other weaknesses of the biological variation model, the so-called Stockholm Consensus was not a true consensus process. Since our knowledge of this field continues to grow, the setting of metrological requirements should be a matter of true consensus based on the state of the art, rather than a “pseudo-objective” process. Metrological requirements should ensure that clinical laboratories do not produce measurement results that are less precise than their measuring systems allow.     

Keeping the spotlight on quality from a distance

 Maintaining the quality of testing in remote locations can be demanding of laboratory resources in terms of daily visits to instruments and providing support outside of normal working hours. Recently technology and software solutions have appeared to reduce this burden for laboratory scientists dramatically. The AVL Auto QC unit, in conjunction with OMNILink software, allow laboratory staff to perform many quality control and maintenance procedures on instruments in wards and medical units from a PC in the central laboratory. Assessment of this technology and software in the Special Baby Care Unit at Bradford Royal Infirmary has demonstrated many benefits including reduction in ward visits, better support out of hours, regular quality control checks, and improved analytical quality. Received: 15 April 2000 · Accepted: 15 April 2000     

Telematics applications in a laboratory cluster

 The laboratories of six hospitals in the Canton of Wallis in Switzerland have been connected to one central laboratory, using the same database, the same software applications for the laboratory, pathology and pharmacy, and the same office and administration software. Some instruments in "Point of Care" sites are online for result transmission and for telemaintenance. The physicians may order drugs, material for sampling, analyses for specified patients and may consult knowledge bases, the patient data base, results and reports in different formats (ASCII, HTML, PDF, JPG, GIF, ...) using browsers like Netscape or MS-Explorer. To guarantee privacy, the access is restricted and protected by user-name, password and firewall. This report describes conditions for a successful introduction and usage of quality management through laboratory telematics. Received: 15 April 2000 · Accepted: 15 April 2000     

I International Conference on the Low-Temperature Chemistry

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I International Conference on the Low-Temperature Chemistry     

HTMC XII in Vienna

The International IUPAC Conference on High Temperature Materials Chemistry HTMC XII in Vienna/Austria from September 17 to 22, 2006, was the twelfth conference in a series of triennial meetings, with the previous two held in 2000 in Juelich (Germany), and in 2003 in Tokyo (Japan).     

The EC4 European Register for Clinical Chemists in relation to quality aspects

 The European Register for Clinical Chemists is founded and guarded by the European Communities Confederation of Clinical Chemistry (EC4). This register fits the current mind set of harmonization and globalization of occupations within the European Community. But in addition it enables and serves the continuing quest for quality assessment and improvement within the field of laboratory medicine. The content and position of clinical chemists in the European Union is described and the European Register outlined. Received: 10 July 2000 / Accepted: 20 July 2000     

The quest for comparability: Calibration 2000

 Most efforts in quality control have been focussed on the reduction of intralaboratory variation and the assessment of interlaboratory variation. Over the last few years, the importance of bias in interlaboratory variation and intralaboratory shifts has become clear. Small shifts can sometimes have a large impact on the number of treated patients, particularly in assays where cut off values are used. For example in cholesterol, HDL-cholesterol, HbA1c and TSH assays. There is an obvious need for adequate calibration material. However, the process of development of international primary reference materials and reference methods takes time, and even if reference materials exist and are used by in vitro diagnostics manufacturers, there still remains significant and clinically relevant interlaboratory variance and intralaboratory shifts, as is seen, e.g. in protein chemistry. The harmonization of inter laboratory and intralaboratory results needs an impulse from professional organizations to convince individual laboratories of the importance and significance of bias. This applies to all subdisciplines of laboratory medicine. On the occasion of the 25th anniversary of the Foundation for External Quality Assessment (SKZL), a large interdisciplinary harmonization project called Calibration 2000 was launched in The Netherlands The strategy and first results are reported in this paper. The project aims at harmonization of laboratory data of several disciplines, using secondary calibration materials, leading to common reference ranges throughout The Netherlands. Received: 15 April 2000 · Accepted: 15 April 2000     

Reference intervals of serum folate and vitamin B12 developed from data of healthy subjects

 In this study the reference intervals for folate and vitamin B₁₂ were estimated according to the National Committee for Clinical Laboratory Standards Approved Guideline C28-A and International Federation of Clinical Chemistry recommendations. The study included 155 women and 124 men between ages 18–40. The health status was confirmed by history, physical examination and a questionnaire. The central 95% reference intervals of serum folate and vitamin B12 for women, determined non-parametrically, were found to be 3.9–18.1 ng/ml and 101–666.7 pg/ml, respectively. The reference values of serum folate and vitamin B12 for men were also found to be 2,5–17.6 ng/ml and 100–699.57 pg/ml, respectively. We did not observe subclass differences between females and males. Received: 15 April 2000 · Accepted: 15 April 2000     

Quality assurance in immunogenetics and histocompatibility: experience with EFI Accreditation

 The European Federation for Immunogenetics (EFI) has its own standards for histocompatibility testing. Compared with EN 45001 and ISO Standards, EFI Standards are more detailed, actually stating "what to do" in the laboratory. The decision of Eurotransplant that all its organ transplantation programmes must be EFI-accredited by the year 2000, illustrates the importance of the these standards. It took us 11 months to prepare the EFI questionnaire, describing the main features of our laboratory and how they complied with EFI Standards. After approval of this file, inspection was performed by a team of two peers who routinely worked in an EFI-accredited tissue typing laboratory. The pre-analytical, analytical and post-analytical phases were inspected during a one day visit. Furthermore, a checklist was reviewed against the laboratory's documentation system. Within 1 month of reception of the inspection report, we were expected to send a reply listing the corrective actions taken. Upon acknowledgement of the latter, EFI Accreditation was granted, for 1 year. We feel that detailed standards, specifically designed for a certain type of laboratory, offer many advantages. Received: 15 April 2000 · Accepted: 15 April 2000     

Total quality management in hematology

 Healthcare is changing and clinical laboratory testing must change with it. In no discipline is this change more profound than in hematology. The principles of total quality management (TQM) including continuous quality improvement, reengineering and strategic planning can facilitate these changes. In the past, hematology has often been exlcuded from these processes due to its many manual procedures and the degree of expertise and skill needed to perform the testing. As automated technology continues to evolve, hematology testing, like other testing, will become integrated into the core, clinical laboratory. We suggest TQM can, and should, guide the way. Received: 15 April 2000 · Accepted: 19 April 2000     

The VIIth International Conference on the Organometallic and Coordination Chemistry of Germanium,Tin, and Lead

Information Congresses, Conferences, Symposia, Meetings, and Seminars held with the Participation of the Russian Academy of Sciences

The VIIth International Conference on the Organometallic and Coordination Chemistry of Germanium, Tin, and Lead     

30. Welttreffen der Koordinationschemiker

Fazit der Standortbestimmung der 30. International Conference on Coordination Chemistry (ICCC) im heißen Kyoto Juli '94: Besonders stark notiert sind „Chemistry for Health”︁, Koordinationschemie der Hauptgruppenelemente und Vorstöße in topologisches Neuland. Viel Neues gab es auch bei den Klassikern Homogenkatalyse, Organometallchemie, Synthese, Struktur und Theorie.     

Detection and Quantification Capabilities and the Evaluation of Low-Level Data: Some International Perspectives and Continuing Challenges

The minimum amounts or concentrations of an analyte that may be detected or quantified by a specific measurement process (MP) represent fundamental performance characteristics that are vital for planning experiments and designing MPs to meet external specifications. Following many years of conceptual and terminological disarray regarding detection and quantification limits, the International Union of Pure and Applied Chemistry (IUPAC, 1995) and the International Organization for Standardization (ISO, 1997) developed a harmonized position and documents that provide a basis for international consensus on this topic. During the past year, the International Atomic Energy Agency (IAEA) has developed a TECDOC on Quantifying Uncertainty in Nuclear Analytical Measurements that treats "Uncertainty in Measurements Close to Detection Limits" from the perspective of the IUPAC and ISO recommendations. The first part of this article serves as a review of these international developments during the last quinquennium of the twentieth century. Despite the achievement of international consensus on these contentious matters, many challenges remain. One quickly discovers this in the practical world of high stakes, ultra-trace analysis, where complications are introduced by the nature and distribution of the blank, the variance function ( vs. concentration), non-linear models, and hidden algorithms and data evaluation/reporting schemes. Some of these issues are illustrated through a multidisciplinary case study of fossil and biomass burning aerosol at extremely low levels in the polar atmosphere and cryosphere, and by biased reporting practices for "non-detects."     

Quality specifications in laboratory medicine – current consensus views

Every analytical method used in laboratory medicine can be fully described in terms of its performance characteristics. Ideally, quality specifications should be available for all of these, particularly precision and bias. Specifications for these can be set using a variety of strategies. Consideration of the clinical settings of monitoring individual patients and diagnosis using reference intervals shows that generally applicable quality specifications can be based on the components of biological variation, namely, within-subject [CV_I] and between-subject [CV_G] variation. Current consensus is that precision should be <1/2CV_I and bias should be <1/4[CV_I ²+CV_G ²]^1/2. This strategy has advantages in that data on components of biological variation are easily available on more than 180 quantities. Dissemination of information on application of objective quality specifications needs attention from those involved in publication, manufacturers and organisers of external quality assessment schemes.     

Estimation of the uncertainty of CRMs in accordance with GUM: Application to the certification of four enzyme CRMs

Uncertainties of four enzyme-CRMs that have recently been certified in a co-operation between the IRMM and the International Federation for Clinical Chemistry were estimated. Estimation was based on the sum of the uncertainties of characterization, homogeneity and stability. Data from the certification collaborative study were used to estimate laboratory uncertainties, which form the basis for the uncertainty of characterization. Estimations for the uncertainty of homogeneity were derived from classical homogeneity studies. The estimations of uncertainty of stability caused the most difficulties. Realistic uncertainties fitting the needs of customers while being derived from measurement data based on theoretical considerations were obtained. Received: 11 May 2000 / Revised: 21 June 2000 / Accepted: 27 June 2000     

Metrology in laboratory medicine – Reference measurement systems

 The medical laboratory must provide results of measurements that are comparable over space and time in order to aid medical diagnosis and therapy. Thus, metrological traceability, preferably to the SI, is necessary. The task is formidable due to the many disciplines involved, the high production rate, short request-to-report time, small sample volumes, microheterogeneity of many analytes, and complex matrices. The prerequisite reference measurement systems include definition of measurand, unit of measurement (when applicable), consecutive levels of measurement procedures and calibrators in a calibration hierarchy, international organizations, reference measurement laboratories, dedicated manufacturers, written standards and guides for the medical laboratory, production of reference materials, internal and external quality control schemes, and increasingly accreditation. The present availability of reference measurement procedures and primary calibrators is shown to be insufficient to obtain international comparability of all types of quantity in laboratory medicine. Received: 19 April 2000 / Accepted: 3 July 2000     

13. International Conference on Chemical Education

In zweijährigem Rhythmus findet die International Conference on Chemical Education (ICCE) statt. Ende 1994 trafen sich über 600 Schul- und Hochschullehrer sowie am naturwissenschaftlichen Unterricht interessierte Wissenschaftler aus über 60 Ländern auf dem Metropolitan Campus der Interamerican University of Puerto Rico in San Juan unter dem Motto “Chemistry: The Key to The Future”.     

Rohstoff Bildung: Chemie in Jordanien

Internationale Kooperationen auch mit deutschen Chemikern legen die Grundlage für eine fundierte Chemieausbildung in Jordanien. Eindrücke von der Third Jordanian International Conference of Chemistry.     

Improvements in performance in medical diagnostics tests documented by interlaboratory comparison programs

There is evidence to support the notion that interlaboratory comparisons (ILCs) are an effective tool for laboratory improvement. However, despite widespread experience and anecdotal evidence of improvements there are few published studies demonstrating any benefits from ILCs– in any field of testing. Published demonstrations of benefits can help justify the growing use of ILCs. ILCs and proficiency testing have been common for many years in medical laboratories; there has been open information on the results of ILCs, and there has been standardization of results from thousands of laboratories. These studies show general improvement over time in several areas of testing in different countries. Many articles cite specific reasons for the improvements, either proven or supposed. An early version of this paper was presented at the International Laboratory Accreditation Cooperation Conference ”ILAC 2000” in Washington D.C., on 31October, 2000. Received: 10 February 2001 Accepted: 21 January 2002