临床检验前阶段室间质量评价方案的设计

在检验医学领域中,有很多研究已描述检验全过程不同阶段出现的最频繁的差错,且这些差错的很大部分都出现在检验前阶段。检验中阶段的误差登记然后反馈给参加者的方案已经由室间质评（External Quality Assessment,EQA）组织在大多数国家进行了数十年。但是迄今为止,只有很少的组织专注于检验前阶段,而且大多数的EQA组织并不提供检验前EQA方案（External Quality Assessment Schemes,EQAS）。执行和标准化检验前EQAS是比较困难的,认可机构也并没有对实验室参加这类方案提出要求。然而,一些正在进行的检验前阶段EQA计划是存在的,使用的方法可以分为三种类型：收集实验室检验前程序的信息、发放真实样品来收集可能影响测量程序的干扰因素、或者登记真实的实验室差错并将这些内容关联到质量指标。这三个类型有不同的侧重点和不同的实施挑战,这三者的结合可能是检出和监视出现在检验前阶段的广泛差错所必须的。     

Quality of plasma cholesterol measurements in primary care.

Three surveys were made of the quality of plasma cholesterol measurements performed with a commercial desktop analyser (BCL Reflotron) in primary care. Each survey included three specimens, and results were received from 37, 61, and 69 participants. Although many participants obtained satisfactory results, 8.6% of the results differed by 1.0 mmol/l or more from the target values, and the overall between instrument dispersion of results was 1.3 times that between hospital laboratories. It was found that common sources of error were poor technique and the use of outdated reagent strips. Users of such instruments outside the laboratory need help and advice with training, and guidelines for this are provided. The main recommendations are that users should establish contact with a local clinical chemistry laboratory for training and support and should participate in external quality assessment schemes.     

Verification of quantitative analytical methods in medical laboratories

BackgroundGlobally, all medical laboratories seeking accreditation should meet international quality standards to perform certain specific tests. Quality management program provides disciplines targeted to ensure that quality standards have been implemented by a laboratory in order to generate correct results. The hallmark of the accreditation process is method verification and quality assurance. Before introducing a new method in your laboratory, it is important to assess certain performance characteristics that reflect the concept of method verification.MethodsIn this review, we illustrated how to verify the performance characteristics of a new method according to the recent guidelines. It includes an assessment of precision, trueness, analytical sensitivity, detection limits, analytical specificity, interference, measuring range, linearity, and measurement uncertainty.ConclusionsAlthough the presence of several updated guidelines used to determine the performance characteristics of new methods in clinical chemistry laboratories, the real practice raised several concerns with the application of these guidelines which in need for further consideration in the upcoming updates of these guidelines.     

Monitoring standards for molecular genetic testing in the United Kingdom, the Netherlands, and Ireland

Molecular genetic techniques have entered many areas of clinical practice. Public expectations from this technology are understandably high. To maintain confidence in this technology, laboratories must implement the highest standards of quality assurance (QA). External quality assessment (EQA) is recognized as an essential component of QA. The United Kingdom National External Quality Assessment Service (UKNEQAS) for Molecular Genetics, first set up in 1991, is currently the longest provider of EQA to molecular genetic testing laboratories in the UK, The Netherlands, and Ireland. Errors in the scheme are sporadic events. However, evidence from this and other EQA schemes suggests that a residual error rate persists, which should be taken into account in clinical practice. This EQA scheme has evolved from the respective scientific bodies of the constituent countries and retains a strong emphasis on collective peer review. It is essential that the steps taken to ensure quality in this rapidly expanding field are clear and transparent to participants and public alike. We describe the procedures developed and the governance imposed to monitor and improve analytical and reporting standards in participant laboratories and we compare our experiences with those of equivalent EQA services in the United States.     

Requirements for reference (calibration) laboratories in laboratory medicine

In addition to reference measurement procedures and reference materials, reference or calibration laboratories play an integral role in the implementation of measurement traceability in routine laboratories. They provide results of measurements using higher-order methods, e.g. isotope dilution mass spectrometry and may assign values to materials to be used for external quality assessment programs and to secondary reference materials. The requirements for listing of laboratories that provide reference measurement services include a statement of the metrological level or principle of measurement, accreditation as a calibration laboratory according to ISO 15195 and the participation in a proficiency testing system (regular inter-laboratory comparisons) for reference laboratories. Ring trials are currently conducted for thirty well-defined measurands and the results are made available to all laboratories. Through the use of reference laboratory services that are listed by the Joint Committee for Traceability in Laboratory Medicine there is the opportunity to further promote traceability and standardisation of laboratory measurements.     

Assessing accuracy and precision for field and laboratory data: a perspective in ecosystem restoration

Unlike most laboratory studies, rigorous quality assurance/quality control (QA/QC) procedures may be lacking in ecosystem restoration (“ecorestoration”) projects, despite legislative mandates in the United States. This is due, in part, to ecorestoration specialists making the false assumption that some types of data (e.g. discrete variables such as species identification and abundance classes) are not subject to evaluations of data quality. Moreover, emergent behavior manifested by complex, adapting, and nonlinear organizations responsible for monitoring the success of ecorestoration projects tend to unconsciously minimize disorder, QA/QC being an activity perceived as creating disorder. We discuss similarities and differences in assessing precision and accuracy for field and laboratory data. Although the concepts for assessing precision and accuracy of ecorestoration field data are conceptually the same as laboratory data, the manner in which these data quality attributes are assessed is different. From a sample analysis perspective, a field crew is comparable to a laboratory instrument that requires regular “recalibration,” with results obtained by experts at the same plot treated as laboratory calibration standards. Unlike laboratory standards and reference materials, the “true” value for many field variables is commonly unknown. In the laboratory, specific QA/QC samples assess error for each aspect of the measurement process, whereas field revisits assess precision and accuracy of the entire data collection process following initial calibration. Rigorous QA/QC data in an ecorestoration project are essential for evaluating the success of a project, and they provide the only objective “legacy” of the dataset for potential legal challenges and future uses.     

Frequent major errors in antimicrobial susceptibility testing of bacterial strains distributed under the Deutsches Krebsforschungszentrum Quality Assurance Program

The Quality Assurance Program (QAP) of the Deutsches Krebsforschungszentrum (DKFZ) was a proficiency testing system developed to service the laboratory animal discipline. The QAP comprised the distribution of bacterial strains from various species of animals for identification to species level and antibiotic susceptibility testing (AST). Identification capabilities were below acceptable standards. This study evaluated AST results using the DKFZ compilations of test results for all bacterial strains showing the number of participants reporting the strain as resistant (R), sensitive (S) or intermediate susceptible (I) to each antibiotic substance used. Due to lack of information about methods used, it was assumed that what the majority of the participants reported (R or S) was the correct test result and that an opposite result was a major error (ME). MEs occurred in 1375 of 14,258 (9.7%) of test results and ME% ranged from 0% to 23.2% per bacterial group-agent group combination. Considerable variation in MEs was found within groups of bacteria and within groups of agents. In addition to poor performance in proper species classification, the quality of AST in laboratory animal diagnostic laboratories seems far below standards considered acceptable in human diagnostic microbiology.     

6σ 质量管理方法在临床化学检测性能评价中的应用

目的:应用六西格玛(6σ)质量管理方法分析临床生化检验项目质量控制数据,评价其分析性能,设计生化检验项目的质量控制方法并指导其质量改进。方法:收集2010年度临床生化检验项目室内质量控制及室间质量评价的数据,按照美国临床实验室改进修正法案允许总误差(TEa)标准,采用公式值=[TEa%-偏倚(bias%)]/变异系数(CV%),计算检验项目的σ值,绘制标准化6σ性能决定图,评价检验项目分析性能,设计质量控制方案,计算检验项目的质量目标指(QGI),查找导致性能不佳的主要原因,提出优先改进方法。结果:临床生化检验项目中,常规生化和干式生化的检验项目达到6西格玛水平分别占66.6%和58.4%,达到5～6西格玛水平分别占4.8%和8.3%,达到4～5西格玛水平分别占4.8%和8.3%,4.达到3～4西格玛水平分别占4.8%和16.7%,在3西格玛水平以下分别占19%和8.3%,全部检验项目的平均σ值分别为9.33和6.95。在12个6σ值<6的检验项目中有50%要优先改进精密度,25%需要优先改进准确度,其余则两者都要改进。结论:6σ质量管理方法可以有效地应用于临床化学检测性能评价,设计个性化的质量控制方案可更有效地控制质量,有助于不断提高临床实验室生化检验项目质量水平。     

Quality standards in proteomics research facilities: Common standards and quality procedures are essential for proteomics facilities and their users

Proteomics research infrastructures and core facilities within the Core for Life alliance advocate for community policies for quality control to ensure high standards in proteomics services.

Core facilities and research infrastructures have become an essential part of the scientific ecosystem. In the field of proteomics, national and international networks and research platforms have been established during the past decade that are supposed to set standards for high‐quality services, promote an exchange of professional information, and enable access to cutting‐edge, specialized proteomics technologies. Either centralized or distributed, these national and international proteomics infrastructures and technology platforms are generating massive amounts of data for the research community, and support a broad range of translational, computational and multi‐omics initiatives and basic research projects.By delegating part of their work to these services, researchers expect that the core facility adjusts their analytical protocols appropriately for their project to acquire data conforming best research practice of the scientific community. The implementation of quality assessment measures and commonly accepted quality controls in data generation is therefore crucially important for proteomics research infrastructures and the scientists who rely on them.However, current quality control and quality assessment procedures in proteomics core facilities and research infrastructures are a motley collection of protocols, standards, reference compounds and software tools. Proteomics relies on a customized multi‐step workflow typically consisting of sample preparation, data acquisition and data processing, and the implementation of each step differs among facilities. For example, sample preparation involves enzymatic digestion of the proteins, which can be performed in‐solution, in‐gel, or on‐beads, with often different proteolytic enzymes, chemicals, and conditions among laboratories. Data acquisition protocols are often customized to the particular instrument set up, and the acquired spectra and chromatograms are processed by different software tools provided by equipment vendors, third parties or developed in‐house.

…current quality control and quality assessment procedures in proteomics core facilities and research infrastructures are a motley collection of protocols, standards, reference compounds and software tools.

Moreover, core facilities implement their own guidelines to monitor the performance and quality of the entire workflow, typically utilizing different commercially available standards such as pre‐digested cell lysates, recombinant proteins, protein mixtures, or isotopically labeled peptides. Currently, there is no clear consensus on if, when and how to perform quality control checks. There is even less quality control in walk‐in facilities, where the staff is only responsible for correct usage of the instruments and users select and execute the analytical workflow themselves. It is not surprising therefore that instrument stability and robustness of the applied analytical approach are often unclear, which compromises analytical rigor.     

Analytical quality--what should we be aiming for?

ISO 15189 5.5.1 "The laboratory shall use examination procedures, ... which meet the needs of the users of laboratory services and are appropriate for the examinations. Requirements for analytical quality include: understanding the analytical goal; seeking an assay that fulfills those goals; establishing your own performance with that assay; setting warning and action limits for your assay; applying quality control tools to every important step.     

Reference materials and commutability

Maintaining accurate laboratory measurements over time is crucial for assuring appropriate patient care and disease management. Accurate results over time and location are achieved by standardising measurements and establishing traceability to a reference system. Reference materials are key components of such reference systems and for establishing traceability. Commutability of reference materials is a critical property to ensure they are fit for use.Commutability is defined as the equivalence of the mathematical relationships between the results of different measurement procedures for a reference material and for representative samples from healthy and diseased individuals. This material characteristic is of special importance for measurement procedures that are optimised for measuring analytes directly in patient samples. The commutability of a reference material is measurement procedure specific and its assessment requires special experimental designs.This review explains the importance of commutability and summarises different experimental approaches described in the literature that have been used to assess the commutability of reference materials in clinical chemistry.     

An international comparability study on quantification of total methyl cytosine content

Various methods have been developed for quantitative analysis of DNA methylation. However, there is currently no reference analysis system regarding DNA methylation with which other analytical approaches can be compared and evaluated. A standard measurement system that includes reference methods and reference materials may improve comparability and credibility of data obtained from different analytical environments. In an effort to establish a standard system for measurement of DNA methylation, the Korea Research Institute of Standards and Science (KRISS) coordinated an international comparison study among different national metrology institutes. An initial stage of the study involved an intercomparison regarding quantitative measurement of total methyl cytosine contents in artificially constructed DNA samples. The measurement principle involved measurement of dNMP contents following enzymatic hydrolysis of DNA samples. Results of the study showed good comparability among four of five participants and close agreement with reference values assigned by the coordinating laboratory. Conflicting data from one participant may have resulted from incomplete hydrolysis of samples due to use of insufficient amounts of enzymes. These results indicate that comparable and accurate results can be obtained from different measurement environments if digestion conditions are controlled appropriately and valid calibration systems are employed.     

External quality assessment in water microbiology: statistical analysis of performance

H.E. TILLETT, N.F. LIGHTFOOT AND S. EATON. 1993. A UK-based scheme of water microbiology assessment requires participants to record counts of relevant organisms. Not every sample will contain the target number of organisms because of natural variation and therefore a range of results is acceptable. Results which are tail-end (i.e. at the extreme low or high end of this range) could occasionally be reported by any individual laboratory by chance. Several tail-end results might imply a laboratory problem. Statistical assessment is done in two stages. A non-parametric test of the distribution of tail-end counts amongst laboratories is performed (Cochran's Q) and, if they are not random, then observed and expected frequencies of tail-end counts are compared to identify participants who may have reported excessive numbers of low or high results.
Analyses so far have shown that laboratories find high counts no more frequently than would be expected by chance, but that significant clusters of low counts can be detected among participants. These findings have been observed both in short-term and in long-term assessments, thus allowing detection of new episodes of poor performance and intermittent problems.
The analysis relies on an objective definition of tail-end results. Working definitions are presented which should identify poor performance in terms of microbiological significance, and which allow fair comparison between membrane-filtration and multiple-tube techniques. Smaller differences between laboratories, which may be statistically significant, will not be detected. Different definitions of poor performance could be incorporated into future assessments.     

The Yorkshire slide exchange external quality assessment (EQA) scheme

A slide circulation scheme measuring cervical screening performance of individual cytologists in 15 laboratories in Yorkshire Regional Health Authority is described. The advantages and disadvantages are compared with the current National Proficiency Testing (NPT) scheme. The results indicate that a slide circulation scheme can be successfully used in cervical cytology external quality assessment (EQA). Levels of participation are better than those currently achieved by regional variations of the NPT scheme, and the use of laboratory consensus in the selection of scoring slides appears to be no less valid than the use of a pre‐selected slide pool assembled by an expert panel. The volume of data accumulated in one round is considerably greater than that achieved by proficiency testing and the educational value is regarded as high. However, the scheme is very time consuming for participants and consequently expensive for laboratories. The lack of external supervision increases the risk of unfair practices within individual laboratories. Because of these problems, Yorkshire has now switched to an NPT scheme.     

Impact of standardization on clinical cell analysis by flow cytometry

The evolution of flow cytometry from a research tool to a pivotal technology for clinical diagnostic purposes has required significant efforts to standardize methods. The great advantage of flow cytometry is that it's applications are highly amenable to standardization. Here, we review the efforts that have been made for flow cytometric applications in four major fields of clinical cell analysis: CD4+ T-cell enumeration, CD34+ hematopoietic stem and progenitor cell enumeration, screening for the HLA-B27 antigen and leukemia/lymphoma immunophenotyping. These standardization efforts have been parallelled by the establishment of external quality assessment (EQA) schemes in many countries worldwide. The goal of these EQA exercises has been primarily educa-tional, but their results will increasingly serve as a basis for laboratory accreditation. This important development requires that the EQA schemes, in particular the quality of the distributed samples and the procedures for evaluating the results, meet the highest standards.     

1997 ESACP consensus report on diagnostic DNA image cytometry. Part I: basic considerations and recommendations for preparation, measurement and interpretation. European Society for Analytical Cellular Pathology.

A task force of invited experts in the field of diagnostic DNA image cytometry, especially consisting of participants from the PRESS (Prototype Reference Standard Slides) and EUROPATH (European Pathology Assisted by Telematics for Healthcare) projects, but open to any other scientist or physician revealing experience in that new diagnostic procedure (names are given in the Annex A) agreed upon the following updated consensus report during the 5th International Congress of the ESACP 1997 in Oslo. This report is based on the preceeding one [9] and on results of the above mentioned European research projects. It deals with the following items: Biological background and aims of DNA image cytometry, Principles of the method, Basic performance standards, Diagnostic interpretation of DNA measurements, Recommendations for practical use.     

Guidelines and considerations for the use of system suitability and quality control samples in mass spectrometry assays applied in untargeted clinical metabolomic studies

Background

Quality assurance (QA) and quality control (QC) are two quality management processes that are integral to the success of metabolomics including their application for the acquisition of high quality data in any high-throughput analytical chemistry laboratory. QA defines all the planned and systematic activities implemented before samples are collected, to provide confidence that a subsequent analytical process will fulfil predetermined requirements for quality. QC can be defined as the operational techniques and activities used to measure and report these quality requirements after data acquisition.

Aim of review

This tutorial review will guide the reader through the use of system suitability and QC samples, why these samples should be applied and how the quality of data can be reported.

Key scientific concepts of review

System suitability samples are applied to assess the operation and lack of contamination of the analytical platform prior to sample analysis. Isotopically-labelled internal standards are applied to assess system stability for each sample analysed. Pooled QC samples are applied to condition the analytical platform, perform intra-study reproducibility measurements (QC) and to correct mathematically for systematic errors. Standard reference materials and long-term reference QC samples are applied for inter-study and inter-laboratory assessment of data.

     

Analysis of heterocyclic amines in food products: interlaboratory studies

A feasibility study and two interlaboratory exercises on the determination of selected heterocyclic amines (HAs) in beef extract, organised in the framework of a European project, are presented. The aim of these exercises was to improve the quality of the laboratories and to evaluate the performance of a standardised analytical method and also the methods currently used by each of the participants for the analysis of these compounds. Three lyophilised portions of a commercial beef material previously spiked with HAs at different concentration levels ranging from 10 to 75 ng g(-1) were used as laboratory reference materials (lot A, B and C). Firstly, a feasibility study was carried out using a test standard solution and the beef extract (lot A), which contained only five HAs. Then, two interlaboratory exercises were carried out using the laboratory reference materials lot B and lot C, containing 10 selected HAs at two different concentration levels, 75 and 10 ng/g, respectively. The results obtained by all participant laboratories using the proposed method showed satisfactory agreement and the CV(%) between-laboratories obtained were from 8.3 to 24.1% for lot B and from 8.7 to 44.5% for lot C. The standardised method evaluated in these collaborative studies is therefore proposed for the analysis of HAs in food material. Moreover, LC-MS is recommended as the most suitable technique for the analysis of a large number of HAs in food samples.     

Performance evaluation of an analytical laboratory the laboratory product model

Background, Intention, Goal and Scope  The analytical laboratory is traditionally considered to be a service provider. This has resulted in laboratory environmental management being considered mostly from a pollution prevention and waste minimization perspective. There is a recognized need to view environmental performance of a laboratory service provider from a broader perspective. This broader perspective is inclusive of sampling, analysis and the potential for impacts to arise from the use of output information products. A generic methodology for the measurement and benchmarking of the overall environmental performance of an analytical laboratory and its outputs using the Laboratory Product Model (LPM) is described. Environmental performance indicators, relating to inputs and processing are proposed. Objectives  The project seeks to broaden the focus of environmental performance away from the individual analytical unit processes to a more encompassing ‘cradle-to-grave’ approach incorporating sample collection and results reporting and use. To support this approach, a functional unit of output for a laboratory has to be defined. Methods  A life cycle assessment approach, incorporating life cycle inventory considerations, is applied within the LPM conceptual framework. Results and Discussion  This approach facilitates a shift in thinking from laboratory service to the life cycle of laboratory product inputs and outputs. It enables LCA methodologies to be applied to environmental performance through the application of the LPM. The definition of a laboratory product output facilitates benchmarking and comparison of laboratories. Conclusions  The LPM approach assigns a critical role to the laboratory for the sustainability of the laboratory operations from sample collection, through analysis to the use of its product outputs. Recommendations and Outlook  The application of the LPM offers a top down approach for the evaluation of the environmental performance of an analytical laboratory. It is expected to provide a useful tool for assessing and benchmarking the environmental performance of analytical laboratories.