A quality systems approach for identifying and controlling sources of error with point of care testing devices

Historically, due to the size and nature of the instrumentation, highly skilled laboratory professionals performed clinical testing in centralized laboratories. Today’s clinicians demand realtime test data at the point of care. This has led to a new generation of compact, portable instruments permitting ”laboratory” testing to be performed at or near the patient’s bedside by nonlaboratory workers who are unfamiliar with testing practices. Poorly controlled testing processes leading to poor quality test results are an insidious problem facing point of care testing today. Manufacturers are addressing this issue through instrument design. Providers of clinical test results, regardless of location, working with manufacturers and regulators must create and manage complete test systems that eliminate or minimize sources of error. The National Committee for Clinical Laboratory Standards (NCCLS) in its EP18 guideline, ”Quality management for unit-use testing,” has developed a quality management system approach specifically for test devices used for point of care testing (POCT). Simply stated, EP18 utilizes a ”sources of error” matrix to identify and address potential errors that can impact the test result. The key is the quality systems approach where all stakeholders – professionals, manufacturers and regulators – collaboratively seek ways to manage errors and ensure quality. We illustrate the use of one quality systems approach, EP18, as a means to advance the quality of test results at point of care. Received: 26 June, 2002 Accepted: 17 July 2002 Presented at the European Conference on Quality in the Spotlight in Medical Laboratories, 7–9 October 2001, Antwerp, Belgium Abbreviations NCCLS National Committee for Clinical Laboratory Standards (formerly) · POCT point of care testing · QC quality control · HACCP hazard analysis critical control points · CLIA clinical laboratory improvement amendments (of 1988) Correspondence to S. S. Ehrmeyer     

Urine dry reagent strip “error” rates using different reading methods

 The need for “quality” in near patient testing (NPT) has been acknowledged since the mid 1980s. The commonest biochemical NPT device is the dry reagent strip or “dipstick” for urinalysis. Dipsticks may be read in three ways, against the color chart printed along the side of the bottle, using a benchreader (the color chart printed on a flat card) or using an electronic reader. This report uses the results of a urinalysis quality assurance (QA) program, over 1998, to evaluate the “error” rates which occur using the three different reading methods. The QA samples are buffered aqueous solutions which are “spiked” to give concentrations midway between two color blocks for each analyte. Results are scored as ±1 if a color block adjacent to the target value, ±2 for results two color blocks (defined as “error”) and ±3 for results three color blocks (defined as “gross error”) from the target value. Analysis of the results show that the error rates are similar reading visually by either method, but greatly reduced when read electronically. Some persisting errors when using the electronic reader are explained by observation studies. The study highlights the value of a urinalysis QA program for NPT urinalysis in understanding the error rates of this simple but ubiquitous test. Received: 10 July 2000 / Accepted: 10 July 2000     

Quality assurance in daily practice

 A report based on the workshop on "Quality Assurance in Daily Practice", organised by the study group "Quality Assurance and Accreditation" from the Division of Analytical Chemistry of the Federation of European Chemical Societies (SGQAA/DAC/FECS) held at the EUROANALYSIS-10 conference in Basle, 6–11 September 1998.     

ISO 17025 quality system in a university environment

The experience of working under an ISO 17025 compliant quality system in a university environment is described in the example of the Testing Centre of University of Tartu. University-specific features of the quality system include that the Testing Centre acts as the “quality system server” for other units of the university and graduate students participate in the work carried out under the quality system. The benefits for the university and the graduate students are discussed. It is concluded that implementation of an ISO 17025 compatible quality system in a university is fully accomplishable and gives significant added value to the university by helping to destroy the ivory tower perception about universities and by introducing real-world flavour into the studies and broaden the minds (quality awareness) of the students.     

Regulatory compliance vs. NEXUS quality for laboratory tests

In the U.S., all clinical laboratory testing is regulated by the Clinical Laboratory Improvement Amendments (CLIA) (). The CLIA link test quality and adherence to a body of testing regulations intended to ensure accurate, reliable, and timely patient test results. The goal of the CLIA legislation was to ensure a minimum, fundamental level of quality. In the context of “NEXUS,” quality must “go beyond getting the ‘right’ answer on the ‘right’ patient that can be interpreted against ‘right’ reference values. CLIA regulations with specific minimum, performance requirements, or safeguards, are designed to prevent testing errors. The US Institute of Medicine found that testing processes fail as a result of human error, lack of documentation, and lack of test management. In the latest (2004) interpretations of CLIA regulations, the minimum quality control requirement continues to be analyzing at least two external, liquid quality control materials per test per day. In 1995, we proposed that the responsibility for achieving quality test results shifts from the sole purview of the laboratory director to an “alliance” of laboratory professionals, manufacturers, and regulators. The EQC (equivalent quality control) concept as proposed is a positive step in achieving this alliance. With the obvious lack of scientific and statistical robustness, EQC falls far short of ensuring quality. Achieving the “NEXUS Vision” for quality laboratory testing will not come solely from laboratory professionals. The NEXUS is about how to ensure the full-quality assessment of the testing process – pre-analytical, analytical, and post-analytical.Presented at the 10th Conference Quality in the Spotlight, March 2005, Antwerp, Belgium.     

Implementation of a ”data filter” for the UK National Marine Monitoring Programme

The implementation of a strategy for the assessment of the validity of environmental monitoring data – a ”data filter”– is described. The approach was developed through the UK National Marine AQC Scheme for application to data collected during the UK National Marine Monitoring Programme. Data reported for the year 1999, by nine laboratories, for 74 determinand-matrix combinations were assessed on the basis of the completeness of their supporting quality assurance and quality control information. The approach to the establishment of criteria of acceptability for quality information is described. Received: 28 August 2001 Accepted: 29 November 2001     

A new terminology for the approaches to the quantification of the measurement uncertainty

A new terminology for the approaches to the quantification of the measurement uncertainty is presented, with a view to a better understanding of the available methodologies for the estimation of the measurement quality and differences among them. The knowledge of the merits, disadvantages and differences in the estimation process, of the available approaches, is essential for the production of metrologically correct and fit-to-purpose uncertainty estimations. The presented terminology is based on the level of the analytical information used to estimate the measurement uncertainty (e.g., supralaboratory or intralaboratory information), instead of the direction of information flow (“bottom-up” or “top-down”) towards the level of information where the test is performed, avoiding the use of the same designation for significantly different approaches. The proposed terminology is applied to the approaches considered on 19 examples of the quantification of the measurement uncertainty presented at the Eurachem/CITAC CG4 Guide, Eurolab Technical Report 1/2002 and Nordtest Technical Report 537. Additionally, differences of magnitude in the measurement uncertainty estimated by various approaches are discussed.     

Quality assurance in research laboratories

During the last decade, it has become increasingly important that researchers demonstrate that research is conducted to the highest standards. The implementation of quality assurance for research laboratories will enable all fields of research and development to be judged impartially. There are no specific standards for research laboratories but where possible, existing standards can be adapted. This review is structured around two approaches. The first considers research to be a logical extension of testing, and it is assumed that testing standards can be applied methodically to each step in a research project. The second advocates a flexible approach, with research-specific criteria for assessing quality. The important papers published on this topic have been reviewed. The conclusions are that the general quality management approach, encompassed by the ISO 9000 series of standards with the emphasis on customer satisfaction and ‘fitness for purpose’, is suitable for implementing quality assurance in research laboratories.     

Method Development and Validation of a Rapid Determination of Ropinirole in Tablets by LC-UV

A reversed-phase high-performance liquid chromatographic (HPLC) method with UV detection was developed and validated for the determination of ropinirole (ROP) in tablets. The assay utilized UV detection at 250 nm and a Luna CN column (250 × 4.6 mm I.D, 5 μm). The mobile phases were comprised of acetonitrile: 10 mM nitric acid (pH 3.0) (75:25, v/v). Validation experiments were performed to demonstrate linearity, accuracy, precision, limit of quantitation (LOQ), limit of detection (LOD), and robustness. The method was linear over the concentration range of 0.5–10.0 μg mL⁻¹. The method showed good recoveries (99.75–100.20%) and the relative standard deviations of intra and inter-day assays were 0.38–1.69 and 0.45–1.95%, respectively. The method can be used for quality control assay of ropinirole.     

Quality improvement through verbal and written interviews of laboratory employees

 There is a growing awareness of the importance of the human factors involved in total quality management. Tools to monitor and improve the knowledge and skills of all those involved in production processes in medical laboratories are recognized and applied. The effect of providing written information and verbal presentations concerning specific items (such as documentation, standard operating procedures, etc.) was monitored through an external questionnaire. Not only the level of information but also the employees' perception of their own work gained in depth and positivity. Received: 10 July 2000 / Accepted: 10 July 2000     

Quality improvement in wellness reports in patients with Crohn’s disease

Quality-of-life tests are used because they provide information about symptoms, potential complications, and response to treatment with patients as active participants. We took Crohn’s disease (CD) during diet supplement with omega 3 or 6 fatty acids (ω-3FA vs. ω-6FA) Impact^® as an example and assessed three quality-of-life tests: The inflammatory bowel disease questionnaire (IBDQ), the Beck depression inventory (BDI), and the visual analogue scale (VAS). These tests have been found inconvenient, not informative in daily clinical use, and inhomogeneous in international studies.We used the body mass index (BMI) (kg/m²) as a clinical quantitative effect parameter and the patient self-rated quality of life as qualitative variables during recovery. All ratings were converted into numeric standardized percent point before isolation of optimized ratings.BMI increased on average 2 BMI units in both diet groups. The classical wellness tests or their traditional sub-scores identified improved outcome during recovery, primarily in the ω-3FA group. Separate items on bowel function, wellness, and asthenia possessed the best item responsiveness – (30–35 percent point). A new selective scale with the six most responsive items is proposed as a specific optimized questionnaire.Based on CD as an example, we described a method to isolate responsive items from quality-of-life tests and described a method to optimize their sensitivity. We propose for validation a new optimized disease – specific VAS scale for rating of wellness during treatment in inflammatory bowel disease, in which ω-3FA seemed superior in improving outcome.Presented at the 10th Conference Quality in the Spotlight, March 2005, Antwerp, Belgium.     

The Russian system for accreditation of analytical laboratories (centers)

 The history and the present state of the national system for accreditation of analytical laboratories in Russia are described. Received: 1 September 1998 / Accepted: 1 September 1998     

Application of inductively coupled plasma–mass spectrometry (ICP–MS) and quality assurance to study the incorporation of strontium into bone,bone marrow,and teeth of dogs after one month of treatment with strontium malonate

The strontium content of serum, bone, marrow, and teeth was determined by inductively-coupled plasma mass spectrometry (ICP–MS). Significant correlations were obtained after the data were subjected to quality assurance (QA) performed according to validated procedures. After four weeks of treatment with strontium malonate, strontium levels increased from 76 ± 9 μg g⁻¹ in placebo-treated dogs to levels of 7.2 ± 1.7 mg g⁻¹, 9.5 ± 2.7 mg g⁻¹, and 9.8 ± 2.7 mg g⁻¹ in groups treated with 300, 1000, and 3000 mg kg⁻¹ day⁻¹, respectively. Strontium induced a highly significant increase in the bone formation marker, bone-specific alkaline phosphatase (BSAP), and an excellent correlation was found with the bone-strontium content. In females, the placebo-treated group showed a decrease in BSAP of 53%, whereas the three strontium malonate-treated groups showed an increase of 60, 276, and 278% for the groups treated with 300, 1000, and 3000 mg kg⁻¹ day⁻¹, respectively. For males the corresponding values were −44%, +142%, +194%, and +247% increases in BSAP in the placebo, 300, 1000, and 3000 mg kg⁻¹ day⁻¹ groups respectively.     

Key requirements for introducing quality assurance in measurement laboratories

 The implementation of a quality assurance system is fraught with difficulties. However, these difficulties may be overcome if the laboratory uses suitable means to facilitate the process. It is necessary to mobilise the intelligence and energy of all members of the laboratory. In order to command adherence, the project must be shared, and this necessitates a major effort by all concerned. Communication is a major factor in obtaining the support of all parties. Six important steps must be distinguished: – Defining quality policy – Creating awareness, information, training – Creating a quality structure – Establishing a deadline for obtaining accreditation – Progressive implementation – Experimentation and validation. Even if the task of obtaining and maintaining accreditation remains difficult, it clearly promotes a minimum level of organisation and stepwise progress in quality assurance. The laboratory must keep improving its quality system, using European Standard EN 45001 as an effective management model. Received: 9 April 1997 · Accepted: 11 September 1997     

The new ISO 17025 – basic idea

 This paper offers a concise overview of the recent draft of ISO 17025, which is expected to replace EN 45001 in 1999. Reference is made to the general area of related ISO standards for management systems. The main changes compared with EN 45001 are discussed for testing laboratories.     

RP-HPLC determination of midecamycin and related impurities

Summary A method has been developed for separation and quantitation of midecamycin A₁ and related impurities by high-performance liquid chromatography with evaporative light-scattering detection (ELSD). Chromatographic conditions included use of a Diamonsil C₁₈ column; the mobile phase was 52:48 acetonitrile −0.2 mol L⁻¹ ammonium formate solution (adjusted to pH 7.3 with triethylamine) at a flow rate of 1 mL min⁻¹. The column temperature was 35°C, the shift tube temperature of the ELSD was 105°C, and the gas flow rate of the ELSD was 3.0 L min⁻¹. The response factors of midecamycins in HPLC-ELSD were the same; the linear equation wasy=599292.44x+2868618.04,r=0.9979, the linear range was 5–80 μg,RSD=0.21–1.54%, and theLOD andLOQ were 0.36 and 1.2 μg, respectively. The method was simple, quick, and precise and could be used to determine midecamycin and its related impurities directly.     

Sediment certified reference materials for the determination of polychlorinated biphenyls and organochlorine pesticides from the National Metrology Institute of Japan (NMIJ)

Two marine sediment certified reference materials, NMIJ CRM 7304-a and 7305-a, have been issued by the National Metrology Institute of Japan in the National Institute of Advanced Industrial Science and Technology (NMIJ/AIST) for the determination of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs). The raw materials of the CRMs were collected from a bay near industrial activity in Japan. Characterization of these CRMs was conducted by NMIJ, where the sediments were analyzed using multiple analytical methods such as pressurized liquid extraction (PLE), microwave-assisted extraction (MAE), saponification, Soxhlet extraction, supercritical fluid extraction (SFE), and ultrasonic extraction; the target compounds were determined by one of the primary methods of measurements, isotope dilution–mass spectrometry (ID-MS). Certified values have been provided for 14 PCB congeners (PCB numbers 3, 15, 28, 31, 70, 101, 105, 138, 153, 170, 180, 194, 206, 209) and 4 OCPs (γ-HCH, 4,4′-DDT, 4,4′-DDE, 4,4′-DDD) in both CRMs. NMIJ CRM 7304-a has concentrations of the contaminants that are a factor of 2–15 greater than in CRM 7305-a. Both CRMs have information values for PCB homolog concentrations determined by collaborative analysis using a Japanese official method for determination of PCBs. The total PCB concentrations in the CRMs are approximately 920 and 86 μg kg⁻¹ dry mass respectively. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

The scope and limitations of a QA system in research

 The article analyses the scope and limitations of quality systems for research centres in the light of the problems involved, foreseen advantages, and growing need created in the context of the globalisation phenomenon. Some propositions are put forward concerning the development of possible quality assurance strategies for research activities. Received: 30 June 1999 / Accepted: 24 September 1999     

The establishment of a quality evaluation system of reference materials

Reference materials have been applied widely to ensure the traceability, comparability and reliability of measurement results. To achieve this purpose, the quality of reference materials (RMs) themselves is surely an important aspect to be pay attention to. A quality evaluation system of RMs has been established through the project “The National Sharing Platform of Reference Materials” in China to give a reliable assessment on the quality of RMs from various sources including the accuracy and comparability of their property values, which is very useful to promote the appropriate selecting and using of RMs in China. Through the application of National Metrology Institute calibration and measurement capabilities on the basis of the international mutual recognition arrangement, it can also provide a powerful supplement to the current activities such as the accreditation of RM producers in the construction of a global harmonized quality control and assurance system of RMs.     

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