Airborne fungal spore monitoring: between analyst proficiency testing

Aerobiologia - This study presents the results of a Europe-wide training and Quality Control (QC) exercise carried out within the framework of the European Aerobiology Society’s QC Working...     

Quality control issues in point of care testing

* Quality Control (QC) in Point of Care Testing (PoCT) is often thought of as a complex issue; however intelligent system analysis can simplify matters and greatly increase the chances of a well controlled system. What we want to achieve is a QC program which adequately controls the PoCT system, but does not excessively contribute to the operating costs or complexity of maintaining a PoCT instrument, or network of instruments. * Don't neglect effective pre-analytical work: good documentation, operator training, monitoring, and analyser maintenance programs are essential, as for any analyser. * Look closely at your analyser: Is it a "laboratory type" instrument or cartridge or strip based? Can it perform multiple test types or a single test only? How is it calibrated? Does it have built in self-check capabilities or an electronic check cartridge? Is the sample in contact with the instrument? What are the cartridge/strip/reagent storage requirements? * Establish where the analysis is taking place and which system component is involved. * Tailor your QC program to target this component, but still check the system as a whole. * A common approach is to check cartridges/strips on delivery and run a QA sample at least monthly to check storage conditions and operator performance. If there is no independent electronic instrument check, daily QC checks are also recommended. * Don't be afraid to stray beyond conventional QC models if necessary. Some PoCT systems are not adequately controlled by the application of conventional QC alone.     

Multicenter cell processing for cardiovascular regenerative medicine applications: the Cardiovascular Cell Therapy Research Network (CCTRN) experience

Background aimsMulticenter cellular therapy clinical trials require the establishment and implementation of standardized cell-processing protocols and associated quality control (QC) mechanisms. The aims here were to develop such an infrastructure in support of the Cardiovascular Cell Therapy Research Network (CCTRN) and to report on the results of processing for the first 60 patients.MethodsStandardized cell preparations, consisting of autologous bone marrow (BM) mononuclear cells, prepared using a Sepax device, were manufactured at each of the five processing facilities that supported the clinical treatment centers. Processing staff underwent centralized training that included proficiency evaluation. Quality was subsequently monitored by a central QC program that included product evaluation by the CCTRN biorepositories.ResultsData from the first 60 procedures demonstrated that uniform products, that met all release criteria, could be manufactured at all five sites within 7 h of receipt of BM. Uniformity was facilitated by use of automated systems (the Sepax for processing and the Endosafe device for endotoxin testing), standardized procedures and centralized QC.ConclusionsComplex multicenter cell therapy and regenerative medicine protocols can, where necessary, successfully utilize local processing facilities once an effective infrastructure is in place to provide training and QC.     

Control charting instrumental analyses

Control chart methodology has important applications in the analytical chemistry laboratory. This paper explores application of statistical process control (SPC) techniques to chemical measuring systems and highlights problems when data are correlated. Instrumental methods of chemical analysis typically generate correlated quality-control (QC) sample data owing to the effect of calibration. That is, QC sample measurements stemming from the same calibration curve will tend to be more closely related than measurements derived from different calibration curves. Data correlation will bias the estimated sample variance and essentially invalidate the control limits if not accounted for. A way of calculating statistically valid control limits in the presence of intraclass correlation is examined and an illustrative example given.     

Estimation of the Optimal Statistical Quality Control Sampling Time Intervals Using a Residual Risk Measure

Background

An open problem in clinical chemistry is the estimation of the optimal sampling time intervals for the application of statistical quality control (QC) procedures that are based on the measurement of control materials. This is a probabilistic risk assessment problem that requires reliability analysis of the analytical system, and the estimation of the risk caused by the measurement error.

Methodology/Principal Findings

Assuming that the states of the analytical system are the reliability state, the maintenance state, the critical-failure modes and their combinations, we can define risk functions based on the mean time of the states, their measurement error and the medically acceptable measurement error. Consequently, a residual risk measure rr can be defined for each sampling time interval. The rr depends on the state probability vectors of the analytical system, the state transition probability matrices before and after each application of the QC procedure and the state mean time matrices. As optimal sampling time intervals can be defined those minimizing a QC related cost measure while the rr is acceptable. I developed an algorithm that estimates the rr for any QC sampling time interval of a QC procedure applied to analytical systems with an arbitrary number of critical-failure modes, assuming any failure time and measurement error probability density function for each mode. Furthermore, given the acceptable rr, it can estimate the optimal QC sampling time intervals.

Conclusions/Significance

It is possible to rationally estimate the optimal QC sampling time intervals of an analytical system to sustain an acceptable residual risk with the minimum QC related cost. For the optimization the reliability analysis of the analytical system and the risk analysis of the measurement error are needed.     

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.

     

Evaluation of external RNA controls for the assessment of microarray performance

External RNA controls (ERCs), although important for microarray assay performance assessment, have yet to be fully implemented in the research community. As part of the MicroArray Quality Control (MAQC) study, two types of ERCs were implemented and evaluated; one was added to the total RNA in the samples before amplification and labeling; the other was added to the copyRNAs (cRNAs) before hybridization. ERC concentration-response curves were used across multiple commercial microarray platforms to identify problematic assays and potential sources of variation in the analytical process. In addition, the behavior of different ERC types was investigated, resulting in several important observations, such as the sample-dependent attributes of performance and the potential of using these control RNAs in a combinatorial fashion. This multiplatform investigation of the behavior and utility of ERCs provides a basis for articulating specific recommendations for their future use in evaluating assay performance across multiple platforms.     

Quality leadership and quality control

Different quality control rules detect different analytical errors with varying levels of efficiency depending on the type of error present, its prevalence and the number of observations. The efficiency of a rule can be gauged by inspection of a power function graph. Control rules are only part of a process and not an end in itself; just as important are the trouble-shooting systems employed when a failure occurs. 'Average of patient normals' may develop as a usual adjunct to conventional quality control serum based programmes. Acceptable error can be based on various criteria; biological variation is probably the most sensible. Once determined, acceptable error can be used as limits in quality control rule systems.

A key aspect of an organisation is leadership, which links the various components of the quality system. Leadership is difficult to characterise but its key aspects include trust, setting an example, developing staff and critically setting the vision for the organisation. Organisations also have internal characteristics such as the degree of formalisation, centralisation, and complexity. Medical organisations can have internal tensions because of the dichotomy between the bureaucratic and the shadow medical structures.

     

Quality control and performance of HIV rapid tests in a microbicide clinical trial in rural KwaZulu-Natal

Background

Quality control (QC) and evaluation of HIV rapid test procedures are an important aspect of HIV prevention trials. We describe QC and performance of two rapid tests, Determine™ and Uni-Gold™ used in a microbicide clinical trial in rural KwaZulu-Natal, South Africa.

Methods/Results

Internal QC of both HIV rapid tests was conducted at the trial site using a Uni-Gold control kit (Uni-Gold™Recombigen® HIV). Both assays produced the expected results for a total of 4637 QC tests. Study participants were tested for HIV at screening and, if enrolled, at regular time points throughout the study. Positive or discordant results were confirmed by a double HIV immunoassay testing strategy at a local laboratory. Overall, 15292 HIV rapid test were performed. Sensitivity and specificity of Determine was 98.95% (95% CI: 97.72–99.61) and 99.83% (95% CI: 99.70–99.91) respectively [positive predictive value (PPV) 97.91% (95% CI: 96.38–98.92)], for Uni-Gold it was 99.30% (95% CI: 98.21–99.81) and 99.96% (95% CI: 99.88–99.99) respectively [PPV 99.47% (95% CI: 98.46–99.89)].

Conclusions

The results suggest that a Uni-Gold control kit can be used for internal QC of both Uni-Gold and the HIV-1 component of the Determine rapid tests. Both rapid tests performed proficiently in the trial population.     

The use of latex beads in external quality assurance and internal quality control for routine semen analysis

The usefulness of latex beads of defined concentration was assessed as a substitute for sperm in the performance of External Quality Assurance (EQA) and Internal Quality Control (IQC) of semen analysis. Within the EQA programme, mean±SEM bias (%) was significantly reduced in 2007 compared to 2002 for both specialist (6.0%±5.4% vs. 55.0%±5.9%) and non-specialist (18.4%±5.9% vs. 90.9%±13.4%) laboratories (both p<0.0001), indicating improved accuracy over time. Within the IQC programme, the beads were used in the appraisal of two scientists, one experienced and one inexperienced, against a known standard. Beads were also used to calibrate eleven counting chambers, resulting in one old chamber being discarded due to its poor performance. The present study has shown that the use of a defined concentration of beads is an excellent adjunct to IQC and EQA programmes enabling the performance of both people and equipment to be assessed in an objective manner.     

建立医疗质量持续改进长效机制的实践与体会

探讨建立医疗质量持续改进长效机制,确保患者医疗安全,提高患者满意度。坚持将健全组织、完善制度、优化流程、全员培训、全面监控、加强沟通、整改到位等措施,贯穿于基础质量控制、环节质量控制和终末质量控3个环节,是建立医疗质量持续改进长效机制的有效方法。     

MDQC: a new quality assessment method for microarrays based on quality control reports

MOTIVATION: The process of producing microarray data involves multiple steps, some of which may suffer from technical problems and seriously damage the quality of the data. Thus, it is essential to identify those arrays with low quality. This article addresses two questions: (1) how to assess the quality of a microarray dataset using the measures provided in quality control (QC) reports; (2) how to identify possible sources of the quality problems. RESULTS: We propose a novel multivariate approach to evaluate the quality of an array that examines the 'Mahalanobis distance' of its quality attributes from those of other arrays. Thus, we call it Mahalanobis Distance Quality Control (MDQC) and examine different approaches of this method. MDQC flags problematic arrays based on the idea of outlier detection, i.e. it flags those arrays whose quality attributes jointly depart from those of the bulk of the data. Using two case studies, we show that a multivariate analysis gives substantially richer information than analyzing each parameter of the QC report in isolation. Moreover, once the QC report is produced, our quality assessment method is computationally inexpensive and the results can be easily visualized and interpreted. Finally, we show that computing these distances on subsets of the quality measures in the report may increase the method's ability to detect unusual arrays and helps to identify possible reasons of the quality problems. AVAILABILITY: The library to implement MDQC will soon be available from Bioconductor.     

Regional Variation in Analytical Techniques used in the Diagnosis and Monitoring of Porphyria: a Case for Harmonisation?

Background:The Royal College of Pathologists of Australasia (RCPA) Porphyrin Quality Assurance Program assesses the measurement of urine, faecal, plasma and whole blood porphyrins and their components plus urinary porphobilinogen and delta aminolaevulinic acid and has laboratories enrolled from around the world. It was observed that there was a wide scatter in results submitted to some subsections of the program.Methods:A detailed questionnaire covering the analytical techniques used in the diagnosis of porphyria was sent to all laboratories enrolled in the RCPA Porphyrin Quality Assurance Program. Additionally, self-enrolment data over a five year period was examined for trends/changes in standardisation, reagent sources and analytical technique.Results:Twenty of the 45 laboratories enrolled in the Porphyrin Quality Assurance Program completed the survey, providing a snapshot of the analytical techniques used world-wide. Post survey self enrolment data indicated only little or no noticeable changes to analytical standardisation of techniques despite the continual lack of agreement of results in subsections of the External Quality Assurance program.Conclusions:While some aspects of porphyria testing are relatively consistent between laboratories, other diagnostic techniques vary widely. A wide variety of individualised reference intervals and reporting techniques is currently in use world-wide. While most of the participants in the survey are regional reference centres specialising in the diagnosis of porphyria and, as such, their diagnostic capability is not in question, international guidelines or global harmonisation of analytical techniques should allow better inter-laboratory comparisons to be made, ultimately improving diagnostic accuracy.     

Head and neck cancer in the UK: what is expected of cytopathology?

Objective:  This review highlights the role of cytopathology in cancer management within UK Head and Neck Cancer Networks and informs on the issues raised by recent UK Department of Health documents and other UK professional guidance. UK guidance requires the formal involvement of cytopathologists within multidisciplinary cancer teams, with medical and non-medical cytopathology staff setting up and running rapid access lump clinics, and support for image-guided fine needle aspiration cytology (FNAC) services. UK guidance also makes recommendations for training, resources and quality control. This review also highlights the resource gap between best practice evidence-based guidance for head and neck (HN) cancer services and existing UK provision for cytopathology, as evidenced by lack of availability of experienced staff and adequacy of training and quality control (QC). Finally, it stresses the importance in the UK of the Royal College of Pathologists' guidance, which defines the need for training, the experience needed for new consultants, the requirements for audit and QC. The implications for the additional resources required for HN cancer cytopathology services are discussed. Recent professional guidance specifying the provision of HN cancer services in the UK includes a cytopathology service for cancer networks, such as rapid access FNAC clinics. Although these clinics already operate in some institutions, there are many institutions where they do not and where the provision of cytopathology services would have to be restructured. This would need the support of local cancer networks and their acceptance of the detailed requirements for cytopathology, including resources, training and QC. The standards are not defined locally, as Strategic Health Authorities and Primary Care Trusts have been instructed by the Department of Health to support, invest and implement them.     

Technical External Quality Assessment for SurePath® stained liquid-based cytology gynaecological cervical samples using control material – a novel approach

Aims and objective: The Technical External Quality Assessment Scheme (TEQA) introduced in Wales is based on NHSCSP publication No 19 [External Quality Assessment Scheme for the Evaluation of Papanicolaou Staining in Cervical Cytology] which sets out the policies and standard operating procedures for the TEQA of Papanicolaou staining of gynaecological cervical samples. As part of a development plan for the TEQA scheme in Wales, the use of a control sample was introduced to the assessment process – a common control sample can provide a consistent assessment parameter independent of the recommended slide selection process [External Quality Assessment Scheme for the Evaluation of Papanicolaou Staining in Cervical Cytology, NHSCSP Publication No 19, February 2004] enabling direct comparison of staining standards for laboratories within the region; this counters selection variation bias, establishing a process that may be more representative of routine staining results. Methods: A cervical sample was selected in line with the criteria described in publication 19 [External Quality Assessment Scheme for the Evaluation of Papanicolaou Staining in Cervical Cytology, NHSCSP Publication No 19, February 2004]. Thirteen slides were prepared by the scheme facilitator from this anonymized sample. These control slides were subsequently ‘fixed’ but not stained, then distributed to the laboratories participating in the TEQA scheme. The slides were stained using their standard regime, then returned to the facilitator for assessment. The slides showed consistent staining with no significant inter‐laboratory variation, however, the eosinophilic stained components exhibited an artificial colouration, which slightly altered the expected stained appearance; this was thought to be due to ‘cross‐reactivity’ of the spray fixative with the preserving agent. To address this artefact, a further development of control procedures was devised utilizing a pooled control sample procedure. Residual material from a number of similar samples was pooled and distributed in aliquots to participant laboratories for standard processing and staining; the completed slides were returned to the scheme facilitator for assessment. Results: The pooled sample slides were assessed at the next scheduled quarterly TEQA assessment. The overall scoring for these samples produced an acceptable level of Papanicolaou staining for 12 of the laboratories – only one laboratory produced a marginal score. The artefactual presentation of eosinophilia was not seen. Discussion/conclusion: This method of producing control material establishes consistency in the TEQA comparative assessment process, counters selection bias and reduces the time demands associated with slide selection. It may also prove useful in identifying technical problems within laboratories during sample preparation prior to or during staining, including equipment or process faults. This technique is now well established locally as an enhancement of the current TEQA scheme for the assessment of slide staining. We feel that this enhancement could be incorporated as a new initiative in the current National TEQA scheme as a complement to the established selection process.     

The OSCAR-IB consensus criteria for retinal OCT quality assessment

Background

Retinal optical coherence tomography (OCT) is an imaging biomarker for neurodegeneration in multiple sclerosis (MS). In order to become validated as an outcome measure in multicenter studies, reliable quality control (QC) criteria with high inter-rater agreement are required.

Methods/Principal Findings

A prospective multicentre study on developing consensus QC criteria for retinal OCT in MS: (1) a literature review on OCT QC criteria; (2) application of these QC criteria to a training set of 101 retinal OCT scans from patients with MS; (3) kappa statistics for inter-rater agreement; (4) identification reasons for inter-rater disagreement; (5) development of new consensus QC criteria; (6) testing of the new QC criteria on the training set and (7) prospective validation on a new set of 159 OCT scans from patients with MS. The inter-rater agreement for acceptable scans among OCT readers (n = 3) was moderate (kappa 0·45) based on the non-validated QC criteria which were entirely based on the ophthalmological literature. A new set of QC criteria was developed based on recognition of: (O) obvious problems, (S) poor signal strength, (C) centration of scan, (A) algorithm failure, (R) retinal pathology other than MS related, (I) illumination and (B) beam placement. Adhering to these OSCAR-IB QC criteria increased the inter-rater agreement to kappa from moderate to substantial (0.61 training set and 0.61 prospective validation).

Conclusions

This study presents the first validated consensus QC criteria for retinal OCT reading in MS. The high inter-rater agreement suggests the OSCAR-IB QC criteria to be considered in the context of multicentre studies and trials in MS.     

Pollen monitoring: minimum requirements and reproducibility of analysis

Training, quality assurance (QA) and quality control (QC) play an important role in building competence in monitoring and research in aerobiology. The main goals of this paper were to: (a) formulate an updated Minimum Requirements Report for pollen monitoring; (b) carry out a pilot QC exercise of staff involved in pollen counting from various national networks in order to examine between analysts reproducibility and develop a methodology that can be used in future QC exercises. A questionnaire survey was sent to coordinators of participating pollen monitoring networks. In addition, a total of 45 technicians from 15 European countries participated in the pilot QC exercise. All technicians were instructed to analyse two slides containing the following pollen types: (a) Poaceae and Betula pollen grains in the north of Europe; (b) Poaceae and Olea pollen grains in the south of Europe. Minimum Recommendations were produced based on the results of the questionnaire survey, published literature, and the outcomes of a workshop. In the QC exercise, it was noticed that technicians who followed the Minimum Recommendations and examined at least 10 % of the slide tended to have better indicators of precision and accuracy than those technicians who did not follow the Minimum Recommendations. The proposed Minimum Recommendations will help to improve the quality of scientific work, particularly for those who are considering the setting up of new monitoring sites. The results of the pilot QC exercise will help to develop a methodology that can be used again in the future, thereby ensuring data quality.     

Effects of speed, agility, quickness training method on power performance in elite soccer players

The purpose of this study was to evaluate the effects of the speed, agility, quickness (SAQ) training method on power performance in soccer players. Soccer players were assigned randomly to 2 groups: experimental group (EG; n = 50) and control group (n = 50). Power performance was assessed by a test of quickness--the 5-m sprint, a test of acceleration--the 10-m sprint, tests of maximal speed--the 20- and the 30-m sprint along with Bosco jump tests--squat jump, countermovement jump (CMJ), maximal CMJ, and continuous jumps performed with legs extended. The initial testing procedure took place at the beginning of the in-season period. The 8-week specific SAQ training program was implemented after which final testing took place. The results of the 2-way analysis of variance indicated that the EG improved significantly (p < 0.05) in 5-m (1.43 vs. 1.39 seconds) and in 10-m (2.15 vs. 2.07 seconds) sprints, and they also improved their jumping performance in countermovement (44.04 vs. 4.48 cm) and continuous jumps (41.08 vs. 41.39 cm) performed with legs extended (p < 0.05). The SAQ training program appears to be an effective way of improving some segments of power performance in young soccer players during the in-season period. Soccer coaches could use this information in the process of planning in-season training. Without proper planning of the SAQ training, soccer players will most likely be confronted with decrease in power performance during in-season period.     

Quality assurance and quality control processes: summary of a metabolomics community questionnaire

Introduction

The Metabolomics Society Data Quality Task Group (DQTG) developed a questionnaire regarding quality assurance (QA) and quality control (QC) to provide baseline information about current QA and QC practices applied in the international metabolomics community.

Objectives

The DQTG has a long-term goal of promoting robust QA and QC in the metabolomics community through increased awareness via communication, outreach and education, and through the promotion of best working practices. An assessment of current QA and QC practices will serve as a foundation for future activities and development of appropriate guidelines.

Method

QA was defined as the set of procedures that are performed in advance of analysis of samples and that are used to improve data quality. QC was defined as the set of activities that a laboratory does during or immediately after analysis that are applied to demonstrate the quality of project data. A questionnaire was developed that included 70 questions covering demographic information, QA approaches and QC approaches and allowed all respondents to answer a subset or all of the questions.

Result

The DQTG questionnaire received 97 individual responses from 84 institutions in all fields of metabolomics covering NMR, LC-MS, GC-MS, and other analytical technologies.

Conclusion

There was a vast range of responses concerning the use of QA and QC approaches that indicated the limited availability of suitable training, lack of Standard Operating Procedures (SOPs) to review and make decisions on quality, and limited use of standard reference materials (SRMs) as QC materials. The DQTG QA/QC questionnaire has for the first time demonstrated that QA and QC usage is not uniform across metabolomics laboratories. Here we present recommendations on how to address the issues concerning QA and QC measurements and reporting in metabolomics.