National Association Of Testing Authorities Research Articles

Laboratory validation and clinical utility of next-generation sequencing-based IGH/TCR clonality testing for the monitoring of measurable residual disease in acute lymphoblastic leukaemia: real-world experience at Austin Pathology

Measurable residual disease (MRD) testing is an essential aspect of disease prognostication in acute lymphoblastic leukaemia (ALL) and informs clinical decisions. The depth of MRD clearance is highly relevant and requires assays with sufficient sensitivity. Austin Pathology is one of the few laboratories in Australia currently utilising a fully validated and National Association of Testing Authorities (NATA)-accredited ultrasensitive next-generation sequencing (NGS) platform for MRD monitoring in ALL. This technology is based on the detection of clonal rearrangement of immunoglobulin and T cell receptor genes in leukaemic cells, and is capable of achieving a limit of detection at least one to two logs below that of multiparametric flow cytometry (MFC). In this retrospective analysis, we report a clonotype detection rate of up to 85.7% at diagnosis, and a concordance rate of 78.7% in MRD results between NGS and MFC. Of the discordant samples, nearly all were NGS+/MFC-, highlighting the superior sensitivity of NGS. The enhanced sensitivity is clinically relevant, as discordant MRD results often heralded fulminant relapse, and therefore offer clinicians additional lead time and a window of opportunity to initiate pre-emptive therapy. Notwithstanding a small and heterogeneous cohort, our real-world survival data indicate an intermediate relapse risk for NGS+/MFC- patients. In light of recent approval of Medicare rebatable ALL MRD testing, we discuss how NGS can complement other techniques such as MFC in personalising management strategies. We recommend routine clonality testing by NGS at diagnosis and use a multi-modality approach for subsequent MRD monitoring.

First case of mpox diagnosed in Queensland, Australia: clinical and molecular aspects.

First case of mpox diagnosed in Queensland, Australia: clinical and molecular aspects.

Implementing proactive quality assurance quality control (QAQC) and quality management (QM) practices at coal testing laboratories

Many commercial coal testing laboratories are accredited to ISO 17025 – General requirements for the competence of testing and calibration laboratories. There is an expected reliance in the Coal mining industry that the laboratory adheres to all elements of this standard in between successive accreditation audits conducted every 18 months by the independent accreditation body, National Association of Testing Authorities (NATA). In the absence of proactive QAQC & QM practices monitoring the quality of the information reported by laboratories, potential issues impacting production decisions and reconciliation results are only determined in a reactive manner. In addition, for mining companies working with several internal and external laboratories across the supply chain, the management of the logistics, practices and information becomes very challenging and time-consuming, impacting the company’s ability to track laboratory results as key inputs in a production and reconciliation perspective. The absence of proactive QAQC & QM practices results in a sub-optimal/reactive approach in the Coal industry, increasing the risk of short-term unaware production gaps related to quality, increased time required for quality breach investigations, the absence of a holistic approach/monitoring in the value chain, and the financial impact for the business performing under sub-optimal conditions. This paper aims to show the journey towards the implementation of a new proactive QAQC and QM program, where now the quality of many different laboratories across the supply chain can be monitored and linked with global reconciliation results, as an improvement opportunity to complement the current industry standard ISO 17025 accreditation and Proficiency Round Robin approach.

Mainstreaming proteomics into rare disease diagnostics

Mitochondrial diseases are a group of highly heterogeneous disorders caused by mutations in over 350 known genes. Reported genomic diagnostic yields for mitochondrial disorders are in the range of 40–60%. A factor contributing to a lack of molecular diagnosis is the availability of functional tests to demonstrate variant pathogenicity in a timely and cost-effective manner. The gold-standard and National Association of Testing Authorities (NATA)/Royal College of Pathologists of Australasia (RCPA) accredited functional test measures the enzyme activities of mitochondrial respiratory chain complexes I–IV, however this test is not specific as defects in hundreds of genes can lead to an abnormal result.

Experimental investigation of an integrated rainwater harvesting unit for drinking water production at the household level

According to the United Nations' report, billions of people, particularly those living in regional areas (places that lay behind major cities), are still lacking access to clean drinking water. Some of them drink rainwater without any prior treatment even though water experts are campaigning against this practice for potential health risks. As most of the previous studies have focused on the use of harvested rainwater for non-potable usage, the present study reports the feasibility of producing drinking water from an integrated rainwater harvesting unit. It is found that the developed unit can produce clean drinking water for households in rural communities. The economic payback time for the proposed unit is eight years at a water production cost of AU$ 0.07/L. Important quality parameters of the produced drinking water, such as pH, electrical conductivity, ammonia, nitrite, nitrate, total organic carbon, turbidity, faecal coliforms &escherichia coli, heavy metals, and total trihalomethanes, are examined using a testing facility accredited by the National Association of Testing Authorities from Australia. It is found that the water quality complies with the requirements specified in the Australian drinking water guidelines. The developed integrated rainwater harvesting unit could produce drinking water at a capacity of 348 ± 20 L in a day. Since it is important to store the produced drinking water for potential dry periods, suitable methods for disinfection and mineral fortification of the produced water are presented. Finally, a detailed description of the step-by-step installation of the proposed system is presented. This study can potentially contribute to Goal 6: Clean water and sanitation of United Nations' Sustainable Development Goals.

Gamma-Glutamyl Transferase (GGT) Is the Leading External Quality Assurance Predictor of ISO15189 Compliance for Pathology Laboratories.

Pathology results are central to modern medical practice, informing diagnosis and patient management. To ensure high standards from pathology laboratories, regulators require compliance with international and local standards. In Australia, the monitoring and regulation of medical laboratories are achieved by conformance to ISO15189-National Pathology Accreditation Advisory Council standards, as assessed by the National Association of Testing Authorities (NATA), and an external quality assurance (EQA) assessment via the Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP). While effective individually, integration of data collected by NATA and EQA testing promises advantages for the early detection of technical or management problems in the laboratory, and enhanced ongoing quality assessment. Random forest (RF) machine learning (ML) previously identified gamma-glutamyl transferase (GGT) as a leading predictor of NATA compliance condition reporting. In addition to further RF investigations, this study also deployed single decision trees and support vector machines (SVM) models that included creatinine, electrolytes and liver function test (LFT) EQA results. Across all analyses, GGT was consistently the top-ranked predictor variable, validating previous observations from Australian laboratories. SVM revealed broad patterns of predictive EQA marker interactions with NATA outcomes, and the distribution of GGT relative deviation suggested patterns by which to identify other strong EQA predictors of NATA outcomes. An integrated model of pathology quality assessment was successfully developed, via the prediction of NATA outcomes by EQA results. GGT consistently ranked as the best predictor variable, identified by combining recursive partitioning and SVM ML strategies.

An assessment of a pressure impregnated, full-penetration, fire resisting chemical treatment for Laminated Veneer Lumber

ABSTRACTSince 1901, there have been over 260 bushfires in Australia and over 825 known civilian and firefighter fatalities. The present study assessed the material properties and fire resistance qualities (to BAL 29) of a full-penetration, pressure impregnated, intumescent fire retardant treated Laminated Veneer Lumber (LVL) for use in building environments not exposed to weathering – i.e. subfloor systems. The testing was carried out in accordance with AS3959:2009 utilising a Cone Calorimeter device at a National Association of Testing Authorities accredited laboratory. The results indicate that the samples subjected to testing meet the criteria of AS/NZS3837 Appendix F, meeting the necessary performance criteria for bushfire-resisting materials. The full-penetration, pressure impregnated, intumescent fire retardant treated LVL is suitable for the construction of structures in bushfire prone areas to Bushfire Attack Level 29 (BAL29).

Revalidation

Revalidation of medical practitioners already occurs in many countries, including the UK, Canada and America. However, forensic pathologists in America have expressed dissatisfaction with the use of examinations and the system in the UK is regarded by some as too onerous. The Australia Health Practitioners Agency (AHPRA) is planning to introduce revalidation. In preparation, the Royal College of Pathologists of Australasia (RCPA) formed a steering group to develop Internal Quality Assurance programmes that would meet the needs of revalidation without incurring extra work for practising pathologists. Three areas were considered: pre-analytical, analytical and post-analytical. Within forensic pathology the pre-analytical conditions are mostly dictated and are beyond control. Post-analytical would largely be regarded as court work, but it would be inappropriate to judge pathologists against outcome, as expert evidence must be independent. As forensic pathology is an opinion-based specialty, peer review would be the best method to assess standards. This is already a National Association of Testing Authorities (NATA) requirement. Initial consultation by AHPRA regarding revalidation suggests that peer review will be promoted. Thus, for forensic pathology a system of peer review is proposed.

Clinical validation of the 50 gene AmpliSeq Cancer Panel V2 for use on a next generation sequencing platform using formalin fixed, paraffin embedded and fine needle aspiration tumour specimens

The advent of massively parallel sequencing has caused a paradigm shift in the ways cancer is treated, as personalised therapy becomes a reality. More and more laboratories are looking to introduce next generation sequencing (NGS) as a tool for mutational analysis, as this technology has many advantages compared to conventional platforms like Sanger sequencing. In Australia all massively parallel sequencing platforms are still considered in-house invitro diagnostic tools by the National Association of Testing Authorities (NATA) and a comprehensive analytical validation of all assays, and not just mere verification, is a strict requirement before accreditation can be granted for clinical testing on these platforms. Analytical validation of assays on NGS platforms can prove to be extremely challenging for pathology laboratories. Although there are many affordable and easily accessible NGS instruments available, there are no standardised guidelines as yet for clinical validation of NGS assays. We present an accreditation development procedure that was both comprehensive and applicable in a setting of hospital laboratory for NGS services. This approach may also be applied to other NGS applications in service laboratories.

Performance monitoring and transfusion QAP performance levels

This presentation will endeavour to provide an understanding of Performance Monitoring in Quality Assurance of Transfusion as measured by a project undertaken by the Royal College of Pathologists of Australasia (RCPA) Quality Assurance Program (QAP) in 2012. In 2001 the Commonwealth Department of Health and Ageing (DoHA) sought proposals to undertake an evaluation of Australian pathology laboratory accreditation arrangements. Recommendations from the report were that (1) the DoHA and the Health Insurance Commission seek the cooperation of the RCPA QAP to establish explicit external quality assurance performance criteria and a mechanism for the RCPA QAP to identify relatively poorly performing laboratories; (2) RCPA QAP and other external quality assurance providers regularly submit to the National Association of Testing Authorities (NATA) reports identifying laboratories that are poorly performing according to these agreed performance criteria. The review process included establishment of a methodology/scoring system; a retrospective data analysis; establishment of criteria for acceptable performance based on the retrospective data analysis and reasonable expectations for completing a corrective action. Information and results from QAP surveys was used to assess individual participant data against established criteria to provide laboratories of an objective measure of their performance relative to their peers whilst meeting the needs of the performance review process.

Monitoring performance of external quality control

Aim In 2010 the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPA QAP), received Quality Use of Pathology Program funding to determine if regular external quality assurance that laboratories perform could be used to identify unacceptable performance earlier than the usual 3 year NATA accreditation cycle, to help minimise risk to patients. Method Criteria for unacceptable performance have been established to identify laboratories that maybe underperforming in external quality assurance (EQA). New frameworks have also been developed that outline the process of actions to be taken by the RCPA QAP when participant results and IVDs fall outside levels of acceptable performance. The frameworks proactively notify participants or manufacturers or their sponsors to assist them early. Results When unacceptable performance is identified, according to the set criteria, a letter will be sent to the participant outlining the result(s) falling outside the criteria for acceptable performance and offer assistance to review the QAP results. Persisting unacceptable performance will be referred to a Committee for review and results referred to the National Association of Testing Authorities (NATA) or Therapuetic Goods Administration (TGA) for follow-up. Conclusion The RCPA QAP has established a performance monitoring system using the EQA results. The early warning system will identify laboratories of concern and assist them to obtain their accreditation. Conflict of interest statement This research was supported by the Department of Health and Ageing. The Department had no role in analysing the data or preparing the abstract.

Progress report on the file audit project

In June 2011, National Association of Testing Authorities (NATA) commenced the File Audit Project which consists of an analysis of non-conformances identified during its assessments of pathology laboratories against the accreditation standards over the past 3–6 years. Objectives: 1. To provide a meaningful analysis of assessment outcomes particularly with respect to high risk findings and patient safety that may be used to guide future refinement of the pathology accreditation framework. 2. To analyse the trends and patterns in poorly performing laboratories, including examination of corrective actions undertaken by laboratories to address deficiencies. 3. To allow an overview of the breadth of coverage areas of the accreditation materials and highlight areas of potential deficiency. 4. To consider a mechanism for the ongoing collection of data and provision of regular reports to the Department of Health and Ageing on assessment findings to assist with identifying issues and determining trends. A stakeholder and smaller steering groups have been established to provide NATA with guidance and the opportunity to inform stakeholders about the File Audit Project. A risk analysis of the assessment findings are also being recorded for the project. Risk matrix formulae and a ‘risk score’ for each assessment have been established and are being trialled as part of the project.

Performance monitoring in gynaecological cytopathology

Following the establishment of the Cytopathology Performance Review Committee this year, criteria for monitoring laboratory performance have been developed and a pilot phase will be undertaken in 2012. Criteria are based on both results from routine gynaecological Quality Assurance Program (QAP) surveys and Performance Measure data. The pilot phase will help determine the effectiveness of these criteria in assisting the National Association of Testing Authorities (NATA) to identify laboratories that may require early review. Criteria for the pilot are: one Performance Measure outside the National Standard set by NPAAC; non-submission of results for Performance Measures; one major error in a conventional gynaecological (GYN) survey; three unacceptable responses in any GYN survey in any 12 month period; non-submission of results for any GYN survey. Results will be reviewed within a rolling 12 month cycle. When a laboratory’s results have fallen outside these established criteria, the laboratory’s results will be forwarded to the Cytopathology Peer Review Committee for review. If results are assessed as unacceptable, notification letters will be sent to the laboratory in accordance with the framework developed by the Royal College of Pathologists of Australasia (RCPA) QAP. It is hoped the outcomes of the pilot phase of the Cytopathology Performance Monitoring Project will assist in evaluating criteria for unacceptable performance in Cytopathology. As the project progresses results will be monitored by the Cytopathology PRC and these criteria may be reviewed.

Performance monitoring in anatomical pathology

In 2012, the Royal College of Pathologists of Australasia (RCPA) Anatomical Pathology Quality Assurance Program (QAP) will introduce a pilot for performance monitoring in the General and Breast Diagnostic Modules. The Anatomical Pathology Performance Review Committee has developed a set of criteria for Diagnostic Pathology assessment. If any of the following criteria apply, a participant will be considered to be outside criteria for satisfactory performance: <h3>Participation</h3> 1 x survey non-participation. <h3>Performance of test</h3> ≥ 3 x in the bottom 10% survey rank, over 3 years; thereafter, if in bottom 10% rank subsequently. Average survey rank ≤10%, over 3 years; thereafter, if average survey rank is < the average survey rank on the previous survey; thereafter reset scoring if > 10% 3 x consecutively. If average discordant sum is ≥1.50 AND number of surveys completed is ≥2 (in rolling 12 month period); thereafter, if ≥1.50 AND ≥2 surveys completed AND survey contains discordant result. ≥5 non-concordant results per survey. <h3>Notification</h3> RCPA QAP response to notifiable unsatisfactory performance will initially take the form of letter to participants; subsequent deviations from the outlined criteria may result in copies of notifications forwarded also to National Association of Testing Authorities (NATA).

Detection of s-triazine pesticides in natural waters by modified large-volume direct injection HPLC

There is a need for simple and inexpensive methods to quantify potentially harmful persistent pesticides often found in our water-ways and water distribution systems. This paper presents a simple, relatively inexpensive method for the detection of a group of commonly used pesticides (atrazine, simazine and hexazinone) in natural waters using large-volume direct injection high performance liquid chromatography (HPLC) utilizing a monolithic column and a single wavelength ultraviolet–visible light (UV–vis) detector. The best results for this system were obtained with a mobile phase made up of acetonitrile and water in a 30:70 ratio, a flow rate of 2.0 mL min −1, and a detector wavelength of 230 nm. Using this method, we achieved retention times of less than three minutes, and detection limits of 5.7 μg L −1 for atrazine, 4.7 μg L −1 for simazine and 4.0 μg L −1 for hexazinone. The performance of this method was validated with an inter-laboratory trial against a National Association of Testing Authorities (NATA) accredited liquid chromatography–mass spectrometry/mass spectrometry (LC–MS/MS) method commonly used in commercial laboratories.

What does NATA do about poorly performing labs?

The accreditation program for pathology laboratories in Australia is a joint scheme of the National Association of Testing Authorities (NATA) and the Royal College of Pathologists of Australasia (RCPA) which has offered accreditation in the pathology sector for over 25 years. Whilst the program seeks to engender a culture of continual improvement within pathology, there is also an obligation and duty of care to identify those laboratories which do not meet the accreditation requirements and where patient results might be compromised. NATA has formal processes in place to handle poor performance in laboratories – a series of steps is taken including conducting follow-up assessments, suspending accreditation and, ultimately, cancelling accreditation. The ways in which poor performance is identified at assessment will be discussed together with the common areas which feature in poorly performing laboratories. Compliance with accreditation requirements for new laboratories as well as those which have been operating for a number of years is a key issue for all laboratories who seek benefits from Medicare Australia. Continued poor performance will impact on the laboratory’s access to these benefits. The accreditation program for pathology laboratories in Australia is a joint scheme of the National Association of Testing Authorities (NATA) and the Royal College of Pathologists of Australasia (RCPA) which has offered accreditation in the pathology sector for over 25 years. Whilst the program seeks to engender a culture of continual improvement within pathology, there is also an obligation and duty of care to identify those laboratories which do not meet the accreditation requirements and where patient results might be compromised. NATA has formal processes in place to handle poor performance in laboratories – a series of steps is taken including conducting follow-up assessments, suspending accreditation and, ultimately, cancelling accreditation. The ways in which poor performance is identified at assessment will be discussed together with the common areas which feature in poorly performing laboratories. Compliance with accreditation requirements for new laboratories as well as those which have been operating for a number of years is a key issue for all laboratories who seek benefits from Medicare Australia. Continued poor performance will impact on the laboratory’s access to these benefits.

Antenatal hepatitis b testing as a marker of quality performance of a laboratory

Quality assurance programs (QAP) provide management with confidence in the accuracy and precision of results reported from their laboratory. Laboratory accreditation by National Association of Testing Authorities (NATA) ensures there are quality systems in place that relate to documentation of techniques and systems of checking processes as well as consistency of reporting accurate results. This overview of the last 2 years of Antenatal Hepatitis B Surface Antigen QAP identifies the common errors, both critical and less critical, while reflecting on the response of errant laboratories to improve their performance. Critical errors have an immediate impact on the patient and include false positive or negative results as well as transcriptions errors and mix-up of specimens (specimen reversal). Other errors, although they may not have an immediate impact on patient results, can still be viewed as a quality system failure and should be investigated with action taken to correct the error and avoid similar errors in future. Other common errors include incorrect cutoff values, incorrect units, expired kits and incorrect lot number information. The Antenatal Hepatitis B QAP covers screening assays for hepatitis B surface antigen, and associated supplemental and confirmatory assays. The importance of reporting these results correctly is paramount for the care of both the mother and infant and a false result, either positive or negative may result in inappropriate management of these patients.

Forensic Analysis of Explosives Using Isotope Ratio Mass Spectrometry (IRMS)—Part 1: Instrument Validation of the DELTAplusXP IRMS for Bulk Nitrogen Isotope Ratio Measurements

A significant amount of research has been conducted into the use of stable isotopes to assist in determining the origin of various materials. The research conducted in the forensic field shows the potential of isotope ratio mass spectrometry (IRMS) to provide a level of discrimination not achievable utilizing traditional forensic techniques. Despite the research there have been few, if any, publications addressing the validation and measurement uncertainty of the technique for forensic applications. This study, the first in a planned series, presents validation data for the measurement of bulk nitrogen isotope ratios in ammonium nitrate (AN) using the DELTA(plus)XP (Thermo Finnigan) IRMS instrument equipped with a ConFlo III interface and FlashEA 1112 elemental analyzer (EA). Appropriate laboratory standards, analytical methods and correction calculations were developed and evaluated. A validation protocol was developed in line with the guidelines provided by the National Association of Testing Authorities, Australia (NATA). Performance characteristics including: accuracy, precision/repeatability, reproducibility/ruggedness, robustness, linear range, and measurement uncertainty were evaluated for the measurement of nitrogen isotope ratios in AN. AN (99.5%) and ammonium thiocyanate (99.99+%) were determined to be the most suitable laboratory standards and were calibrated against international standards (certified reference materials). All performance characteristics were within an acceptable range when potential uncertainties, including the manufacturer's uncertainty of the technique and standards, were taken into account. The experiments described in this article could be used as a model for validation of other instruments for similar purposes. Later studies in this series will address the more general issue of demonstrating that the IRMS technique is scientifically sound and fit-for-purpose in the forensic explosives analysis field.

Proficiency Test for Chemical Laboratories for the Analysis of a Pesticide in a Formulated Product: Interlaboratory Study

A multilaboratory proficiency testing program was conducted by the National Accreditation Board for Testing and Calibration Laboratories (India) and coordinated by the Institute of Pesticide Formulation Technology. This program was conducted to compare the performance of individual laboratories in the area of pesticide formulation (Chlorpyrifos 20 EC) analysis. A total of 24 laboratories in India participated. Analysis of 2 parameters (i.e., estimation of the active ingredient and the acidity) of 2 samples of Chlorpyrifos 20 EC was the objective of this program. Homogeneity tests were performed before sample distribution. Performance of the participating laboratories was evaluated by using new robust statistics given in the guidelines of the National Association of Testing Authorities, Australia. Results were collated and statistically computed to calculate the value of 2 types of Z-scores (Zwi and Zbi). In addition to the statistical analysis, a graphical representation such as the Youden plot was also generated to evaluate the performance of participating laboratories.

The Design and Implementation of the RANZCR/NATA Accreditation Program for Australian Radiology Practices

This paper describes the design, development, and implementation of a voluntary national accreditation program for diagnostic imaging and radiology practices in Australia and the benefits it brings to stakeholders. It discusses the infrastructure and governance developed by the Royal Australian and New Zealand College of Radiologists (RANZCR) and National Association of Testing Authorities (NATA), the implementation issues, the accreditation standards, the accreditation processes, the collaborative roles of the related organizations and programs, the challenges ahead, and the ongoing improvement opportunities.