Investigating the Current Harmonization Status of Tumor Markers Using Global External Quality Assessment Programs: A Feasibility Study.

BACKGROUND: The harmonization status of most tumor markers (TMs) is unknown. We report a feasibility study performed to determine whether external quality assessment (EQA) programs can be used to obtain insights into the current harmonization status of the tumor markers α-fetoprotein (AFP), prostate specific antigen (PSA), carcinoembryonic antigen (CEA), cancer antigen (CA)125, CA15-3 and CA19-9. METHODS: EQA sample results provided by 6 EQA providers (INSTAND [Germany], Korean Association of External Quality Assessment Service [KEQAS, South Korea], National Center for Clinical Laboratories [NCCL, China], United Kingdom National External Quality Assessment Service [UK NEQAS, United Kingdom], Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek [SKML, the Netherlands], and the Royal College of Pathologists of Australasia Quality Assurance Programs [RCPAQAP, Australia]) between 2020 and 2021 were used. The consensus means, calculated from the measurement procedures present in all EQA programs (Abbott Alinity, Beckman Coulter DxI, Roche Cobas, and Siemens Atellica), was used as reference values. Per measurement procedure, the relative difference between consensus mean for each EQA sample and the mean of all patient-pool-based EQA samples were calculated and compared to minimum, desirable, and optimal allowable bias criteria based on biological variation. RESULTS: Between 19040 (CA15-3) and 25398 (PSA) individual results and 56 (PSA) to 76 (AFP) unique EQA samples were included in the final analysis. The mean differences with the consensus mean of patient-pool-based EQA samples for all measurement procedures were within the optimum bias criterion for AFP, the desirable bias for PSA, and the minimum bias criterion for CEA. However, CEA results <8 µg/L exceeded the minimum bias criterion. For CA125, CA15-3, and CA19-9, the harmonization status was outside the minimum bias criterion, with systematic differences identified. CONCLUSIONS: This study provides relevant information about the current harmonization status of 6 tumor markers. A pilot harmonization investigation for CEA, CA125, CA15-3, and CA19-9 would be desirable.

Machine Learning in Laboratory Medicine: Recommendations of the IFCC Working Group.

BACKGROUND: Machine learning (ML) has been applied to an increasing number of predictive problems in laboratory medicine, and published work to date suggests that it has tremendous potential for clinical applications. However, a number of groups have noted the potential pitfalls associated with this work, particularly if certain details of the development and validation pipelines are not carefully controlled. METHODS: To address these pitfalls and other specific challenges when applying machine learning in a laboratory medicine setting, a working group of the International Federation for Clinical Chemistry and Laboratory Medicine was convened to provide a guidance document for this domain. RESULTS: This manuscript represents consensus recommendations for best practices from that committee, with the goal of improving the quality of developed and published ML models designed for use in clinical laboratories. CONCLUSIONS: The committee believes that implementation of these best practices will improve the quality and reproducibility of machine learning utilized in laboratory medicine. SUMMARY: We have provided our consensus assessment of a number of important practices that are required to ensure that valid, reproducible machine learning (ML) models can be applied to address operational and diagnostic questions in the clinical laboratory. These practices span all phases of model development, from problem formulation through predictive implementation. Although it is not possible to exhaustively discuss every potential pitfall in ML workflows, we believe that our current guidelines capture best practices for avoiding the most common and potentially dangerous errors in this important emerging field.

Benefits, limitations, and controversies on patient-based real-time quality control (PBRTQC) and the evidence behind the practice.

BACKGROUND: In recent years, there has been renewed interest in the "old" average of normals concept, now generally referred to as moving average quality control (MA QC) or patient-based real-time quality control (PBRTQC). However, there are some controversies regarding PBRTQC which this review aims to address while also indicating the current status of PBRTQC. CONTENT: This review gives the background of certain newly described optimization and validation methods. It also indicates how QC plans incorporating PBRTQC can be designed for greater effectiveness and/or (cost) efficiency. Furthermore, it discusses controversies regarding the complexity of obtaining PBRTQC settings, the replacement of iQC, and software functionality requirements. Finally, it presents evidence of the added value and practicability of PBRTQC. OUTLOOK: Recent developments in, and availability of, simulation methods to optimize and validate laboratory-specific PBRTQC procedures have enabled medical laboratories to implement PBRTQC in their daily practice. Furthermore, these methods have made it possible to demonstrate the practicability and added value of PBRTQC by means of two prospective "clinical" studies and other investigations. Although internal QC will remain an essential part of any QC plan, applying PBRTQC can now significantly improve its performance and (cost) efficiency.

Steady state errors and risk of a QC strategy.

BACKGROUND: To minimise the risk of patient harm from results, laboratories should establish QC strategies and monitor the performance of assays in line with the analytical and clinical risk. METHODS: Steady state errors were calculated from a distribution normalized for an Analytical Performance Specification expressed as Assay Capability (imprecision) minus Assay Stability (drift). Inverting this error rate gave QC run length containing one error. Multiplying by error detection of a critical shift gave a QC functional run length for stable and unstable situations. Suitability of this technique was examined using laboratory EQA imprecision and drift data against various analytical and clinical performance specifications. RESULTS: Steady state errors and error detection, and hence QC functional run length, were dramatically affected by worsening imprecision, drift or changing performance specifications. For a single analyser type, laboratory steady state errors against RCPAQAP performance specification ranged over five orders of magnitude, with contributions from Assay Capability and Assay Stability varying by laboratory. CONCLUSIONS: Steady state errors accumulate for all assays. Our functional QC run length based on steady state error rate adjusted for error detection of the QC algorithm, amounts to a risk approach using the first two elements of FMEA-like calculation and allows laboratories to examine the suitability of their combinations of QC run length, algorithm, workload and timing of QC challenges. An appropriate common performance specification is critical when assessing and comparing risk.

Diagnostic Laboratories in India: Investigating Quality Characteristics, Productivity and Time of Reporting.

This is the result of a Survey of diagnostics laboratories in the Asia Pacific (APAC) region with perspectives on India, investigating the three key aspects that are central to the success of a laboratory: quality, cost and speed. This Survey provides a comparison in selected performance indicators in a large number of diagnostic laboratories in a broad range of countries in the APAC region. The Survey provides data on some key performance characteristics such as quality improvement activities, staff productivity and Turnaround Time (TAT). This Survey also demonstrates in India the common issues facing all the laboratories surveyed but also common solutions using a Quality Systems approach which involves Accreditation, customer responsiveness, greater use of IT, automation and Lean principles. Indian laboratories reported less automation and fewer laboratories have Laboratory Information Systems. The productivity by various measures in Indian laboratories was less than in other APAC laboratories. TAT was more commonly monitored in the Indian specimens though there were fewer laboratories compared with the APAC specimens where there were separate TATs for Short Turnaround Time and Routine specimens.

What's to Be Done About Laboratory Quality? Process Indicators, Laboratory Stewardship, the Outcomes Problem, Risk Assessment, and Economic Value: Responding to Contemporary Global Challenges.

OBJECTIVES: For 50 years, structure, process, and outcomes measures have assessed health care quality. For clinical laboratories, structural quality has generally been assessed by inspection. For assessing process, quality indicators (QIs), statistical monitors of steps in the clinical laboratory total testing, have proliferated across the globe. Connections between structural and process laboratory measures and patient outcomes, however, have rarely been demonstrated. METHODS: To inform further development of clinical laboratory quality systems, we conducted a selective but worldwide review of publications on clinical laboratory quality assessment. RESULTS: Some QIs, like seven generic College of American Pathologists Q-Tracks monitors, have demonstrated significant process improvement; other measures have uncovered critical opportunities to improve test selection and result management. The College of Pathologists of Australasia Key Indicator Monitoring and Management System has deployed risk calculations, introduced from failure mode effects analysis, as surrogate measures for outcomes. Showing economic value from clinical laboratory testing quality is a challenge. CONCLUSIONS: Clinical laboratories should converge on fewer (7-14) rather than more (21-35) process monitors; monitors should cover all steps of the testing process under laboratory control and include especially high-risk specimen-quality QIs. Clinical laboratory stewardship, the combination of education interventions among clinician test orderers and report consumers with revision of test order formats and result reporting schemes, improves test ordering, but improving result reception is more difficult. Risk calculation reorders the importance of quality monitors by balancing three probabilities: defect frequency, weight of potential harm, and detection difficulty. The triple approach of (1) a more focused suite of generic consensus quality indicators, (2) more active clinical laboratory testing stewardship, and (3) integration of formal risk assessment, rather than competing with economic value, enhances it.

How well do general practitioners manage laboratory test results for patients with diabetes mellitus and cardiovascular disease?: A systematic review.

PURPOSE: To evaluate how well general practitioners (GPs) manage and respond to laboratory results for patients with diabetes mellitus (DM) and cardiovascular disease (CVD). DATA SOURCES: MEDLINE, CINAHL, Embase, EBM reviews, ProQuest and Scopus. STUDY SELECTION: Peer-reviewed journal articles published between 2000 and 2015 that assessed GPs' management of laboratory results for patients with DM or CVD. DATA EXTRACTION: Study design and demographics, laboratory tests and key findings relating to GP management of laboratory results were extracted from studies. RESULTS OF DATA SYNTHESIS: Thirteen articles were included, comprising seven studies which utilized surveys, four observational studies, one cohort study and one randomized controlled trial. Findings indicate that GPs often overestimate the risk of complications associated with DM and CVD based on laboratory results and have unrealistically high expectations regarding the precision of laboratory tests. Considerable variation existed in the use of repeat testing for diagnostic confirmation and in GPs' identification of the difference between two consecutive results required to indicate a change in patient condition. GPs also often failed to initiate appropriate treatment for patients with DM and CVD based on laboratory results. Feedback to GPs about their test ordering patterns and educational messages on laboratory results improved clinical outcomes. CONCLUSION: Evidence about how well GPs manage results and its impact on patient outcomes remains weak and inconclusive. This review identified a number of areas where interventions could support GPs to improve the interpretation and management of laboratory test results, including feedback to GPs and educational messages on test result reports.

Diagnostic laboratories in Asia Pacific region: Investigation on quality characteristics and time of reporting.

This is the result of a Survey of various aspects of quality, cost and speed in a large sample of diagnostic laboratories in the Asia Pacific region. It is the first of its type to be published and represents a snapshot of the current performance in a large number of diagnostic laboratories in a broad range of countries in the Asia Pacific region. This demonstrates that there are common issues facing all the laboratories surveyed but also common solutions using a Quality Systems approach which involves Accreditation, Customer responsiveness, greater use of IT, automation and Lean principles. The Survey provides data on some quality characteristics such as Turnaround Time (TAT) and quality improvement activities. It has been the case that some of the KPIs have improved over the course of the Surveys for example a reduction in the average TAT, and it might be that this occurred as a result of participation. Most laboratories have a target of 46-60min for STAT (Short Turnaround Time) on Clinical Chemistry and Immunoassay samples.

Current Methods of Haemolysis Detection and Reporting as a Source of Risk to Patient Safety: a Narrative Review.

AIM: Haemolysis has a major impact on patient safety as the need for a replacement specimen increases the risk of injury and infection, delays test results and extends the duration of hospital stays. Consistency of haemolysis detection and reporting can facilitate the generation of benchmark data used to develop quality practices to monitor and reduce this leading cause of pre-analytical laboratory error. This review aims to investigate current methods of haemolysis detection and reporting. METHOD: Due to known heterogeneity and immaturity of the research field, a scoping search was conducted using PUBMED, Embase, Medline and CINAHL. Articles published between 2000 and 2014 that reported haemolysis rates in specimens from the general population were included. RESULTS: Of the 50 studies that met the inclusion criteria, 20 detected haemolysis using the Haemolysis Index (HI), 19 by visual inspection and 13 by undefined methods. There was large intra-study variation in the plasma free haemoglobin level used to establish haemolysis (HI: mean±SD 846±795 mg/L, range 150-3000 mg/L; Visual: 850±436 mg/L, 500-3000 mg/L). Sixteen studies reported the analyte of interest, with only three studies reporting a haemoglobin level at which the specimen would be rejected. CONCLUSION: Despite haemolysis being a frequent and costly problem with a negative impact on patient care, there is poor consistency in haemolysis detection and reporting between studies. Improved consistency would facilitate the generation of benchmark data used to create quality practices to monitor and reduce this leading cause of pre-analytical laboratory error.

Role of external management consultants in health-care organizations implementing TQM.

The reliance of organizations on consultants generally is increasing. Although the efficacy of the use of consultants in implementing change programs has been questioned, there have been limited attempts to systematically analyze the contribution of consultants. This article reports observations on the use of consultants in health-care organizations implementing total quality management (TQM). The relationship between the use of external management consultants and successful TQM implementation is not simple. There appears to be a difference in the way consultants are used by the public and private sectors, with the private organizations forming long-term relationships with their consultants. The perceived value of consultants to the private organizations was higher. Consultants are not a substitute for leadership, and the success of outside consultants probably depends on the commitment of senior management. External management consultants appeared to be linked to the successful implementation of TQM. Further, despite the conventional wisdom to the contrary, some prepackaged programs may be beneficial for the introduction of TQM into an organization.