External quality assessment-based tumor marker harmonization simulation; insights in achievable harmonization for CA 15-3 and CEA.

Objectives: CA 15-3 and CEA are tumor markers used in routine clinical care for breast cancer and colorectal cancer, among others. Current measurement procedures (MP) for these tumor markers are considered to be insufficiently harmonized. This study investigated the achievable harmonization for CA 15-3 and CEA by using an simulation of external quality assessment (EQA) data from multiple EQA programs using patient-pool based samples.

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.

Recommendations for validation testing of home pregnancy tests (HPTs) in Europe.

Home pregnancy tests (HPTs) available in Europe include accuracy and other performance claims listed on their packaging. Due to the lack of guidance on the standardisation of such products, it is often difficult to replicate these claims when tested on a clinical sample, whether in a laboratory setting or by lay users. The Diagnostic Regulation is a set of requirements that mandate comprehensive validation data on human pregnancy tests and other devices.

Perspective and priorities for improvement of parathyroid hormone (PTH) measurement - A view from the IFCC Working Group for PTH.

Parathyroid hormone (PTH) measurement in serum or plasma is a necessary tool for the exploration of calcium/phosphate disorders, and is widely used as a surrogate marker to assess skeletal and mineral disorders associated with chronic kidney disease (CKD), referred to as CKD-bone mineral disorders (CKD-MBD). CKD currently affects >10% of the adult population in the United States and represents a major health issue worldwide. Disturbances in mineral metabolism and fractures in CKD patients are associated with increased morbidity and mortality.

Standardization of tumor markers - priorities identified through external quality assessment.

Tumor markers are often heterogeneous substances that may be present in elevated concentrations in the serum of cancer patients. Typically measured by immunoassay, they contribute to clinical management, particularly in screening, case-finding, prognostic assessment, and post-treatment monitoring. Data both from external quality assessment (EQA) schemes and clinical studies demonstrate significant variation in tumor marker results obtained for the same specimen using different methods.

Alpha-Fetoprotein Detection of Hepatocellular Carcinoma Leads to a Standardized Analysis of Dynamic AFP to Improve Screening Based Detection.

Detection of hepatocellular carcinoma (HCC) through screening can improve outcomes. However, HCC surveillance remains costly, cumbersome and suboptimal. We tested whether and how serum Alpha-Fetoprotein (AFP) should be used in HCC surveillance.

Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer: Updated Guidelines From the European Group on Tumor Markers.

Objective: To present an update of the European Group on Tumor Markers guidelines for serum markers in epithelial ovarian cancer.

Methods: Systematic literature survey from 2008 to 2013. The articles were evaluated by level of evidence and strength of recommendation.

Validation of new cancer biomarkers: a position statement from the European group on tumor markers.

Background: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use.

Content: In this review, we discuss the key steps in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application.

Pregnancy testing with hCG--future prospects.

Pregnancy tests for human chorionic gonadotrophin (hCG) are used widely in hospital and home settings. Assays measuring hCG also have uses in prenatal screening and oncology. The output from three recent international workshops provides a framework for reliable measurement of hCG.

The harmonisation of growth hormone measurements: taking the next steps.

For over 20 years differences in results of growth hormone (GH) measurement have been recognised as being significant enough to lead to misdiagnosis and inappropriate management of patients with GH-related disorders. Whilst issues of method standardisation, variable antibody specificity, use of different reporting units with different conversion factors, and interference from GH binding protein have been acknowledged as contributing to the discrepancies, inconsistent approaches to method harmonisation have hampered opportunities to enhance the evidence base for GH measurements. Amongst the first steps to be taken, international collaboratives recommended the universal adoption of the International Standard 98/547 and the reporting of results in mass units.

Common decision limits --The need for harmonised immunoassays.

The main aim of clinical guidelines is to encourage the best clinical outcome for patients and the best use of resources, no matter where patients are investigated or managed. Where guidelines incorporate decision limits based on levels of analytes in serum, plasma or urine these may determine whether or not to treat or may be used to tailor further treatment. Consideration should be given to the effect of method-related differences in results when implementing common decision limits.

External quality assessment of hormone determinations.

Hormone determinations are of central importance to the practice of Clinical Endocrinology, and ensuring their correct use and performance is a multidisciplinary responsibility involving clinicians, laboratory staff, manufacturers of diagnostic systems and healthcare regulatory agencies. All these professional groups have, therefore, an interest in external quality assessment (EQA) as an audit tool that can identify areas where use of tests in routine practice requires improvement to reduce risks to patients. This chapter reviews the principles of EQA, and outlines its strengths and limitations, illustrated with example data from the UK National External Quality Assessment Service (UK NEQAS).

Sampling and storage conditions influencing the measurement of parathyroid hormone in blood samples: a systematic review.

Parathyroid hormone (PTH) is relatively unstable: optimisation of pre-analytical conditions, including specimen type, sampling time and storage conditions, is essential. We have undertaken a systematic review of these pre-analytical conditions. An electronic search of the PubMed, Embase, Cochrane, Centre for Research and Dissemination and Bandolier databases was undertaken.

External quality assessment schemes for immunoassays.

External quality assessment schemes (EQAS) provide an important means of monitoring the quality of the performance of immunoassays in the field. Set up by external bodies and complementing internal quality control procedures, they enable ongoing comparison of individual laboratory results, both with independently established target values and with results of other participating laboratories. Well-designed EQAS assess analytical performance particularly with respect to bias and precision, but also give some indication of the type of errors that most frequently occur in routine practice.

A comparison of the analytical performance of five commercially available assays for neutrophil gelatinase-associated lipocalin using urine.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker for acute kidney injury that is beginning to be used in clinical practice in addition to research studies. The current study describes an independent validation and comparison of five commercially available NGAL assays, focusing on urine samples. This is an essential step in the translation of this marker to clinical use in terms of allowing valid inter-study comparison and generation of robust results.

Gaps in the traceability chain of human growth hormone measurements.

Background: Human growth hormone (hGH) is measured for the diagnosis of secretion disorders. These measurements fall under the EU Directive 98/79/EC on in vitro diagnostic medical devices requiring traceability of commercial calibrator values to higher-order reference materials or procedures (Off J Eur Communities 1998 Dec 7;L 331:1-37). External quality assessment schemes show large discrepancies between results from different methods, even though most methods provide results traceable to the recommended International Standard (IS 98/574).

Design of tumor biomarker-monitoring trials: a proposal by the European Group on Tumor Markers.

A major application of tumor biomarkers is in serial monitoring of cancer patients, but there are no published guidelines on how to evaluate biomarkers for this purpose. The European Group on Tumor Markers has convened a multidisciplinary panel of scientists to develop guidance on the design of such monitoring trials. The panel proposes a 4-phase model for biomarker-monitoring trials analogous to that in use for the investigation of new drugs.

Variation in parathyroid hormone immunoassay results--a critical governance issue in the management of chronic kidney disease.

Renal physicians strive to maintain parathyroid hormone (PTH) concentrations for patients with chronic kidney disease (CKD) within guideline limits, but poor method comparability means there is currently serious risk of clinical misclassification. The potential for under- or over-treatment is significant, representing a major challenge to patient safety. In the short-term, raising awareness of clinical implications of method-related differences in PTH is essential.

Analytical error and interference in immunoassay: minimizing risk.

Although generally robust, immunoassays remain vulnerable to occasional analytical errors that may have serious implications for patient care. Sporadic errors that occur as a result of properties of the specimen are particularly difficult to detect. They may be due to the presence of cross-reacting substances, antianalyte antibodies or antireagent antibodies, all of which may lead to erroneously high or low results.

The National Institute for Health and Clinical Excellence (NICE) guidelines for early detection of ovarian cancer: the pivotal role of the clinical laboratory.

The National Institute for Health and Clinical Excellence (NICE) has recently reviewed optimal means of early recognition and initial management of ovarian cancer, the leading cause of gynaecological death in the UK. The NICE guidelines state that general practitioners should measure serum CA125 in women presenting with persistent and continuous symptoms suggestive of ovarian cancer (e.g.

Roadmap for harmonization of clinical laboratory measurement procedures.

Results between different clinical laboratory measurement procedures (CLMP) should be equivalent, within clinically meaningful limits, to enable optimal use of clinical guidelines for disease diagnosis and patient management. When laboratory test results are neither standardized nor harmonized, a different numeric result may be obtained for the same clinical sample. Unfortunately, some guidelines are based on test results from a specific laboratory measurement procedure without consideration of the possibility or likelihood of differences between various procedures.

Taking a new biomarker into routine use--a perspective from the routine clinical biochemistry laboratory.

There is increasing pressure to provide cost-effective healthcare based on "best practice." Consequently, new biomarkers are only likely to be introduced into routine clinical biochemistry departments if they are supported by a strong evidence base and if the results will improve patient management and outcome. This requires convincing evidence of the benefits of introducing the new test, ideally reflected in fewer hospital admissions, fewer additional investigations and/or fewer clinic visits.

Perspectives in Clinical Proteomics Conference: translating clinical proteomics into clinical practice.

Although there have been numerous publications on biomarkers, few new tests have been adopted in routine clinical practice. The major purpose of the very interesting multidisciplinary Perspectives in Clinical Proteomics Conference, which was convened under the auspices of the Wellcome Trust at the Wellcome Trust Genome Campus near Cambridge, was to explore reasons for this. Established and emerging proteomic markers in conditions ranging from kidney disease to neurochemical dementia were reviewed on the first day, while presentations on the second day specifically addressed the all-important question, "What does it take to translate a biomarker into clinical use?" More than 70 participants representing 60 organizations, nine countries and varied backgrounds convened in the tranquil surroundings of the Wellcome Trust Genome Campus for this truly multidisciplinary conference.