Speaker: Joanna Sheldon (UK)
Moderator: Tommaso Trenti (IT)

Date: 24^th September 2019 at 18:00

The importance of standardisation is only just being realised and addressed in autoantibody measurements.  Immunoglobulins have a high degree of molecular heterogeneity, there are subclasses of IgG and IgA, and the affinity and avidity of antigen-antibody binding can vary both between and within individuals.  An immune stimulus may generate a monoclonal, oligoclonal or polyclonal response and this pattern of response will vary between individuals and even within an individual over the disease course.  There are multiple methods available for autoantibody detection which will vary in their abilities to detect different types of immunoglobulins.  Finally, the antigen to which we are trying to measure antibodies is usually a protein with its own molecular heterogeneity which may also be influenced by the source of the antigens and the preparation process.  Considering these complexities, it is unsurprising that there is marked variation in autoantibody concentrations measured with different methods.  However, the increasing reliance on automated quantitative autoantibody results has made standardisation or harmonisation of these tests vital.  The IFCC through a working group and more recently a committee have been integral to investigating and producing certified materials for IgG anti myeloperoxidase (ERM-DA476/IFCC) and IgG anti proteinase 3 (ERM-DA483/IFCC) with values assigned in mg/L, traceable to ERM Da 470k/IFCC (the certified reference materials for IgG).  Evaluation of patient samples showed that use of these materials will give a significant reduction in the spread of the numerical results over different methods.  However, there was only 30% concordance between positivity and negativity of results when interpreted with respect to each methods reference ranges.  The introduction of certified reference material (CRM) will be the essential first step in standardisation of autoantibody testing and although it does not solve every issue, it should give us a point of reference to identify the other components of the methods that need to be harmonised before we can have comparability in autoantibody results.

Unmet clinical needs assessment for biomarker evaluation - a practical toolbox for Laboratory Medicine.

Registration is open (enter the course to register). 

How to enter the course?

The translation of promising biomarkers to clinical application is a critical opportunity for laboratory medicine; to provide information that enables clinicians to make better decisions about the care of their patients. The realisation of this goal is itself critically dependent on the appropriate evaluation of novel biomarkers for use in the clinical setting.

Inherent to this concept is consideration of the unmet clinical need that a laboratory test is aiming to address.  However, as testing guides downstream clinical interventions to improve patient outcomes, the link between testing and outcomes is often indirect. As such, a full mapping of the clinical care pathway to define the purpose and role of the laboratory test and importantly, the clinical management decisions that the test will inform, thus enables the unmet clinical need to be addressed and furthermore complemented by the anticipated impact on patient outcomes.

The corollary from this approach is the early specification of analytical and clinical performance criteria to subsequently evaluation studies in a cyclical manner, keeping the clinical care pathway and outcomes as the key drivers in the process. In doing so, biomarker development can be aligned to address existing gaps in clinical care and mitigate research waste and inappropriate utilisation of laboratory tests where clinical benefit is uncertain or at worst potentially harmful.

There is a major opportunity here for laboratory professionals to play a key role in the development and implementation of clinical care pathways for new and existing laboratory tests. Stakeholder involvement; working together to overcome the conventional silos across disciplines is paramount to drive the adoption of innovative tests with robust implementation planning, so that test results are available and acted upon in an appropriate and timely manner, with a strong link to clinical intervention and outcomes. To realise the value of laboratory medicine in this context, the EFLM Working Group for Test Evaluation (WG-TE) has developed a ‘practical toolbox’ providing a Test Evaluation Framework and Interactive Unmet Clinical Needs Checklist (hosted on the EFLM eLearning platform) to assist laboratories and other key stakeholders in clinical translational research, to undertake clinical needs assessment and clinical care pathway development.

Speaker: Stephen Church (BD) ; on behalf of the EFLM Working Group on the Preanalytical Phase (WG-PRE)

Recorded on 18^th September 2018 at 18:00 CET

Abstract:

Vascular Access (VA) is a routine procedure, conducted worldwide, with an estimated 60-90% of hospital inpatients expected to require an intra-venous catheter (Helm et al., 2015), particularly in emergency situations or departments.  A number of vascular access devices (VADs) or IV catheters could potentially be used to collect blood samples, including peripherally-inserted venous catheters, centrally-inserted venous catheters and arterial catheters.  Practices and procedures for blood collection from conventional blood collection needles are well defined (Simundic et al., 2018).  Until recently, many guidelines have not commented on or proposed a best practice for collection from a VAD. The CLSI document GP41-A6 (2007) stated that without complete, thorough and documented training, “Phlebotomists should not draw blood from VADs.”  However the 2017 edition, GP41-A7, is the first to make recommendations for blood collection using VADs.  Trauma from VAD insertion, together with a tortuous blood path with increased shear forces, can contribute to increased cell lysis.  Further incomplete flushing of the collection site resulting in contamination and/or dilution of the specimen has the significant potential to create test errors and inaccurate results. While haemolysis is the most widely reported error (Lippi et al., 2011), impacts on coagulation parameters have also been reported (Strauss et al., 2012).  Furthermore, the collection may lead to dislodgement of the catheter and require a replacement.  In special circumstances, for example when obtaining samples from paediatric patients, adults with difficult venous access, presence of bleeding disorders or when serial tests are requested, blood collection from a short peripheral catheter may be clinically beneficial. In these patients, guidance on the best practice is required to ensure patient safety and care. 

This webinar will overview the risks associated with blood collections from VADs, the type of VAD from which samples may be collected and also provide recommendations on best practices to obtain the highest quality sample and ensure patient care.

Presenter: Federica Braga (IT)
Moderator: Anne Stavelin (NO)

Recorded on 17^th April 2018

The participation to EQA schemes that meet specific metrological criteria is mandatory for the evaluation of performance of participating laboratories in terms of standardization and clinical suitability of their measurements. The requirements for this type of EQA are as follows: in addition to the use of commutable control materials, it is necessary to assign values (and uncertainty) to them with reference measurement procedures (RMP) performed by an accredited laboratory and to define and apply clinically allowable performance specifications to verify the suitability of laboratory measurements in a clinical setting. Unfortunately, there are few permanent EQA programs covering these requirements because some practical constraints including technical, psychological and economic aspects, which limit their introduction. It is, however, clear that these aspects should be immediately solved. Indeed, EQA schemes are in a unique position to add substantial value to the practice of Laboratory Medicine, by identifying analytes that need improved harmonization and by stimulating and sustaining standardization initiatives that are needed to support clinical practice guidelines. This will definitively help those manufacturers that produce superior products to demonstrate the superiority of those products and oblige users (and consequently industry) to abandon assays with demonstrated insufficient quality.

Speaker: J.F.M. (Hans) Jacobs (NL)

Moderator: Christopher McCudden (CA)

Recorded on  27^th March 2018 at 14:00 CET

Treatment of multiple myeloma (MM) has substantially changed with the recent introduction of therapeutic monoclonal antibodies (mAb) which have further improved the rates and depth of clinical response. mAb therapy in MM patients has introduced new challenges in how therapy responses can be defined. On the one hand, recently approved mAb interfere with routine M-protein diagnostics. On the other hand, given the high rates of complete responses, new response categories need to be defined to measure minimal residual disease. As a reaction to these challenges research has focused on adaptations of conventional M-protein diagnostics to mitigate interference and on the introduction of novel methods that enable the identification of minimal residual disease. The aim of this e-seminar is to discuss how mAb therapy has changed both the therapeutic as well as the diagnostic landscape of MM. 

Speaker: Callum G. Fraser (UK)
Moderator: Sally C Benton (UK)

Date: 23^rd January 2018 at h. 18.00 CET

Registration is open (enter the course to register).

How to enter the course?

Abstract: Colorectal cancer (CRC) is still a very important health problem world-wide.  It is the third most common cancer and the fourth leading cause of cancer-related death. Fortunately, many screening programmes have now been set up to detect neoplasia in those who do not have any symptoms of bowel disease. These programmes lead to early detection of CRC and its precursors, which significantly improves outcomes.  There are a number of strategies available for CRC screening, but faecal immunochemical test for haemoglobin (FIT) are now considered as the best currently available non-invasive investigation and are being widely established.  FIT are available in two formats, qualitative FIT and quantitative FIT: the former are often used in opportunistic screening, whereas the latter are widely used in population-based programmatic screening. Quantitative FIT have many advantages, a major benefit being that the faecal haemoglobin concentration (f-Hb) can be estimated. This Webinar will explore the diagnostic accuracy of FIT, and factors affecting f-Hb, including age, sex and socioeconomic status.  The difficulties in selecting the f-Hb cut-off to be used for CRC screening will be addressed in detail.  

Speaker: Ana-Maria Simundic (HR)
Moderator: João Tiago Guimarães (PT)

Recorded on 21^st November 2017 at 18:00 CET

European National Societies, members of EFLM, have agreed in Porto, during the 3rd EFLM-BD European Preanalytical Phase Conference that harmonization of preanalytical practices and policies is necessary and possible in each and every country in Europe as well as internationally, at the European level. The Working group for Preanalytical phase (WG-PRE) of the European Federation for Clinical Chemistry and Laboratory Medicine (EFLM), has taken the leading role in this process. The aim of this e-seminar is to present past, ongoing and future WG-PRE activities and various projects which aim is to improve the quality of preanalytical phase in Europe as well as to promote wide harmonization of preanalytical practices, patient safety improvement and reduction of unnecessary waste and healthcare expenses.

Webinar recording + quiz.

Speaker: Ralf Lichtinghagen (GER)

Moderator: Merve Sibel Gungoren (TR)

Recorded at 18^th October 2017

The stage of fibrosis is the most important single predictor of significant morbidity and mortality in chronic liver disease. The mechanisms leading to fibrosis and eventually cirrhosis are thought to be similar, irrespective of the underlying etiology. At cellular level, hepatic stellate cells (HSC) undergo a phenotypic switch usually addressed as transactivation. Activated HSC are regarded as the main source of extracellular matrix (ECM) in the fibrotic liver. Additional cell types namely fibroblasts and myofibroblasts may also contribute to ECM deposition. Despite the similarities in pathophysiology at cellular level, morphogenesis and histologic appearance of the fibrotic liver may differ according to the etiology.

Liver biopsy remains the gold standard to evaluate liver fibrosis. Not least, one has to keep in mind that liver biopsy provides additional information like histological grading and etiology that may be overlooked when surrogate markers are used. Ideally, those tests should answer two questions. 1) What is the stage of fibrotic organ damage (i.e. the amount of deposited ECM and the disturbed balance of hepatic microarchitecture)? 2) What is the net balance between ECM deposition and degradation (i.e. the dynamics of ECM turnover)? The former serves to evaluate the prognosis and indicate therapy, while the latter might be used to control the efficacy of treatment with regard to disease progression.

Many different parameters including standard clinical chemistry and parameters of matrix metabolism have been evaluated. In the last decade, markers were assembled to multiparametric scores. Here, we can distinguish scores assembled of standard clinical chemistry markers (e.g. aspartate aminotransferase-to-platelet ratio index, FibroTest, Forns’ index) from scores using circulating markers of hepatic matrix metabolism like hyaluronic acid (HA), tissue inhibitor of metalloproteinases-1 (TIMP-1), matrix metalloproteinase-2, propeptide of type III procollagen (PIIINP).

In the webinar we will learn further details about the relevant complex scores, the clinical evaluation and current practical guidelines.

Biomarkers that are surrogates for cardiac pathophysiology may help us understand the "state of the heart" in heart failure and may be indications for certain treatments. A good biomarker will also be able to be monitored and a change in the level will reflect a change in the condition. I will speak of three biomarkers that do exactly this (natriuretic peptides, high sensitivity troponins and sST2). Natriuretic peptides (NPs) (BNP and NTproBNP) are guideline standards to confirm the diagnosis of heart failure. They are good for monitoring volume as we diurese the patient. Their weaknesses include wide variability in levels in a given patient as well as elevations not secondary to an increase in left sided filling pressures. Additionally, their value is questionable in patients receiving Entresto (a drug that inhibits breakdown of NPs). High sensitivity troponin in the setting of acute heart failure (and maybe chronic) represents subendocardial necrosis and has a bad prognosis. It is possible that drugs like nitrates will be used in heart failure treatment more commonly when levels of high sensitivity troponin are high. Finally, sST2 is a marker of fibrosis and is elevated in virtually all patients with heart failure. In the acute setting, it defines a "sicker" patient who needs advanced treatment to avoid re-hospitalization. In the chronic setting, titrating medication to a sST2 level below 35 ng/ml appears to mitigate risk, even in the setting of a continued high NP level. Data with Entresto suggest sST2 levels are going to be useful in both selection of patients for Entresto as well as monitoring treatment and maybe regulating the dose.

The estimate of measurement uncertainty is important in Laboratory Medicine because it is required for reference measurement laboratories to obtain/maintain the accreditation according to ISO 17025:2003 and ISO 15195:2005 and for clinical laboratories to obtain the accreditation according to ISO 15189:2012. There are two approaches to estimate measurement uncertainty, the so-called ‘bottom-up’ and ‘top-down’ approaches.

E-learning offers a broad variety of tools that can bridge information gap between these worlds. In this interactive webinar, we will cover following objectives:

• overview of basic tools used in e-learning
• familiarize attendants with 5 commonly used ways of delivering content by e-learning (webinar, voice-over presentation, quiz, user generated content + social media, e-book)
• give examples and practical hints for creating attractive educational materials

2nd EFLM Strategic Conference in Mannheim

Handling disruption of Laboratory Medicine in digital health

• the impact that the on-going digitalization of technologies and a digitalized society on the medical laboratory in future health care
  
• changing our capabilities to compile, integrate and visualize complex diagnostic data
• providing the opportunity for radical changes to diagnostic health strategies.
  

With the digital revolution spreading into every realm of modern medicine, we will experience a democratisation of health care, i.e. a comprehensive data usage not just being in the hands of health care professionals, but also in the patients´. Indeed, a central concept of digital health medicine is patient empowerment as demonstrated by key words like “electronic health record”, “patient access”, “health apps”, “wearable health tech” etc. In this rapidly changing health care environment, Laboratory Medicine must redefi ne its positions, not only acting in its classical role as provider of laboratory results, but also adopting new roles and responsibilities in the clinical dialogue.

Recorded on 18-19 June 2018.

The course will provide an overview of different models to set performance specifications in laboratory medicine; 1) based on clinical outcome, on 2) biological variation, and 3) state of the art. In addition, it will address the total error concept, and performance specifications in external quality assessment schemes and in the extra-analytical phases.

A recording of a plenary presentation by professor Mauro Panteghini, recorded at 4^th Joint EFLM-UEMS Congress: Warsaw, Poland, 21–24 September, 2016

Harmonization in laboratory testing is more than merely analytical harmonization. Although the focus was mainly on the standardization and harmonization of measurement procedures and their results, the scope of harmonization goes beyond method and analytical results. It includes all aspects of the total examination process from the “pre-pre-analytical” phase through analysis to the “post-post-analytical” phase. Rapidly available and precise results can indeed be of very limited value if they cannot be compared with each other, are produced on a wrong material or within an inappropriate diagnostic workflow. In particular, as evidence collected in last decades demonstrates that pre-pre- and post-post-analytical steps are more vulnerable to errors, harmonization initiatives should be performed to improve procedures and processes at the laboratory–clinical interface. Managing upstream demand, down-stream interpretation of laboratory results, and subsequent appropriate action through close relationships between laboratorians and clinicians remains a crucial issue of the laboratory testing process. Therefore, initiatives to improve test demand management from one hand and to harmonize procedures to improve physicians’ acknowledgment of laboratory data and their interpretation from the other hand are needed in order to assure quality and safety in the total examination process. A harmonized context will increase the value of laboratory results facilitating their interpretation and thus improving the patient’s outcome.

Tutorials serving for WG-DE activities.