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Laboratory medicine is amongst the fastest growing fields in medicine, crucial in diagnosis, support of prevention and in the monitoring of disease for individual patients and for the evaluation of treatment for populations of patients. Therefore, high quality and safety in laboratory testing has a prominent role in high-quality healthcare. Applied knowledge and competencies of professionals in laboratory medicine increases the clinical value of laboratory results by decreasing laboratory errors, increasing appropriate utilization of tests, and increasing cost effectiveness. This collective paper provides insights into how to validate the laboratory assays and assess the quality of methods. It is a synopsis of the lectures at the 15th European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Continuing Postgraduate Course in Clinical Chemistry and Laboratory Medicine entitled "How to assess the quality of your method?" (Zagreb, Croatia, 24-25 October 2015). The leading topics to be discussed include who, what and when to do in validation/verification of methods, verification of imprecision and bias, verification of reference intervals, verification of qualitative test procedures, verification of blood collection systems, comparability of results among methods and analytical systems, limit of detection, limit of quantification and limit of decision, how to assess the measurement uncertainty, the optimal use of Internal Quality Control and External Quality Assessment data, Six Sigma metrics, performance specifications, as well as biological variation. This article, which continues the annual tradition of collective papers from the EFLM continuing postgraduate courses in clinical chemistry and laboratory medicine, aims to provide further contributions by discussing the quality of laboratory methods and measurements and, at the same time, to offer continuing professional development to the attendees.

Background: The interpretation of semi-quantitative methods has always been difficult, because the different kitmanufacturers use varying concentration values and there is a considerable overlap between kit-defined concentrations within the same kit (Kit: 'Ready-to-use' measuring system specific for each manufacturer's product)., Material: More than 2000 private practitioners and laboratories participated in three external quality control surveys on urine-glucose performed with a total of six control materials with known concentrations., Method: The ordinal scale model for evaluation of dichotomous methods based on rankit transformation of fractions of positive results (Petersen et al. Scand J Clin Lab Invest 2008;68:298-311) has been extended and modified to handle semi-quantitative data. Here, the percentages of results larger than the kit-concentration is calculated for each control sample and applied as a dichotomous method. Thereafter, these percentages are separated into all the defined kit-concentrations., Results: A total of eight kits had more than 50 measurements on at least four control materials which made them eligible for the calculations of logarithmic mean and standard deviation and thereby geometric mean and coefficient of variation for each of the kit-concentrations of each kit. Based on these parameters, the true concentration for selected percentages of each kit-concentration could be estimated. Moreover, the percentages of the different kit-concentrations could be calculated for each known true concentration., Conclusions: The present model is a powerful tool for improved characterization of semi-quantitative kits, which makes it possible to evaluate and validate kits and to optimize external quality control.

Blood smear analysis is a well-known technique in medical laboratories. The clinical relevance of this analysis and its interpretation are very important. Consequently, monitoring of laboratory performance by an external quality assessment scheme is strongly recommended. This article represents a very practical guidance document for External Quality Assessment Scheme (EQAS) organizers for setting up blood smear schemes. In the first part of the guidelines, the Hematology Working Group of the European External Committee for External Quality Assurance Programmes in Laboratory Medicine (EQALM) published practical information for the preparation of blood smears for use in an EQAS. Part II focuses on aspects such as survey preparation, statistical evaluation and reporting, and describes particular details for organizing blood morphology EQA surveys by means of virtual microscopy.

When communicating results from laboratory investigations from the laboratory to the requesters and further between different information systems, it is important that the value as well as the unique identity and name of the laboratory investigation are correctly cited. A committee under the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) and International Union for Pure and Applied Chemistry (IUPAC) has developed a systematic nomenclature for the correct classification of laboratory investigations. Each generic laboratory investigation is provided with a unique NPU code. The system is in use among approximately 30 different clinical laboratories in Sweden, and has capacity to be the common denominator of all laboratory investigations, and to be used as the identifier in various information systems. The NPU system for the Swedish laboratories is currently administered by EQUALIS and partly financed by the participating laboratories. Other ways of funding, of benefit for the whole health care sector, will be investigated.

In 2003, The National Academy of Clinical Biochemistry published a consensus monograph on thyroid tests (available via Internet from 2002). The document, a result of international collaboration, describes the pathophysiological background and clinical application of the measurements as well as principles for their technical performance. Of value, and of definite clinical relevance, is the detailed description of factors affecting the results in health and disease. However, we lack a description of the sometimes large differences in values obtained with different generally available methods, as well as a presentation of the occurrence and evaluation of analytical interference and related technical factors affecting results. Readers with little experience from quantitative measurement in the clinical laboratory, therefore, are not stimulated to obtain a better understanding of causes and evaluation of unexpected results.

Up to 136 laboratories participated in a joint effort to assess the trueness of routine measurements for 14 serum components. An unmodified, fresh-frozen human serum ("IMEP-17 Material 1"), produced for an international inter-laboratory comparison, served as the "master material". The serum had assigned values of the highest available metrological quality, and is assumed to involve no or negligible commutability problems. The material was used in the assignment of traceable values to two other reference sera, "CAL" and "X", through parallel measurements on the three materials according to a common protocol. In this transfer process, uncertainty estimates were provided for all values. The material CAL had been supplied with reference measurement procedure values in 1997, and the two sets of assigned values agreed well. A lyophilized control serum "HK02" was also included in the routine analysis series. It, too, had assigned values based on reference measurement procedures. Significant matrix effects were found. The project has provided: Assigned traceable values for 14 components in a fresh-frozen serum, available to Nordic laboratories for the coming years as "NFKK reference serum X"; Confirmation of earlier assigned reference measurement procedure values for a number of components in CAL, the main calibrator in the Nordic Reference Interval project (NORIP). The transferred values will now serve as the primary reference.; Evidence of long-term stability ( > or = 5 years) of the fresh-frozen serum CAL when stored at -80 degrees C; Evidence of substantial matrix effects in the processed serum HK02. The findings should be used to discuss to what extent reference measurement procedure values are useful and cost-efficient for this type of material.

Eight haematological quantities were measured in EDTA anticoagulated venous blood specimens collected from 1826 healthy male and female individuals between 18 and 90 years of age in the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden). The samples, collected between November 1999 and November 2001 as part of the Nordic Reference Interval Project (NORIP), were analysed on 12 different types of modern automated haematology instruments currently in use among the 60 laboratories participating in the study. Non-parametric reference intervals (between 2.5 and 97.5 percentiles) have been calculated for B-Haemoglobin (females 117-153 g/L, males 134-170 g/L), B-Erythrocytes (females 3.94-5.16 x 10(12)/L, males 4.25-5.71 x 10(12)/L), B-EVF (females 0.348-0.459, males 0.395-0.500), B-MCV (82-98 fL), Erc-MCH (27.1-33.3 pg), Erc-MCHC (317-357 g/L), B-Trc (females 165-387 x 10(9)/L, males 145 x 348 x 10(9)/L) and B-Lkc (3.5-8.8 x 10(9)/L). Partitioning of data according to age and gender was done according to a standardized procedure. For most variables the calculated reference intervals corresponded well with older and less well-defined reference intervals. The mean concentration of B-Haemoglobin increased by 0.08 g/L per year of age in women, and decreased by 0.1 g/L per year of age in men. B-Haemoglobin increased with body mass index in both men and women. Smoking increased the mean of B-Lkc by 1.1 x 10(9)/L and regular use of alcohol increased the mean of B-MCV by 0.8 fL. The influence of these factors was small overall and did not promote specific reference intervals.

Diagnosis of definite "Acute Myocardial Infarction" by the old WHO criteria depends on the diagnostic sensitivity and specificity of the biochemical marker used. Troponins have higher diagnostic sensitivity and specificity than the current "gold standard" for AMI, CK MBmass. Troponin T (TnT) provides both diagnostic and prognostic information on Minor Myocardial Damage (MMD) even in patients without increases of CK MBmass. Consequently, we evaluated the possibility of replacing CK MBmass with TnT. We first re-evaluated a previous, well-documented material of 502 time series from AMI-suspected cases, 50% of which were primarily classified as AMI by CK MBmass > or = 10 micrograms/L. We found that a TnT discriminator limit of 0.40 microgram/L gave the same AMI prevalence. We then identified from our laboratory data base 1995-1998 acute patient episodes with > or = 3 pairs of CK MBmass and TnT. This resulted in 754 episodes with max CK MBmass > or = 10 micrograms/L (AMI), 93 episodes with maximal CK MBmass < 10 micrograms/L and TnT > or = 0.10 microgram/L (MMD), and 730 episodes with max concentrations below the discriminators of both markers (NOT-MMD). TnT > or = 0.40 microgram/L detected 91% of all AMI giving a posterior probability of "AMI" > 99%. The criterion: "maximal TnT within the interval 0.10-0.40 microgram/L" detected 94% of all MMD and 9% of all AMI giving posterior probabilities about half MMD and half "small AMI", the latter characterized by less than 3-fold increased maximal CK MBmass. Thus, this TnT interval confirmed the gradual transition between MMD and small AMI. We suggest gradation of myocardial damage by TnT.