40 years external quality assessment--what have we achieved? A personal view.

The present report deals with a personal interaction with different external quality assessment (EQA) programmes over the past four decades for different groups of analytes. The effects of national and international legislation and standardization, as well as certification and accreditation standards have also been taken into account. The effects and limitations of reference method procedures and reference materials are also discussed as are the trends in accuracy and precision, the latter especially in terms of automation and decentralization of laboratory analyses.

An educational web-based external quality assessment outcome and evaluation: first experiences with urinary sediment and hemostaseology.

External quality assessment is a standard procedure for many medical laboratories, especially those accredited according to ISO 15189. INSTAND has developed web-based quality control surveys (WQ) with integrated case-based learning in collaboration with the Institute for Teaching and Educational Research in Health Sciences (IDBG), University of Witten/Herdecke. The WQs were presented via a weblink using the learning management system CASUS.

Experience with an alternative form of samples for external quality assessment of urinary sediment (visual sample EQA).

Background: Urinary sediment components are mainly unstable, especially in their original forms. This makes the use of such material in routine external quality assessment surveys (EQAS) almost impossible. The development of an alternative EQAS for urinary sediment using photomicrographs (visual-sample EQAS) is described here, together with results, improvements and future plans.

The determination of uric acid in urine--forgotten problems rediscovered in an external quality assessment scheme.

This article mainly describes the effects of boric acid and borates often used as bacteriostatic agents in urine collection for microbiological examination, on the results obtained in the measurement of uric acid in urine using the uricase [EC.1.7.

Has the introduction of the European Parliament Directive 98/79/EC from 1998-10-27--concerning in-vitro diagnostic devices (IVD-directive) influenced performance of hormone immunoassay kits in terms of precision and accuracy? Results from selected external quality assessment (EQA) schemes between 1993 and 2008.

The aim of this report is to examine what--if any--effects the introduction of the European Directive 98/79/EC has had on the performance of in-vitro diagnostic devices (kits) used in determining hormones and related measurands in medical diagnostic laboratories. The observations covered the period from 1993-2008, results being taken from EQA surveys at three year intervals. The measurands chosen were: cortisol, progesterone, testosterone, 17beta oestradiol (E2), free triiodothyronine (fT3), total triiodothyronine (TT3), free thyroxine (fT4), total thyroxine (TT4), thyrotropin (TSH), luteotropin (LH), follitropin (FSH), prolactin (PRL), parathyrin (PTH), thyroglobulin (Tg), anti-thyroid microsomes (MAb), anti-thyroid peroxidase (Anti-TPO), anti-thyroglobulin (Anti-Tg) and anti-TSH-receptor (TRAb).

Immunoassays & co.: past, present, future?--A review and outlook from personal experience and involvement over the past 35 years.

This article has been designed to give a brief overview of antigen-antibody reactions, especially in the form used in immunoassays. The different types of label and assay design have been described briefly. The report has not been designed as a brief text book, so that diagrams referring to assay principles have been omitted.

Comparison of performance of classical clinical chemistry analysers with test-strip devices (Reflotron) and those based on film technology (Vitros) in external quality assessment (EQA) surveys.

This article reports on the performance of two "dry" chemistry devices, (Reflotron, Roche Diagnostics and Vitros, Johnson & Johnson) and compared them with classical "wet" chemistry analysers in four commercially produced quality assessment samples (Roche PNU and PPU and Seronorm Human and Human High Controls) sent repeatedly over a 12-month observation period. Eleven analytes (including five enzymes) were studied, eight of which had target values set by reference method procedures. The results showed that both devices gave comparative results for the same sample sent in different EQA-surveys.

The alkaline haematin detergent (AHD575) method for the determination of haemoglobin in blood--a candidate reference measurement procedure.

The article describes the development and evaluation of the alkaline haematin detergent (AHD575) method for the determination of haemoglobin in blood without the need for toxic materials and suitable for use in laboratories in countries with limited resources and restricted import of toxic materials. The validation of the method has been performed in accordance with the requirements set out in the international standard ISO 15193, which describes the procedures necessary for development of a candidate reference measure-ment procedure. The main results were: The trueness of the haemiglobin cyanide (HiCN) method depends upon the diluent used.

Sample commutability in external quality assessment surveys (EQAS) for thyroid-related antibodies--state of the art.

External quality assessment surveys for thyroid-related antibodies have been offered by INSTAND for 20 years. During this time, some problems have remained, especially those between the similarity of samples sent and routine patient samples. Here the questions of "matrix effects" and "commutability of results" are topics discussed at most EQA-meetings.

Practical solution for control of the pre-analytical phase in decentralized clinical laboratories for meeting the requirements of the medical laboratory accreditation standard DIN EN ISO 15189.

This report was written in response to the article by Wood published recently in this journal. It describes a practical solution to the problems of controlling the pre-analytical phase in the clinical diagnostic laboratory. As an indicator of quality in the pre-analytical phase of sample processing, a target analyte was chosen which is sensitive to delay in centrifugation and/or analysis.

Problems and practical solutions in the external quality control of point of care devices with respect to the measurement of blood glucose.

Point of care testing (POCT) is evolving at an ever increasing rate. This article deals mainly with the aspect of POCT for blood glucose and the problems of external quality assessment (EQA) of point of care devices (POCD). At the present time it is only possible to control precision with EQA, independent of the matrix of the test materials (synthetic polymer-base, plasma/serum, or processed whole blood).

Problems with the external quality assessment of accuracy of point of care devices (POCD) for blood glucose are independent of sample composition.

This short article describes the results obtained in both internal and external quality assessment of point of care devices (POCD) for the monitoring of blood glucose. The results show that the use of synthetic, serum and whole blood matrices for the samples do not markedly change the inaccuracy of measurement. It is only possible to check precision of POC devices for glucose in external quality assessment (EQA) surveys for POC devices for blood glucose.

A novel LC-IDMS/MS method for the determination of the cardiac glycosides digoxin and digitoxin using caesium adducts.

This article describes an essential improvement of the published candidate reference measurement procedure for digoxin and digitoxin and compares it with the original method. The novelty of the method lies in the measurement of the caesium (Cs+) ion as product ion in the multiple reaction monitoring mode (MRM) with potentially improved analytical specificity whilst retaining a comparable accuracy and precision at therapeutic levels. The original measurement procedure used the single-ion mode (SIM).

A new approach for the determination of immunosuppressive drugs using HPLC-MS/MS and Cs+ adducts.

In this study a new principle of measurement in LC-MS/MS (liquid chromatography mass spectrometry) for determination of the immunosuppressive drugs sirolimus, everolimus, tacrolimus, and cyclosporin A has been introduced by using the Cs(+) ion as the product ion in the multiple reaction monitoring mode (MRM). Separation of the immunosuppressive agents was achieved using a phenyl-hexyl-RP column together with a ternary gradient elution profile, consisting of water, methanol and acetonitrile combined with 0.1% v/v formic acid and 0.

The preanalytical phase--can the requirements of the DIN-EN-ISO 15189 be met practically for all laboratories? A view of the "German situation".

This article describes practical problems in carrying out witness audits in terms of the international normal ISO 15189, with special regard to the situation in medical diagnostic laboratories in Germany. The presence of central laboratories--for example in hospitals--and decentralised laboratories--usually in the private sector--present different problems, especially in terms of the preanalytical phase and its control during witness audits for laboratories accredited according to ISO 15189. Whereas the preanalytical phase can be--at least in theory--controlled completely in and by a centralised hospital laboratory, for example by the use of "sample-collection teams", the problems in preparation and transporting of samples from a peripheral practice to a decentralised analytical laboratory cannot be fully controlled.

Some practical thoughts on restructuring the current guideline of the Federal Medical Council (Richtlinie der Bundesärztekammer [RiliBAK]) in Germany for quality control of clinical laboratory analyses based on results from external quality assessment surveys.

The present article presents a critical review of the current guidelines of the Federal Medical Council (Richtlinie der Bundesärztekammer--[RiliBAK]) in Germany, both for internal and external quality control. Examples have been chosen for analytes which present problems. These include thyrotropin (TSH) and human chorionic gonadotropin (hCG).

External quality assessment of tumour marker analysis: state of the art and consequences for estimating diagnostic sensitivity and specificity.

This review shows the current analytical quality for the following analytes used as tumour markers in the external quality assessment (EQA)-programmes of Instand e.V., a national EQA-organiser in Germany: Corticotropin (ACTH), growth hormone (GH, hGH), prolactin (PRL), chorionic gonadotropin (CG, hCG), calcitonin (CT, hCT), thyroglobulin (Tg), carcinoembryonic antigen (CEA), CA-Antigens 125, 72-4, 15-3 and 19-9, alpha foetoprotein (AFP) and prostate-specific antigen (PSA).

Establishment of reference intervals for enzyme catalytic activity concentration measurements at 37 degrees C--a practical approach.

The change from measuring enzyme catalytic activity concentrations from 25 degrees C to 37 degrees C in the German Federal Republic has led to the need for new reference ranges for defined patient groups and for healthy individuals. Up to now, these are only present as tentative values and are incomplete, especially for children. This article describes a method for deriving reference ranges from results obtained from measurement at 25 degrees C and 37 degrees C and the use of percentiles to establish values for 37 degrees C.

Comparability of method results and performance in a national external quality assessment scheme between 1993 and 2003 using thyroid associated analytes as examples.

Six thyroid analytes (free and total triiodothyronine and thyroxine, thyrotropin and thyroglobulin) have been followed up over a 10 year period in a national external quality assessment scheme (EQAS) organised by the Institute for Standardisation and Documentation in the Medical Laboratory (INSTAND). I. The following points were observed: II.

Comparability of method results and performance in a national external quality assessment scheme between 1993 and 2003 using thyroid associated antibodies as examples.

Four thyroid antibodies (antibodies to microsomes [MAb], thyroid peroxidase [anti-TPO], thyroglobulin [anti-Tg] and TSH-receptor [TRAB, THYBIA]) have been followed up over a 10-year period in a national external quality assessment scheme (EQAS) organised by the Institute for Standardisation and Documentation in the Medical Laboratory (INSTAND e.V.).

Determination of the cardiac glycosides digoxin and digitoxin by liquid chromatography combined with isotope-dilution mass spectrometry (LC-IDMS)--a candidate reference measurement procedure.

This article describes a method of high analytical sensitivity, reproducibility and trueness for the determination of digoxin and digitoxin in serum or plasma at therapeutic levels using a combination of high-pressure liquid chromatography (HPLC), isotope-dilution mass spectrometry (IDMS) and caesium-adduct formation. A method for threefold deuterium substitution in the glycosides was developed, which could be performed within 24 hours without distillation giving yields > 98% of the theoretical value. Extraction from a serum or plasma matrix was performed using a liquid-phase extraction with ammonium acetate buffer/tertiary butylmethyl ether/ethyl acetate at pH 9.

Experience with an external quality assessment programme for point-of-care-testing (POCT) devices for the determination of blood glucose.

This article describes the preparation and internal and external evaluation of materials, critical issues in the external quality assessment (EQA) of point-of-care testing (POCT) devices for measuring blood glucose. A comparison was made between different materials, both of natural and synthetic origin and with and without stabilisers. The aims were to produce a material which was compatible with as many POCT-devices as possible and so reduce the number of materials sent out in each campaign as well as to optimise the precision and comparability of results between methods and devices.

How to make things work again--troubleshooting using the GC-IDMS determination of triacylglycerols as an example.

This article describes the process of "repairing" a method which has gone out of control, using the gas-chromatographic isotope-dilution mass spectrometric (GC-IDMS) determination of total glycerides in serum, measured as glycerol. The original method used 13C2-glycerol as aqueous internal standard and 12C-tripalmitin dissolved in toluene as external standard. The modified method used tripalmitin as internal and external standard, the former being labelled uniformly on the glycerol moiety of tripalmitin (13C3-tripalmitin).