Multicentre evaluation of the Boehringer Mannheim/Hitachi 917 analysis system.

The new selective access analysis system BM/Hitachi 917 was evaluated in an international multicentre study, mainly according to the ECCLS protocol for the evaluation of analysers in clinical chemistry. Forty-three different analytes, covering 56 different methods--enzymes, substrates, electrolytes, specific proteins, drugs and urine applications--were tested in seven European clinical chemistry laboratories. Additionally, the practicability of the BM/ Hitachi 917 was tested according to a standardized questionnaire. Within-run CVs (median of 3 days) for enzymes, substrates and electrolytes were <2% except for creatine-kinase MB isoform and lipase at low concentration. For proteins, drugs and urine analytes the within-run CVs were < 4% except for digoxin and albumin in urine. Between-day median CVs were generally < 3% for enzymes, substrates and electrolytes, and < 6% for proteins, drugs and urine analytes, except for lipase, creatine kinase and MB isoform, D-dimer, glycosylated haemoglobin, rheumatoid factors, digoxin, digitoxin, theophylline and albumin in urine in some materials. Linearity was found according to the test specifications or better and there were no relevant effects seen in drift and carry-over testing. The interference results clearly show that also for the BM/Hitachi 917 interference exists sometimes, as could be expected because of the chemistries applied. It is a situation that can be found in equivalent analysers as well. The accuracy is acceptable regarding a 95-105% recovery in standard reference material, with the exception of the creatinine Jaffé method. Most of the 160 method comparisons showed acceptable agreement according to our criteria: enzymes, substrates, urine analytes deviation of slope +/- 5%, electrolytes +/- 3%, and proteins and drugs +/- 10%. The assessment of practicability for 14 groups of attributes resulted in a grading of one-three scores better for the BM/Hitachi 917 than the present laboratory situation. In conclusion, the results of the study showed good analytical performance and confirmed the usefulness of the system as a consolidated workstation in medium-sized to large clinical chemistry laboratories.

Analytical performance of Elecsys 2010--a multicentre evaluation.

The analytical performance of Elecsys 2010 has been assessed in a multicentre evaluation, which involved twelve laboratories from eight countries worldwide. Eleven alanytes (TSH, T4, FT4, T3, FT3, T-up, TNT, CK-MB, HCG, CEA and PSA) were tested using a protocol related to the ECCLS guidelines and the Standard Operating Procedures of the manufacturer. The evaluation was supported by a "Computer Aided Evaluation" (CAEv) program system and telecommunications. Within-run and between-day imprecision for the various analytes with 3% CV and 3 to 8% CV, resp. was comparable to homogeneous immunoassays e.g. for specific proteins on clinical chemistry analysers. The functional sensitivity for TSH, TNT and PSA was met by low concentrations: < 0.02 microIU/ml TSH, < 0.05 ng/ml TNT and < 0.07 ng/ml PSA. TSH is an assay of the third generation according to the recommendation of Spencer. The measured lower detection limit was less or equal to the manufacturer's specifications with the exception of the PSA assay. Drift effects (over eight hours) and signal carry-over effects were not observed. A high-dose hook effect became relevant for concentrations higher than 430,000 IU/HCG--an assay with a dynamic range of 10,000 IU/I. The Elecsys assays showed a high dynamic range and rarely necessary predilutions could be performed by the Elecsys instrument using the Elecsys multidiluent. Endogenous interferences were not observed. Calibration stability was confirmed for one week and data indicated that it could be extended at least for three weeks. The quality assurance experiment showed a good transferability of the results between the participating laboratories. The assigned values of two interlaboratory survey materials were found for most of the analytes within a deviation of +/- 10%. Higher deviations could be explained by differences in standardization and methods. The Elecsys 2010 system offers a high analytical sensitivity in combination with relatively low sample volumes and short measuring times (< or = 18 minutes); a high dynamic measuring range reduces the number of reruns and makes the work-flow more convenient. The electrochemiluninescence technology of Elecsys 2010 shows advantages in system performance without having any drawbacks compared to existing technologies.

Multicentre evaluation of the Boehringer Mannheim/Hitachi 911 Analysis System.

The analytical performance and practicability of the Boehringer Mannheim (BM)/Hitachi 911 analysis system have been assessed in a multicentre evaluation, which involved six laboratories from European countries. Analytes commonly used in classical clinical chemistry were tested in a core programme, which mainly followed the ECCLS guidelines. In addition, a satellite programme covered other analytes, such as proteins, drugs and urine analytes. In total, the study comprised more than 100 000 data items collected over a three-month period. The evaluation was supported with 'Computer Aided Evaluation' (CAEv) and telecommunications.Acceptance criteria for the results were established at the beginning of the study. Nearly all of the analytes met the imprecision limits: within-run imprecision (as CVs) was 2% for enzyme and substrate assays, 1% for ISE methods and 5% for immunoassays; between-day imprecision was 3l% for enzyme and substrate assays, 2% for ISE methods and 10% for immunoassays.No relevant drift effects (systematic deviation >/= 3%) were observed over eight hours. The methods were linear over a wide range. Sample-related and reagent-dependent carry-over can be reduced to a negligible amount by integration of a softwarecontrolled wash-step.Endogenous interferences were found for creatinine (Jaffé method) and uric acid assays (caused by bilirubin), for creatine kinase, creatine kinase MB isoform and gamma-glutamyltransferase (caused by haemoglobin), and for immunoglobulin A (caused by lipaemia)Accuracy was checked by an interlaboratory survey, recovery studies in control materials and method comparison studies. The survey showed that, with the exception of cholesterol and iron in two laboratories, the recovery of analytes did not deviate by more than 5%. Sixty-six of the 77 method comparisons performed met the acceptance criteria. The deviations of the remaining 11 results could be explained by differences in either calibration, application or by the use of different methods.Practicability was assessed using a questionnaire which covered all of the important aspects of an analysis system in the clinical laboratory. Twelve groups of attributes out of 14 were rater higher for the BM/Hitachi 911 than for the present situation in the laboratories concerned. Especially high scores were given for the versatility group.The acceptance criteria for the analytical performance of the BM/Hitachi 911 analysis system were fulfilled in all laboratory segments with few exceptions. The practicability exceeded the requirements in most of the attributes. The results of the study confirmed the usefulness of the system as a consolidated workstation in small- to medium-sized clinical laboratories and in STAT laboratories, or as an instrument for special analytes like proteins and drugs, or for urinalysis in large laboratories.

[Diagnosis of chronic pancreatitis. Studies of duodenal juice after stimulation with the secretin-ceruletide test. Decision limits and evaluation of various parameters]. / Diagnostik der chronischen Pankreatitis. Untersuchungen im Duodenalsaft nach Stimulation mittels Sekretin-Ceruletid-Test. Entscheidungsgrenzen und Bewertung verschiedener Messgrössen.

187 patients were checked up over 4 years by the secretin-ceruletide test. Independently of the test results they were assigned to various disease groups on the basis of clinical assessment. 131 subjects were divided in a pilot investigation into: subjects with a healthy pancreas (n = 55); subjects with chronic pancreatitis (n = 50); subjects whose pancreatic condition could not be classified clearly (n = 26). 8 parameters were compared by univariate and multivariate statistical procedures in order to confirm or rule out the presence of chronic pancreatitis. The discriminatory power of the following parameters in duodenal fluid proved to be sufficiently high, with less than 15% frequency of misclassification: chymotrypsin (activity) and/or; lipase (activity) and/or; amylase (activity); viscosity. Under routine conditions measurement of the activity of two of these enzymes is sufficient. Their contribution to discrimination proved to be approximately equal. The diagnostic sensitivity and specificity of the parameters bicarbonate, lipase (concentration), trypsin (activity) and volume of duodenal fluid are lower. The classification rules derived from the above pilot group were confirmed by a diagnostic study under routine condition in a test group of 38 patients. Limitation to examining only volume and a maximum of 3 parameters which proved best in distinguishing between patients with chronic pancreatitis and healthy subjects, together with the omission of the first-hour samples after a secretin bolus, considerably reduced laboratory workload without altering the discriminatory power of the secretin-ceruletide test.

CAEv-A program for computer aided evaluation.

The evaluation of new reagents and instruments in clinical chemistry leads to complex studies with large volumes of data, which are difficult to handle. This paper presents the design and development of a program that supports an evaluator in the definition of a study, the generation of data structures, communication with the instrument (analyser), online and offline data capture and in the processing of the results. The program is called CAEv, and it runs on a standard PC under MS-DOS. Version 1 of the program was tested in a multicentre instrument evaluation. The concept and the necessary hardware and software are discussed. In addition, requirements for instrument/host communication are given. The application of the laboratory part of CAEv is described from the user's point of view. The design of the program allows users a high degree of flexibility in defining their own standards with regard to study protocol, and/or experiments, without loss of performance. CAEv's main advantages are a pre-programmed study protocol, easy handling of large volumes of data, an immediate validation of the experimental results and the statistical evaluation of the data.

A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III.

The biometrical treatment of laboratory data may require the estimation of a regression line for the transformation of one set of measurements to another. The regression procedure introduced in part I (1) of our work does not always yield unbiased results in such situations, since its estimators are not scale invariant. In part III we present the parameter estimation of a general regression equation which is scale invariant and retains all properties of the method comparison procedure, in particular its robustness. Its application is demonstrated by several examples, and the results are compared with other robust biometrical procedures. The mathematical aspects are explained in the appendix.

A multicentre evaluation of the Boehringer Mannheim/Hitachi 704 analysis system.

The selective multitest Boehringer Mannheim/Hitachi 704 analysis system was examined according to the ECCLS guidelines in a multicentre evaluation involving four laboratories. Ten routine parameters, covering most of the application settings of the instrument, were measured in the respective laboratory at temperatures 25, 30 or 37 degrees C. The trial lasted four months and gave more than 40,000 data. It yielded the following results: 1. Within the four laboratories the mean coefficients of variation for three control sera at different concentrations were found to be equal to or better than 1.6% for the within-run imprecision and 2.8% or better for the between-day imprecision. 2. No drift was observed during eight hours. 3. Because of the high linear measuring range a re-run analysis was seldom necessary. 4. Sample-related carry-over was not seen. Reagent-dependent carry-over was measured from cholesterol to uric acid and from triacylglycerols to lipase. Through modification of the cholesterol and triacylglycerol reagents, the carry-over effect was practically eliminated. 5. The recovery of the assigned values of control sera showed average values between 99 and 104%. For bilirubin, creatinine, creatine kinase and alanine aminotransferase some control sera showed deviations greater than 10%. 6. In all cases, regression analysis of the results obtained in comparisons of the present instrument with the Hitachi 705 or 737 yielded slopes close to unity with extreme values of 0.95 and 1.06. 7. During the entire evaluation period there was no malfunction or breakdown of the instruments. The evaluators came to the conclusion that the analytical performance as well as the reliability and practicability of the Hitachi 704 can be rated as excellent.

Comparison of several regression procedures for method comparison studies and determination of sample sizes. Application of linear regression procedures for method comparison studies in Clinical Chemistry, Part II.

In part I of this series (H. Passing & W. Bablok (1983), J. Clin. Chem. Clin. Biochem. 21, 709-720) we described a new biometrical procedure for the evaluation of method comparison studies. In part II we now discuss its properties and compare them with those of other established procedures by means of a simulation study. We demonstrate that the reliability of the results not only depends on the sample size but also on the sampling distribution, the precision of the methods, and the concentration range covered by the samples. Linear regression and principal component procedures are either inadequate or not as reliable as our new procedure. The appropriate sample size is discussed and recommendations are given.

Evaluation of Diabur-Test 5000: a cooperative study carried out at 12 diabetes centers.

Diabur-Test 5000, a new test strip for urinary glucose, permits the accurate measurement of up to 5% glucose concentrations in urine. In a survey carried out at 12 diabetes centers in Europe, the new test strip was tested in laboratory trials and routine self-monitoring. There was good agreement between the test strip and the quantitative glucose determination on 4105 urine samples in the laboratory trials. A total of 185 patients used Diabur-Test 5000 for self-monitoring; nearly all reported favorably on the new test strip. Both the laboratory tests (on 1677 urine samples) and self-monitoring (on 4309 urine samples) showed Diabur-Test 5000 to be more sensitive compared with other rapid diagnostic tests. The new test strip is highly suitable for the determination of urinary glucose, particularly in routine self-monitoring.

Evaluation of the Micur microdilution systems for antibiotic susceptibility testing of gram-negative and gram-positive bacteria.

Two commercial systems for testing the antimicrobial susceptibility of bacteria were evaluated in a collaborative study at two sites using 306 freshly isolated clinical strains. Gram-negative bacteria were tested with the Micur RST 02 and gram-positive bacteria with the Micur RST 03, systems for MIC titration. For categorization of bacterial susceptibility into sensitive, intermediate or resistant, the Micur ST 02 and 03 were used for gram-negative and gram-positive bacteria respectively. The broth microdilution technique served as reference method. A total of 3672 MIC pairs were determined. MICs obtained with the Micur RST 02/03 were found to be 96.9% in agreement (+/- one log2 dilution) with the reference method results. The inter-laboratory and intra-laboratory reproducibility for the Micur RST tested with four ATCC reference strains was 97.5% and 98.5% respectively. Categorization of bacterial susceptibility with the Micur ST 02/03 agreed with 94.9% of the Micur RST results and 91.6% of the reference method results. On account of their accuracy, reproducibility and long shelf-life the Micur RST and ST systems offer a convenient method for testing antimicrobial susceptibility of bacteria in the clinical microbiology laboratory.

An optimized design for the establishment of assigned values in control sera. The establishment of assigned values in control sera, IV.

From the study described in part 1 of this series (Passing, H. et al. (1981), this j. 19, 1137-1144) it has been derived in part 3 (Passing, H. (1981), this j. 19, 1153--1166) that 6 reference laboratories are appropriate for the establishment of assigned values and their uncertainty intervals in a control serum. From the same study the two outstanding characteristics of an optimized design are found: It is sufficient that each reference laboratory performs single determinations within independent series. The number of series however has no relevant influence on accuracy and precision of the assigned values. The following design is obtained: Six reference laboratories perform single determinations in five independent series each. Additionally, the complete concept of establishment of assigned values is summarized. Up to now, the model has met the expectations in practice.

[Antithrombin III: reference values found with a chromogenic substrate (chromozym TH) (author's transl)]. / Antithrombin III: Referenzwerte mit einem chromogenen Substrat (Chromozym TH).

A new kinetic assay for antithrombin III (heparin-cofactor) in plasma was used to determine reference values. Ranges of 10--15 IU/ml at 25 degrees C and 20--29 IU/ml at 37 degrees C were found for a reference population of 219 men and 204 women 15--93 years of age. There was no evidence that these values vary with age or sex, nor was there any difference between pre- and postprandial antithrombin activities, or between smokers' and non-smokers' values. None of the illnesses present in the reference population nor any related drug therapy affected the antithrombin III level, and there was no statistically significant difference between the values for women taking oral contraceptives and those who did not. However, this latter observation does not preclude the possibility of individual variation.

[Pancreatic lipase: reference values at 25 degrees C (author's transl)]. / Pankreaslipase: Referenzwerte für 25 degrees C.

Development of a new specific test for estimation of pancreatic lipase activity (EC 3.1.1.3.) required establishment of reference values. An upper reference range of 170 to 190 U/l at 25 degrees C was determined from a group of 368 females and 435 males aged 20 to 70 years. Values below 170 U/l are very likely to be normal, values above 190 U/l are considered pathological. Values between 170 and 190 U/l require further controls. For practical reasons age and sex dependency need not be accounted for as these influences are negligible.

[Creatine kinase "NAC-activated": reference values for children (author's transl)]. / Creatinkinase "NAC-aktiviert": Referenzwerte bei Kindern.

Reference values for 327 children aged between 1 day and 15 years are given for the revised standard method for the determination of serum creatine kinase (CK) activity by activation with N-acetylcysteine (NAC). No sex-dependence could be observed, but CK activity was found to vary markedly with age. The following values are suggested as upper limits of the reference ranges for measurements at 25 degrees C: neonates: 1-3 days: less than or equal to 370 U/l, 4-10 days: less than or equal to 200 U/l, 11-31 days: less than or equal to 100 U/l; children (2 months-15 years): less than or equal to 90 U/l.

[Determination of urea in blood and serum by the reflotest-urea method (author's transl)]. / Harnstoffbestimmung mit Reflotest-Urea in Blut und Serum.

Tests in five laboratories on pooled sera in three concentration ranges demonstrated good reproducibility of urea concentration with the Reflotest-Urea, at a variation coefficient from 2.4% to 5.0%. Comparison with the urease/GLDH, Berthelot and diacetylmonoxim tests on sera from routine samples indicated good agreement of results even for pathological samples. Using whole blood there was also good agreement with results with plasma of the same samples. The Reflotest-Urea method is simple because different dose ranges can be used and the reaction time of ten minutes is not crucial. In-vitro studies using 37 of the most commonly used drugs in different areas of medicine failed to reveal any interference with the test.

[A specific fully enzymatic method for creatinine: reference values in serum (author's transl)]. / Referenzwerte für Kreatinin im Serum, ermittelt mit einer spezifischen enzymatischen Methode.

Reference values for creatinine in serum were established using a fully enzymatic method, adapted to a discontinuous analyzer. Our reference group included 250 females and 215 males (blood donors, hospital staff and patients) aged 18-70 years. Up to 60 years, creatinine concentration did not depend on age, but there was a significant difference between the creatinine concentrations of women and men. We propose reference ranges for creatinine in serum (95% range) of 44-80 mu mol/l for women and of 44-97 mu mol/l for men.