ECAT FOUNDATION. External quality Control of diagnostic Assays and Tests with a focus on Thrombosis and Haemostasis

Transcription

1 ECAT FOUNDATION External quality Control of diagnostic Assays and Tests with a focus on Thrombosis and Haemostasis SURVEY MANUAL 2016

2 ECAT FOUNDATION Postal address Visiting address ECAT Foundation ECAT Foundation P.O. BOX 107 Dobbeweg AC Voorschoten 2254 AG Voorschoten The Netherlands The Netherlands Contact details (general) Contact details (financial department) T T F F E. info@ecat.nl E. finance@ecat.nl W. Registration no. at the Chamber of Commerce: VAT number: NL B01 IBAN no.: NL38 INGB BIC code: INGBNL2A

3 I N T R O D U C T I O N Dear sir, dear madam, It is our pleasure to present to you our Survey Manual This Survey Manual provides you with detailed information and instructions about the surveys of the ECAT external quality assessment programme It includes for instance the survey schedule, information about the surveys, statistics and reports as well as instructions about testing, reporting results and the download of survey reports. For general information about the ECAT organisation, accreditation, distributors, invoices, cancellation, extra orders etc., we refer to the brochure Participant Information distributed during mailing about the annual subscription This brochure can also be downloaded from the participant area at the ECAT website ( For those that participate in the POCT INR programme, instructions will be provided with the first distribution of QC sets in Participants will receive an annual certificate of participation at the end of the year. Please keep this Survey Manual carefully during the entire year COMPLAINTS AND APPEALS Any complaint regarding the delivery of samples, result submission and reports should be directed in written to the ECAT office (for contact details: see ECAT office information at the inner cover page) Any complaint regarding a survey report should be sent to the ECAT within 6 weeks after the issue date of the online report. The final date for submitting complaints is indicated in the survey report. Complaints received after this date are no longer considered. Any appeal regarding the activities of the ECAT Foundation should be directed in written to the Supervisory Board of ECAT. Contact details of the board: ECAT Foundation attn. Secretary Supervisory Board P.O. Box AC Voorschoten The Netherlands Dr. Piet Meijer Director Mrs. Aletta Veninga Scheme Manager ECAT Foundation Page 1

4 C O N T E N T CONTENT SURVEY SCHEDULE... 3 PROGRAMME DETAILS... 4 Main programme... 4 Screen programme... 4 Molecular Biology... 5 Special surveys... 5 Disclaimer:... 5 DISTRIBUTION OF SAMPLES... 6 General information... 6 Receipt of samples... 6 Survey Instructions... 6 INSTRUCTIONS FOR TESTING... 7 General information... 7 Instructions for reconstitution... 7 Use of Latex Immuno Assays... 7 Instructions for Lupus Anticoagulant testing... 7 RESULT SUBMISSION... 8 General information... 8 General instructions for results submission via internet... 9 Specific instructions for the Screen and D-Dimer module Instructions for D-Dimer Specific instructions for the Lupus Anticoagulant module Special instructions for the von Willebrand Factor module Submission results molecular biology surveys Submission electronic post-analytical platelet function survey STATISTICAL EVALUATION Statistical evaluation of survey results Explanation of Algorithm A DOWNLOAD SURVEY REPORTS Instructions to download survey reports SURVEY REPORTS General remark General explanation of the survey report ECAT PARTICIPANTS MEETING ECAT Foundation Page 2

5 S U R V E Y S C H E D U L E SURVEY SCHEDULE Screen Module (sample dispatch early February 2016) Survey Survey period Closing Date 2016 S February 20 February 2016 S April 16 April 2016 S June 18 June 2016 S August 20 August 2016 S October 22 October 2016 S6 5-9 December 10 December Plasma Tests Main Programme Survey Dispatch Date Closing Date Closing Date D-Dimer March 2 April 16 March May 25 June 8 June August 24 September 7 September November 10 December 23 November Molecular Biology, DNA Sequencing and DNA Isolation (via DGKL, Germany) Survey Type Dispatch Date Closing Date MG1 1/16 Molecular Biology MG1 A-F 16 March 9 April MG1 2/16 Molecular Biology MG1 A-F 21 September 15 October MG2 1/16 Molecular Biology MG2 A-F 16 March 9 April MG2 2/16 Molecular Biology MG2 A-F 21 September 15 October SQ1/16 DNA Sequencing 10 February 5 March SQ2/16 DNA Sequencing 31 August 24 September DI1/16 DNA Isolation 9 March 2 April DI2/16 DNA Isolation 31 August 24 September Other surveys Type Post Analytical Platelet Function EQA (via Nascola, USA) Platelet Dense Granule exercise (via Nascola, USA) Case studies on bleeding disorders Pre- and post-analytical electronic survey Period June, December (2 surveys per year) Spring, Autumn (2 surveys per year) Spring, Autumn (2 Survey per year) Autumn (1 survey per year) ECAT Foundation Page 3

6 P R O G R A M M E D E T A I L S PROGRAMME DETAILS Main programme The table below shows which modules are distributed in a particular survey. Module Thrombophilia module: * A. Antithrombin (activity and antigen), Protein C (activity [chromogenic and clotting] and antigen), Protein S activity, Protein S antigen (total and free). B. APC Resistance Lupus Anticoagulant / Antiphospholipid Antibodies No. of surveys / year 4 4 No. of different samples / survey 2 2 No. of vials / sample code 2 1 Survey composition D-Dimer Coagulation Factor module I (Factor VIII, IX, XI and XII) Coagulation Factor module II (Factor II, V, VII and X) Von Willebrand Factor module (antigen, activity, collagen binding, multimers, Factor VIII) ADAMTS-13 (activity and antigen) ADAMTS-13 (inhibitor) Factor XIII Fibrinolysis parameters I (Plasminogen, Antiplasmin) Fibrinolysis parameters II (t-pa, PAI-1) Unfractionated Heparin Monitoring (anti-xa) Low-Molecular Weight Heparin Monitoring (anti-xa) Homocysteine Factor VIII inhibitor Factor IX inhibitor Thrombin Generation Test HIT Immunological assays HIT Functional assays Orgaran (quantitative) Fondaparinux (quantitative) Rivaroxaban (quantitative) Apixaban (quantitative) Argatroban (quantitative) Dabigatran (quantitative) ROTEM / TEG Screen programme The screen module includes 6 surveys per year. All annual samples for the screen module are distributed at once and separately from the samples of all other modules. Module Screen module: APTT, PT, INR, Fibrinogen No. of surveys / year No. of Different samples / survey No. of vials / sample code S1 Survey composition S S S S S6 ECAT Foundation Page 4

7 P R O G R A M M E D E T A I L S Molecular Biology In co-operation with the DGKL in Germany several EQA programmes related to Molecular Biology are provided. Molecular Diagnostic Testing Twice a year an EQA programme for Molecular Diagnostic Testing is provided. There are two modules on molecular genetic testing (MG1 and MG2), each including 6 sets with different genetic defects to be tested. For details see table below. The material provided is purified DNA. MG1 Molecular Genetics MG1 Set A: FV-Leiden, Prothrombin, MTHFR (C677T, A1298C), PAI-I 4G5G MG1 Set B: FXIII V34L, GPIIIa, βfib (g455a), VKORC1 (G-1639A/C1173T), FXII c46t, FV-H1299R MG1 Set C: a1 PI, Apo E, ApoB100, ACE, CETP MG1 Set D: Aldo B (149,174,334), HFE (H63D, C282Y, S65C), LCT c-13910t, NOD2 (R702W, G908R, L1007fins C) MG1 Set E: M. Wilson (ATP7B-C3207A), FSAP (Marburg-I), ITGA2 Gplalla C807T, Col1A1 SP1, VDR (BsmI/Apal,TaqI) MG1 Set F: Faktor VII (R353Q), AT3 Cambridge Typ I/II, CYP3A5*3 MG2 Molecular Genetics MG2 Set A: TPMT, CYP2C8 (K399R), CYP2C9 *2/*3, UGT1A1 (*28), DPD Ex 14 skipping, BCHE A/K MG2 Set B: K-Ras: Codon 12/13/61, BRAF V600E MG2 Set C: HLA-B27, TNF alpha (238, 308) MG2 Set D: CYP2D6, CYP2C19 (*2/*17) MG2 Set E: HLA B*5701, CYP2B6*6 MG2 Set F: IL28B (C/T Polymorphismus), IL6 (G174C), CYP3A4*22 DNA isolation Twice a year an EQA programme for DNA isolation is provided. Here whole EDTA-blood is provided. These surveys focus on the determination of concentration of DNA, ratio 260/280, method of identification and defined genotypes. The genotypes included in these surveys are FV-Leiden (ARG206GLN), FV-H1299R (HIS1299ARG), FV-Cambridge (ARG306THR), FV-Hong-Kong (ARG306GLY), FII-g20210a, MTHFR C677T, HFE (H63D, C282Y, S65C). DNA sequencing Twice a year an EQA programme for DNA sequencing is provided. Purified DNA is provided. DNA sequencing should be performed and corresponding diagnostic interpretation should be given. Special surveys Electronic post-analytical platelet function survey: In co-operation with the NASCOLA in the United States twice a year a post-analytical survey for platelet function testing is provided. These surveys focus on the interpretation of aggregation patterns in combination with a case description. Platelet Dense-Granual Survey: In co-operation with the NASCOLA in the United States once per year a platelet dense-granule survey is provided. This is a paper or electronic challenge in which electron microscopy images have to be evaluated. Case studies on bleeding disorders: Case studies on bleeding disorders is a combination of analytical aspects as well as case-based interpretation of the laboratory results. The participant will receive plasma to perform laboratory tests, which can be selected based on a given case description. Genetic testing will be included as an option. In addition a questionnaire on the interpretation of test results has to been completed as well. The scope of this case studies is to investigate the ability of proper interpretation of the clinical case description and the obtained laboratory test results resulting in the correct diagnosis. Pre- and post-analytical survey: This is an electronic survey in which multiple choice questions with respect to aspects of the pre- and postanalytical phase have to be answered. Comments on the given answers are shown and an overview of the score is given. Disclaimer: The ECAT Foundation is not responsible for either the content or the evaluation of the test results of surveys provided either by the NASCOLA or DGKL. ECAT Foundation Page 5

8 D I S T R I B U T I O N O F S A M P L E S DISTRIBUTION OF SAMPLES General information Samples are sent to participants according to the survey schedule and survey composition. Samples used in the surveys are human-based plasmas. To maintain stability and for practical purposes during the distribution process, the samples are lyophilized. The plasma samples have been tested by an FDA approved method for the presence of HIV antigen, hepatitis B surface antigen as well as for hepatitis C antigen and have been found to be negative. As with all preparations of human origin, suitable precautions should be taken in the handling and disposal. The samples are packed in plastic bubble bags and carton boxes to prevent damage during transport. Each vial has a label with the ECAT logo, survey number, sample code, volume for reconstitution and module name. This code corresponds with a code in the sample list on the survey instruction. This sample code is also the identification code when results are reported. Example label: ECAT Sample : Volume : 0.75 ml Survey : Module : Thrombophilia Receipt of samples Samples should be received within one week after the dispatch date (see survey schedule page 3). If samples are not received after one week, the ECAT office should immediately be informed, preferably by (info@ecat.nl). ECAT cannot guarantee timely receipt of samples within the survey period if the ECAT is not informed of missing samples after one week of the dispatch date. After receipt the samples should be stored at 2-8 C until use. Survey Instructions Together with the samples detailed Survey Instructions are provided. These instructions include: information about the samples of each module the volume of reconstitution safety matters Participants can also download the Survey Instructions from the participants area at the website. Example survey instructions: ECAT Foundation Page 6

9 I N S T R U C T I O N S F O R T E S T I N G INSTRUCTIONS FOR TESTING General information The ECAT plasmas should be treated as regular patient plasmas and included in the normal daily analytical process in the laboratory. The regularly used methods should be applied. No special treatment of the samples is allowed. Results should be reported similar as a result of a patient is reported. Instructions for reconstitution For proper reconstitution of the plasmas, please follow exactly the instructions below: The vial must reach room temperature before adding distilled water. Dissolve the content of each vial in sterile, distilled, room temperature water. For the exact volume of water to be used: see survey instruction leaflet. Leave the vial for 5 minutes. Swirl the vial gently to mix and leave for a further 15 minutes for complete reconstitution. Before use mix the vial again gently. Reconstituted plasma should preferably be used within 1 hour after reconstitution. Plasma should be stored at room temperature after reconstitution. For immunological methods the reconstituted plasma can be stored for 1 month at -20 C. Use of Latex Immuno Assays For the application of ECAT plasmas into Latex-Immuno-Assays test we advise you to centrifuge the reconstituted plasma for at least 10 minutes at x g. Instructions for Lupus Anticoagulant testing According to the guidelines of the Standardization and Subcommittee (SSC) of the International Society of Thrombosis and Haemostasis (ISTH) for Lupus Anticoagulant (LA) a laboratory should perform: At least 2 different screening tests based on different methodology (e.g. APTT and DRVVT). A mixing study should be performed to exclude whether a prolonged clotting time was related to a factor deficiency. It should be confirmed that the prolonged clotting time is phospholipid-dependent. Therefore each test panel exists of three different tests, a screening test, a mixing study and a confirmation test. The ECAT External Quality Assessment Programme provides the ability to report the results for three different test panels. These different test panels are not meant to report repeated measurements with the same reagent. Additional information for users of the STAGO Staclot LA method: This test is an APTT-based confirmation test and should be reported as such. The result obtained with this test is reported as a difference in measured clotting times. It should be reported with the unit Delta seconds. Normal plasma In the evaluation of the reported test results the ratio between the ECAT plasma and the laboratories own normal plasma is calculated. To make the calculation of this ratio possible the measured clotting time for the normal plasma should be reported. The report box for normal plasma is not meant to report a reference range for normal plasma. Ratio screen/confirm The ratio screen / confirm is frequently used as an evaluation tool to assess the LA positivity of a sample. Here the ratio of the result of the screening test and the confirmation test should be reported. No other ratios should be reported in this result box. ECAT Foundation Page 7

10 R E S U L T S U B M I S S I O N RESULT SUBMISSION General information Results can only be submitted via the results submission facility in the participants area of our website. If you do not have a password to login for this facility, please contact the ECAT office. For instructions about the use of the result submission facility see page 9. Inappropriate completion of the report forms may lead to exclusion of the results from the statistical evaluation. Results returned after the closing date of the survey (see survey schedule) will not be included in the evaluation. To standardise the display of results these should be reported for each parameter with the below indicated number of decimals. Parameter No of decimals Parameter No of decimals APTT / PT 1 PAI-1 antigen 1 INR 2 PAI-1 activity 1 Fibrinogen 0 t-pa antigen 1 Antithrombin activity 0 Anti-Xa (UFH / LMWH) 2 Antithrombin antigen (%) 0 Anti-Xa (Orgaran / Fondaparinux / Rivaroxaban, Apixaban) Antithrombin antigen (mg/dl) 1 Argatroban (anti-iia / dtt) 2 Protein C (activity and antigen), 0 Dabigatran (anti-iia / dtt) 0 Protein S (activity and antigen) 0 Homocysteine 1 APC Resistance (ratio) 2 Factor VIII inhibitor (titer) 1 Lupus anticoagulant (clotting times) 1 Factor IX inhibitor (titer) 1 Lupus anticoagulant (ratio) 2 Thrombin Generation lag time (min) 1 D-Dimer (ng/ml) 0 Thrombin Generation time to peak (min) 1 D-Dimer (mg/l) 2 Thrombin Generation peak thrombin (nm) 0 Coagulation Factor activity (Factor II, V, VII, VIII, IX, X, XI and XII) Von Willebrand Factor module (antigen, activity, collagen binding, FVIII) 0 Thrombin Generation Velocity Index 1 0 Thrombin Generation ETP/AUC 0 ADAMTS13 (activity / antigen) 0 HIT (OD) 3 ADAMTS13 (inhibitor) 1 HIT (U/mL) 1 Factor XIII activity 0 HIT (%) 0 Factor XIII antigen (%) 0 ROTEM (CT) 0 Factor XIII antigen (mg/dl) 1 ROTEM (MCF) 0 Plasminogen activity 0 TEG (R) 0 Plasmin Inhibitor 0 TEG (MA) 0 2 ECAT Foundation Page 8

11 R E S U L T S U B M I S S I O N General instructions for results submission via internet FOR ANY PROBLEM WITH RESULT SUBMISSION PLEASE CONTACT THE ECAT OFFICE: INFO@ECAT.NL IMPORTANT INFORMATION For decimals only use. (dots) and no comma s. Do not add text to the result fields. 1. Homepage Start ECAT website: Select at ECAT homepage the option: Login 2. Login Before you can enter the participant area you have to login. Enter your Username (=Labcode) and your Password (provided by ECAT) Select: Log me in 3. Participant Area You are now in the Participant Area of the ECAT website. Select in the menu: Result submission ECAT Foundation Page 9

12 R E S U L T S U B M I S S I O N 4. Result submission You are now at the page where you can go to the Result Submission facility. Select in Submit Results (You are now directed to the result submission facility. In some cases it may happen that there is a communication failure with the data base for result submission. In such an occasion an extra login is necessary. This will be indicated at the screen) At this page also important instructions can be given from the ECAT office and/or webmaster regarding results submission issues. 5. Selection of module On your screen you will see an overview of all modules you have subscribed for. Select the module for which you will enter results, e.g. Thrombophilia (click on Thrombophilia ). 6. Selection of Analyte On your screen you will see an overview of all the tests belonging to the selected module. Select under Assay the analyte for which you will enter results (click on the name of the analyte), e.g. Antithrombin (click on Antithrombin ). When a resubmission is necessary in the case of an observed error, please select again the analyte in the Assay list. The last submitted result will be used for statistical analysis. 7. Enter results Enter results: Complete the fields for assay, method, equipment, result, unit and interpretation (use blue arrows to select options). All the mentioned fields are required! Results can not be submitted if one of the fields is not completed. If you have any comments to add, the text box for notes can be used. Do not add comments to the result fields. For decimals use only. (dots) and no comma s. If no exact quantitative test results can be given (e.g. the test results is above the upper limit of the calibration curve e.g. > 120% -) enter in the number in the result field and select in the field < or > the appropriate indicator. Select: Print (print form for your own files). Select: Submit (to send results to the ECAT database). ECAT Foundation Page 10

13 R E S U L T S U B M I S S I O N 8. Submission confirmation After correct completion of the result sheet and submission of the results a confirmation of a successful result submission will be given. Here the option can be selected to return to the list of assays of the module selected before or return to the list of modules belonging to your subscription profile. 9. View function The view function is only meant to review your last submitted results. When you have submitted results the date of submission, the sample codes and your participant number will appear in the header. So here you can check your latest submission yourself. Specific instructions for the Screen and D-Dimer module Starting in 2016 it will be possible to submit for both the Screen and D-Dimer module results for a maximum of three different instrument and/or reagents within one result form (no different login codes necessary anymore). The results of the different instruments/reagents will be included in the same survey report. Instructions for D-Dimer Selection of units: Please select the appropriate units. Use only the original units of the method (i.e. D-Dimer units or FEU). Also select within the unit-group the correct measuring unit: ng/ml or mg/l. When incorrect units are selected the results will not be included in the survey evaluation! Tinaquant method: Citrate plasma If the method is calibrated for the use of citrated plasma select in the method list the Tinaquant (citrate plasma). Heparin plasma Because ECAT always provides citrated plasma in their surveys you have to correct your results before submission in the case you use heparin plasma. Please multiply the measured result with the correction factor If the method is calibrated for the use of heparin plasma select in the method list the Tinaquant (heparin plasma). ECAT Foundation Page 11

14 R E S U L T S U B M I S S I O N Specific instructions for the Lupus Anticoagulant module The Lupus Anticoagulant Module consist of several panels. First a selection should be made for which parts of a panel test results will be submitted. Activate the panel by selecting the panel button. After data entry of the first panel you can return to the main screen of the Lupus Anticoagulant module where you can continue with the next panel. See instructions below. Data entry Lupus Anticoagulant module: 1. Select the appropriate parts of panel 1: In this example the screening and confirmation tests are selected. Select: Panel 1 2. Complete the results sheet for panel 1. (Same procedure as described in the general instructions) Use for decimals only. (dots) and no comma s. Do not add comments to the result fields. Select: Print (print form for your own files). Select: Submit (to send results to the ECAT database). 3. If you would like to submit results for more Lupus Anticoagulant panels or for Phospholipid Antibodies, please select Assays. You will return to the main Lupus Anticoagulant screen where you can select the next panel. Repeat step 1 3 when appropriate. 4. After submission of all your results, please select Final conclusion. ECAT Foundation Page 12

15 R E S U L T S U B M I S S I O N 5. Select the appropriate conclusion and submit. After submission you can return to the list of modules. ECAT Foundation Page 13

16 R E S U L T S U B M I S S I O N Specific instructions for the von Willebrand Factor module The Von Willebrand Factor Module consist of several test. Here first a selection should be made for which analytes test results will be submitted. After activation of the selection only the selected test will be shown for data entry. See instructions below. Data entry VWF module: 1. Select the appropriate tests: In this example VWF antigen and ristocetin cofactor activity are selected. Select: Activate Selection 2. Complete the result sheet as described above. (Same procedure as described in the general instructions) Use for decimals only. (dots) and no comma s. Do not add comments to the result fields. Select: Print (print form for your own files). Select: Submit (to send results to the ECAT database). 3. Before you return to the list of modules do not forget to select and submit your VWF interpretation. ECAT Foundation Page 14

17 R E S U L T S U B M I S S I O N Submission results molecular biology surveys These surveys are provided by the DGKL-RfB in Bonn Germany. Results for these modules should be directly submitted to the DGKL-RfB. Codes for modules: MG = Molecular Genetics DI = DNA isolation SQ = DNA sequencing There are two possibilities for result submission. 1) Via the report forms included with the samples and follow the instructions given by DGKL-RfB. 2) Via the website of DGKL-RfB ( Homepage DGKL-RfB: At the right top corner of the homepage you can login. A specific participant number and password are needed. Do not use your ECAT login details here! To obtain this specific participant number and password please select the option: Don t have an account yet. Please register. Follow the instructions given on the registration page (see below). The DGKL-RfB will provide you with the participant number and password by . Important note! In the particicpants area of the DGKL-RfB website you can also order surveys. Don t use this option. Only register via the ECAT office. This to avoid double registrations. Result submission: First log in at the homepage of the DGKL-RfB website. Make the appropriate selection for submission of your results. Submission electronic post-analytical platelet function survey Participants for the post-analytical platelet function survey will receive via NASCOLA by with each survey the Platelet Aggregation EQA system User Guide, including specific instructions for the submission of results. ECAT Foundation Page 15

18 S T A T I S T I C A L E V A L U A T I O N STATISTICAL EVALUATION Statistical evaluation of survey results For the external quality assessment programme of the ECAT the robust average of the results reported by all participants in the survey is used as the assigned value (= consensus value). In accordance with ISO/IEC standard 17043:2010 and ISO standard 13528:2005 Algorithm A is used as a robust statistical for the calculation of the consensus value and the standard deviation. Further explanation on Algorithm A can be found at page 17. The standard procedure for the evaluation of quantitative test results is as follows: Results are harmonised to the same unit (% / U/dL). The consensus value and standard deviation (SD) using Algorithm A. Based on this consensus value and SD the between-laboratory variation is calculated. Algorithm A is applied on the total group and the level of and method if there are at least 10 participants included in the same group (for the screen assays and homocysteine the minimum number is 5). The consensus values are represented in the report as assigned value (see explanation of the report in paragraph 16.1). For groups with less than 10 participants (for the screen assays and homocysteine less than 5 participants) the median is used as target value. The measurement uncertainty of the consensus values is displayed by: U = uncertainty AV = assigned value s = standard deviation p = number of participants U AV = 1.25 x s / p This information can be obtained from the report as follows: cv and p can be obtained from the report. s can be calculated from the coefficient of variation (CV) and the consensus value by the following formula: Performance Indicator s = (CV/100) x AV As an individual performance indicator the Z-score is calculated. Z-score The z-score is calculated as follows: [(laboratory result) - (mean result of all laboratories)] / (standard deviation of all results) The Z-score is al so calculated for groups on the level of and method with at least 10 participants. Acceptance criteria Each participants should carefully evaluate the Z-scores given in the report. In accordance with ISO/IEC standard 17043:2010 and ISO standard 13528:2005 the following acceptance criteria are used: -2 < Z-score < 2 : The result is acceptable -3 < Z-score < -2 or 2 < Z-score < 3 : The results is questionable (warning signal) Z-score < -3 or Z-score > 3 : The result is unacceptable (action signal) A single action signal or two warning signals in consecutive exercises shall be taken as evidence that a anomaly has occurred that requires investigation by the laboratory. ECAT Foundation Page 16

19 S T A T I S T I C A L E V A L U A T I O N Explanation of Algorithm A Algorithm A is mainly based on the robust statistical model of Hampel. From the original data set the initial mean value (x*) and standard deviation (s*) are calculated. As initial value for x* the median is taken and as initial value for s* the median absolute deviation (MAD) is calculated. The MAD is defined as s* = x median x i x*. In other words, for each value of the data set the absolute deviation of the initial mean value (x*) is calculated. From this set of deviations the median is taken and multiplied by This value is defined as the initial standard deviation. Then limits for the distribution of the data set are calculated. These limits are defined as x* ± δ, where δ = 1.5 x s*. If any value of the data set is outside these limits this value is transformed to the value of the limit. From this new data set a new x* and s* are calculated, where s* is defined as s* = x (x i - x*) 2 /(p 1). [x i = values from the transformed data set, p = number of results]. With this new x* and s* new limits (δ) are calculated. These news limits are applied to the original data set, results outside the limits are transformed to the limit values and new x* and s* are calculated. This procedure is repeated until the process converges. Convergence may be assumed when there is no change from any one iteration to the next in the third significant figure of the standard deviation or of the equivalent figure of the mean value. The final mean value obtained and the standard deviation are used for the calculation of the betweenlaboratory coefficient of variation and the Z-score. The Z-score of an individual result is calculated on the basis of the value in the original data set. An example of the application of Algorithm A is given in figure 1. Fig. 1 Example of application of Algorithm A to a data set with 4 iteration steps. [Example taken from a presentation by Dr Koch, University of Stuttgart, Germany, given at the PT Conference in Sibiu, Romania Background Literature Daszykowski M. et al (2007). Robust statistics in data analysis. Chemometrics and Intel Lab Systems 85: Hampel F. (1974). The influence curve and its role in robust estimation. J. Am. Statist. Assoc. 69: Huber P.J. (1964). Robust estimation of a location parameter. Ann. Math. Statist. 35: Huber P.J. (1965). A robust version of the probability ratio test. Ann. Math. Statist. 36: ISO 13528:2005. Statistical methods for use in proficiency testing by interlaboratory comparisons. ISO 17043:2010. Conformity assessment General requirements for proficiency testing. ECAT Foundation Page 17

20 D O W N L O A D S U R V E Y R E P O R T S DOWNLOAD SURVEY REPORTS Instructions to download survey reports Within the external quality assessment programme of the ECAT Foundation the following survey reports are distinguished: Type of survey report Screen Main Lupus Anticoagulant D-Dimer HIT Immunological HIT Functional TGT ROTEM / TEG Modules/Parameters APTT, PT/INR, Fibrinogen Thrombophilia, Coagulation Factor module I and II, Von Willebrand Factor module, ADAMTS13, Factor VIII inhibitor, Factor IX inhibitor, Factor XIII, Fibrinolysis module I and II, Unfractionated Heparin, Low-Molecular Weight Heparin, Homocysteine Orgaran, Fondaparinux, Rivaroxaban, Apixaban, Argatroban, Dabigatran Lupus Anticoagulant / Antiphospholipid Antibodies D-Dimer HIT immunological assays HIT functional assays Thrombin Generation Test ROTEM (CT, MCF) / TEG (R, MA) Note: The availability of a particular report and/or modules within the main report depends on the survey composition (see schedule page 4) 1. Homepage Start ECAT website: Select at ECAT homepage the option: Login 2. Login Before you can enter the participant area you have to login. Enter your Username (=Labcode) and your Password (provided by ECAT) Select: Log me in ECAT Foundation Page 18

21 D O W N L O A D S U R V E Y R E P O R T S 3. Participant Area You are now in the Participant Area of the ECAT website. Select in the menu: Survey Reports 4. Download Survey Reports You are now at the page where you can go to the area where you can download survey reports. Select in Download Reports 5. Select and download Survey Report You are now at the page where you can download survey reports. Select from the appropriate survey the report you would like to download. The last survey is always on the top of the list. Reports up to two years ago can be downloaded. In this example the D-Dimer report is selected. You can now print and/or save the report to your own computer. Note: Survey reports are available in PDF-format. To be able to read the reports it is important that Acrobat Reader is installed on your computer. ECAT Foundation Page 19

22 S U R V E Y R E P O R T S SURVEY REPORTS General remark When results are not correct presented in the survey report caused by a mistake of the participant (e.g. a wrong result was submitted) no new survey report will be provided. When results are not correct presented in the survey report caused by a fault of ECAT a new report will be provided. From each survey an individual survey report will be provided. Each report includes a front page, general page and the evaluation of the survey results for those modules a participant has subscribed for. Below a description of the report is given. General explanation of the survey report Front page The front page exposes the type of report, survey number and labcode. General page This page includes the report issue date, the survey number and the type of report as well as general information. Here is also stated that the Survey Manual 2016 should be considered an integral part of the survey report. Survey report pages For each analyte a participant has subscribed for in the ECAT programme a report is given. The report consists of the following parts: 1. The header 2. The graph 3. The table 4. Z-score plot 5. Z score history plot The header The header of each report sheet consist of two parts. At the top of each page the survey number, number of pages of the report, the date the report is issued and the labcode is indicated. Also the name of the module and the analyte is indicated. In addition, information about the number of responders, the sample used, the units in which the results are reported, the stability and homogeneity of the sample are given. Example of general information ECAT Foundation Page 20

23 S U R V E Y R E P O R T S When appropriate the clinical classification is given in a separate table. Example of classification table The graph The distribution of the results is represented in a histogram. Depending of the analyte the results are grouped based on the assay principle or the method used. The position of your own result within the distribution is indicated by a black arrow on top of the bar in question in the histogram. The table The table given in the report show the descriptive statistics for all results and for each assay principle and method. The target value represent the consensus value as calculated by Algorithm A. The between-laboratory variation (CV) and Z-score are only given when at least 10 participants belong to the same group (for the homocysteine this number is 5). The group(s) to which your results belongs are highlighted in grey. Z-score plot The relationship of the Z-scores of the two different samples are plotted in a Z- score plot. The Z-score plot only includes methods with at least 10 participants. The relationship of both Z-scores gives an indication if the deviation from the mean value of your particular method is caused by systematic and/or random errors. ECAT Foundation Page 21

24 S U R V E Y R E P O R T S The table below shows for each of the parameters which Z-scores are used for the Z-score plot. Description Screen assays Thrombophilia module Antithrombin, Protein C, Protein S APC Resistance Lupus Anticoagulant / Antiphospholipid Antibodies D-Dimer Coagulation Factor module I (Factor VIII, IX, XI and XII) Coagulation Factor module II (Factor II, V, VII and X) Von Willebrand Factor module (antigen, activity, collagen binding, multimers, Factor VIII) Factor XIII Fibrinolysis parameters I (Plasminogen, Antiplasmin) ADAMTS-13 (activity and antigen) ADAMTS-13 (inhibitor) Fibrinolysis parameters II (t-pa, PAI-1) Unfractionated Heparin Monitoring (anti-xa) Low-Molecular Weight Heparin Monitoring (anti-xa) Homocysteine Factor VIII inhibitor Factor IX inhibitor Thrombin Generation Test HIT Immunological assays HIT functional assays Orgaran (quantitative) Fondaparinux (quantitative) Rivaroxaban (quantitative) Apixaban (quantitative) Argatroban (quantitative) Dabigatran (quantitative) ROTEM/TEG Category of Z-score reagent method method not applicable not applicable not applicable not applicable Z-score history plot The history of the Z-score for a period of one year is given in a Z-score history plot. The dashed lines in the Z-score history plot indicates the level of -1/1, -2/2 and -3/3. ECAT Foundation Page 22

25 S U R V E Y R E P O R T S ECAT PARTICIPANTS MEETING In 2016 the ECAT Foundation will organise their biennial symposium. Please reserve already the dates. More detailed information will follow in Spring th ECAT Participants Meeting Leiden The Netherlands 10 and 11 November 2016 ECAT Foundation Page 23