Clinica Chimica Acta 446 (2015) 61–63
Contents lists available at ScienceDirect
Clinica Chimica Acta journal homepage: www.elsevier.com/locate/clinchim
Case report
The External Quality Assessment Scheme (EQAS): Experiences of a medium sized accredited laboratory Vivek Bhat ⁎,1, Preeti Chavan 1, Chital Naresh 1, Pratik Poladia 1 Advanced Center for Treatment Research and Education in Cancer, Tata Hospital, Kharghar, Navi Mumbai, India
a r t i c l e
i n f o
Article history: Received 14 January 2015 Received in revised form 3 April 2015 Accepted 6 April 2015 Available online 14 April 2015 Keywords: Quality Assessment Laboratory
a b s t r a c t Introduction: We put forth our experiences of EQAS, analyzed the result discrepancies, reviewed the corrective actions and also put forth strategies for risk identification and prevention of potential errors in a medical laboratory. Methods: For hematology, EQAS samples – blood, peripheral and reticulocyte smears – were received quarterly every year. All the blood samples were processed on HMX hematology analyzer by Beckman-Coulter. For clinical chemistry, lyophilized samples were received and were processed on Siemens Dimension Xpand and RXL analyzers. For microbiology, EQAS samples were received quarterly every year as lyophilized strains along with smears and serological samples. Results: In hematology no outliers were noted for reticulocyte and peripheral smear examination. Only one outlier was noted for CBC. In clinical chemistry outliers (SDI ≥ 2) were noted in 7 samples (23 parameters) out of total 36 samples (756 parameters) processed. Thirteen of these parameters were analyzed as random errors, 3 as transcriptional errors and seven instances of systemic error were noted. In microbiology, one discrepancy was noted in isolate identification and in the grading of smears for AFB by Ziehl Neelsen stain. Conclusion: EQAS along with IQC is a very important tool for maintaining optimal quality of services. © 2015 Elsevier B.V. All rights reserved.
1. Introduction For any clinical laboratory wishing to improve its quality standards and provide the best possible results, participation in an External Quality Assessment Scheme (EQAS) is an important activity towards achieving the same [1]. EQAS helps the laboratories assess their accuracy as well as bias of their results and stability of methods over a longer period of time [2]. It serves as an educational tool by identifying staff training needs and helps to monitor and improve the performance of the laboratory by providing early warning for systematic problems associated with the respective methods. It also provides assurance to consumers (physician and patients), that the laboratory results are reliable by establishing objective evidence of testing quality [3]. Participation in EQAS is mandatory for accreditation and they complement each other dynamically to ensure high quality standards. Eventually, a satisfactory EQAS result will ensure that all the requirements of the accreditation standards are met. At our center, the diagnostic laboratories are accredited by the National Accreditation Board for Testing and Calibration Laboratories (NABL). The hematology, clinical chemistry, and microbiology ⁎ Corresponding author at: Department of Microbiology, Advanced Centre for Training, Research and Education in Cancer (ACTREC), Kharghar, Navi Mumbai- 410210, India. E-mail address: [email protected] (V. Bhat). 1 Tel.: +91 2227405093, +91 9867793325 (mobile).
http://dx.doi.org/10.1016/j.cca.2015.04.007 0009-8981/© 2015 Elsevier B.V. All rights reserved.
laboratories participate in their respective EQAS programs. The hematology laboratory participates in an EQAS program (ISHTMAIIMS EQAP) conducted by All India Institute of Medical Sciences (AIIMS), New Delhi, India. The Clinical chemistry laboratory participates in monthly clinical chemistry program conducted by BIO-RAD (Accredited to ISO/IEC 17043:2010) in which more than two hundred and fifty laboratories participate. The peer groups are divided depending on the equipment and method of tests employed for the particular parameter. The microbiology laboratory participates in the EQAS provided by Indian Association of Medical Microbiologists (IAMM). In this study, we have attempted to put forth our experiences of EQAS, analyzed the result discrepancies, reviewed the corrective actions and also put forth strategies for risk identification and prevention of potential errors in a medical laboratory. 2. Materials and methods For hematology, EQAS samples – blood, peripheral and reticulocyte smears – were received quarterly for the review period of 2011–2013. All the blood samples were processed on HMX hematology analyzer by Beckman-Coulter in duplicate as recommended by the provider and values reported for WBC, RBC, hemoglobin, MCV, MCH, MCHC and platelet counts. Peripheral smears were received with a brief relevant history about the case and significant laboratory findings like Hb, WBC, and platelet count. Participants had to submit their results in the
62
V. Bhat et al. / Clinica Chimica Acta 446 (2015) 61–63
form of differential leukocyte count with count of immature cells, if any and important features of RBC morphology. The laboratories were offered the choice of reporting the diagnosis based on these findings. The reticulocyte count was reported in percentages. The reports were sent to the assessing laboratory by courier before the given deadline. The results of the cycle were received with the next set of samples. Results were received in the form of Z-score (standard deviation index = SDI) which is defined as the difference between the lab result and group mean in terms of the number of standard deviations from the overall mean. It is given as assessment score for the results among the laboratories (EQA) and within the laboratory (IQA). It is interpreted as Z score: ±0–2 = satisfactory, ±2–3 = borderline, and ≥3 = unsatisfactory. For these assessment results, trend analysis was also performed. For clinical chemistry, lyophilized samples were received as a lot for each year. They were processed on Siemens Dimension Xpand and RXL analyzers which were newly placed in the laboratory and EQAS was part of their verification study. Every month, the designated sample was reconstituted as per the manufacturer's guidelines and processed along with patient samples for 18 routine chemistry parameters. Excess sample was aliquoted in Eppendorf tubes and preserved at −20 °C for any further use. Reports were submitted online through the software provided by the EQAS. The assessment results of the sample were received in about 3–4 working days after the last date of submission of results online. Results were reported as Z score (SDI) and interpreted as 0 = perfect comparison with the consensus group, b 1.25 = acceptable, 1.25–1.49 = acceptable but is under observation, 1.5–1.99 = marginal, performance, evaluate and keep under observation, corrective action if indicated, N2 = unacceptable, corrective action required. For microbiology, EQAS samples were received 4 times a year. Lyophilized isolates of pathogenic bacteria were sent which were reconstituted as per instructions and then processed for culture and antibiotic susceptibility along with routine samples. They were from specimen sources such as pus, sputum, urine, feces and body fluids like CSF. Readily prepared heat-fixed slides were provided for staining procedures like Gram stain, AFB stain etc. All tests were performed as per the standard operating procedures of the laboratory. CLSI guidelines are followed for reporting the antibiotic susceptibility tests [4]. Serum testing for HIV, HBsAg, and HCV formed the serology component of the package. Results were communicated to the proficiency test (PT) provider by post and/or email. 3. Results and discussion In hematology (Table 1), no outliers were noted for reticulocyte and peripheral smear examination. Only one outlier was noted for CBC. Upon analysis, the cause for the outlier was diagnosed as suspect integrity of the sample. It was noticed by the hemoglobin and hematocrit mismatch; the EQAS provider was informed about it. In clinical chemistry (Table 1), outliers (SDI ≥ 2) were noted in 7 samples out of a total of 36 processed. In each sample 21 parameters
were included, so in total 756 parameters were studied out of which in 23 parameters outliers were noticed. Thirteen parameters were analyzed as random errors, 3 transcription errors and seven were systemic errors. The first instance of transcriptional error from the laboratory side was due to incorrect selection of units of measurement. In the second instance, the mistake was due to a personal error, where the decimal point was entered wrongly. Upon correction, both results were found to be within prescribed limits. The third instance of transcriptional error was noted on part of the EQAS provider where test code for the parameter was entered incorrectly and the same was conveyed to them. Of the systemic problems encountered, temperature calibration was needed to correct one error, which helped technologists understand the new equipments Dimension RXL and Xpand better. Additional training sessions were conducted for the laboratory staff to understand the regular maintenance and upkeep as well as mechanical functioning of the equipment better. Training sessions for root cause analysis of the outliers and steps to help prevent such errors in future were held. It included cross-check for quality of water (pH), reagents, equipment, environment and man-power. For reagents, internal quality control data (IQC) as well as calibration logs were studied. Temperature for the storage of reagents was monitored. Equipment quality checks included maintenance logs, temperature logs and events of electrical voltage fluctuation. Temperature and humidity logs for working areas were checked to rule out environmental factors. To prevent further transcription errors, two staffs were deputed to cross-check the data and ensure that no transcriptional errors occur. A sample reconstitution log was maintained to avoid any error during reconstitution. All the relevant data was analyzed from various logs maintained. The abovementioned tools help to perform risk identification in our laboratory and are summarized in the Fishbone/Ishikawa diagram (Fig. 1). In microbiology, some discrepancy was noted in the grading of smears for AFB by Ziehl Neelsen stain (WHO-IUATLD grading), in one instance a grading of 3+ was reported as 2+. There is some potential for variation because the portion of specimen picked for making and spreading the smear may somewhat vary. It is also important to note the presence of polymorphonuclear cells, epithelial cells, RBCs and other significant findings in the Gram stain. Quality of slides with respect to bacterial morphology and staining properties was good but sometimes they may show degenerated cells which are difficult to identify. A discrepancy in the identification of the sent isolate was once noted (Stenotrophomonas maltophilia isolate identified as Burkholderia spp.) This may arise due to differences in methods used for identification viz manually performed biochemical tests versus automated methods. Due to the wide array of biochemical reactions that need to be performed for accurate identification, with various factors affecting the reactions, the results of manual and automated ID may not accurately match in 100% of isolates, as seen occasionally in Gram negative nonfermenters. No discrepancy was noted in any serological results. Also, only rarely were any discrepancies noted in the antibiotic susceptibility results. There were instances of minor discrepancies — not impacting the interpretation with respect to susceptibility of the isolate.
Table 1 Type and percentage of errors noted. Section
Tests
No. of EQA cycles
Hematology
Reticulocyte count and peripheral blood smear examination CBC Various biochemical analytes (total 21)
2 cycles (4 samples in each cycle)
Clinical chemistry
(2 cycle dimension Xpand + 1 cycle dimension RXL) 12 samples in each cycle and 21 parameters in each sample
Total number of parameters analyzed
36 EQAS samples tested for 21 parameters each Total =756
No. of errors
Type of errors
% error in relation to parameters
None
NA
0
1 7 EQAS samples (23 parameters)
Sample integrity Random (13 parameters) Transcriptional (3 parameters) Systemic (7 parameters)
0 1.719 0.396 0.925
V. Bhat et al. / Clinica Chimica Acta 446 (2015) 61–63
63
Fig. 1. Steps for identification of potential errors in processing samples. IOC: internal quality control, EQAS: External Quality Assurance Scheme.
EQAS and internal quality control (IQC) are 2 mainstays for sustaining quality in any diagnostic laboratory. While EQAS gives us a good overview of the accuracy and standardization of the test results for the parameters tested [5], IQC helps us in evaluating precision. Together these assessment schemes help diagnose and differentiate between systemic and random errors. In our study no incidence of any discrepancy between the results of EQAS and IQC was not noted. Root cause analysis is done for each outlier for the possible reasons. It includes reviews of the IQC results for the parameter, reviewing the process of EQAS sample processing and reporting, reviews of the maintenance of the equipment, review of the consumables and reagents used for processing and checks for transcriptional errors if any. 4. Conclusion On the whole the EQAS experience for our diagnostic laboratories was satisfying. It helped us in understanding our shortcomings in our processes and overcome them and instilled confidence in the laboratory
staff. EQAS along with IQC is a very important tool for maintaining optimal quality of services.
References [1] Sciacovelli L, Secchiero S, Zardo L, Plebani M. External Quality Assessment Schemes: need for recognised requirements. Clin Chim Acta 2001;309(2):183–99. [2] Taylor A. Quality assessment of measurement — Fourth International Festem Symposium. J Trace Elem Med Biol 2011;25(S1):S17–21. [3] Todd CA, Sanchez AM, Garcia A, Denny TN, Sarzotti-Kelsoe M. Implementation of Good Clinical Laboratory Practice (GCLP) guidelines within the External Quality Assurance Program Oversight Laboratory (EQAPOL). J Immunol Methods 2013. http://dx.doi.org/10.1016/j.jim.2013.09.012 [pii: S0022-1759(13)00268-8. [Epub ahead of print]]. [4] CLSI. Performance standards for Antimicrobial Susceptibility Testing. Twenty-first informational supplement. CLSI document M100-S21. Wayne, PA: Clinical and Laboratory Standards Institute; 2011. [5] Ceriotti F. The role of External Quality Assessment Schemes in monitoring and improving the standardization process. Clin Chim Acta Jan 2 2014. http://dx.doi.org/ 10.1016/j.cca.2013.12.032 [pii: S0009-8981(13)00527-5. [Epub ahead of print]].
Contents lists available at ScienceDirect
Clinica Chimica Acta journal homepage: www.elsevier.com/locate/clinchim
Case report
The External Quality Assessment Scheme (EQAS): Experiences of a medium sized accredited laboratory Vivek Bhat ⁎,1, Preeti Chavan 1, Chital Naresh 1, Pratik Poladia 1 Advanced Center for Treatment Research and Education in Cancer, Tata Hospital, Kharghar, Navi Mumbai, India
a r t i c l e
i n f o
Article history: Received 14 January 2015 Received in revised form 3 April 2015 Accepted 6 April 2015 Available online 14 April 2015 Keywords: Quality Assessment Laboratory
a b s t r a c t Introduction: We put forth our experiences of EQAS, analyzed the result discrepancies, reviewed the corrective actions and also put forth strategies for risk identification and prevention of potential errors in a medical laboratory. Methods: For hematology, EQAS samples – blood, peripheral and reticulocyte smears – were received quarterly every year. All the blood samples were processed on HMX hematology analyzer by Beckman-Coulter. For clinical chemistry, lyophilized samples were received and were processed on Siemens Dimension Xpand and RXL analyzers. For microbiology, EQAS samples were received quarterly every year as lyophilized strains along with smears and serological samples. Results: In hematology no outliers were noted for reticulocyte and peripheral smear examination. Only one outlier was noted for CBC. In clinical chemistry outliers (SDI ≥ 2) were noted in 7 samples (23 parameters) out of total 36 samples (756 parameters) processed. Thirteen of these parameters were analyzed as random errors, 3 as transcriptional errors and seven instances of systemic error were noted. In microbiology, one discrepancy was noted in isolate identification and in the grading of smears for AFB by Ziehl Neelsen stain. Conclusion: EQAS along with IQC is a very important tool for maintaining optimal quality of services. © 2015 Elsevier B.V. All rights reserved.
1. Introduction For any clinical laboratory wishing to improve its quality standards and provide the best possible results, participation in an External Quality Assessment Scheme (EQAS) is an important activity towards achieving the same [1]. EQAS helps the laboratories assess their accuracy as well as bias of their results and stability of methods over a longer period of time [2]. It serves as an educational tool by identifying staff training needs and helps to monitor and improve the performance of the laboratory by providing early warning for systematic problems associated with the respective methods. It also provides assurance to consumers (physician and patients), that the laboratory results are reliable by establishing objective evidence of testing quality [3]. Participation in EQAS is mandatory for accreditation and they complement each other dynamically to ensure high quality standards. Eventually, a satisfactory EQAS result will ensure that all the requirements of the accreditation standards are met. At our center, the diagnostic laboratories are accredited by the National Accreditation Board for Testing and Calibration Laboratories (NABL). The hematology, clinical chemistry, and microbiology ⁎ Corresponding author at: Department of Microbiology, Advanced Centre for Training, Research and Education in Cancer (ACTREC), Kharghar, Navi Mumbai- 410210, India. E-mail address: [email protected] (V. Bhat). 1 Tel.: +91 2227405093, +91 9867793325 (mobile).
http://dx.doi.org/10.1016/j.cca.2015.04.007 0009-8981/© 2015 Elsevier B.V. All rights reserved.
laboratories participate in their respective EQAS programs. The hematology laboratory participates in an EQAS program (ISHTMAIIMS EQAP) conducted by All India Institute of Medical Sciences (AIIMS), New Delhi, India. The Clinical chemistry laboratory participates in monthly clinical chemistry program conducted by BIO-RAD (Accredited to ISO/IEC 17043:2010) in which more than two hundred and fifty laboratories participate. The peer groups are divided depending on the equipment and method of tests employed for the particular parameter. The microbiology laboratory participates in the EQAS provided by Indian Association of Medical Microbiologists (IAMM). In this study, we have attempted to put forth our experiences of EQAS, analyzed the result discrepancies, reviewed the corrective actions and also put forth strategies for risk identification and prevention of potential errors in a medical laboratory. 2. Materials and methods For hematology, EQAS samples – blood, peripheral and reticulocyte smears – were received quarterly for the review period of 2011–2013. All the blood samples were processed on HMX hematology analyzer by Beckman-Coulter in duplicate as recommended by the provider and values reported for WBC, RBC, hemoglobin, MCV, MCH, MCHC and platelet counts. Peripheral smears were received with a brief relevant history about the case and significant laboratory findings like Hb, WBC, and platelet count. Participants had to submit their results in the
62
V. Bhat et al. / Clinica Chimica Acta 446 (2015) 61–63
form of differential leukocyte count with count of immature cells, if any and important features of RBC morphology. The laboratories were offered the choice of reporting the diagnosis based on these findings. The reticulocyte count was reported in percentages. The reports were sent to the assessing laboratory by courier before the given deadline. The results of the cycle were received with the next set of samples. Results were received in the form of Z-score (standard deviation index = SDI) which is defined as the difference between the lab result and group mean in terms of the number of standard deviations from the overall mean. It is given as assessment score for the results among the laboratories (EQA) and within the laboratory (IQA). It is interpreted as Z score: ±0–2 = satisfactory, ±2–3 = borderline, and ≥3 = unsatisfactory. For these assessment results, trend analysis was also performed. For clinical chemistry, lyophilized samples were received as a lot for each year. They were processed on Siemens Dimension Xpand and RXL analyzers which were newly placed in the laboratory and EQAS was part of their verification study. Every month, the designated sample was reconstituted as per the manufacturer's guidelines and processed along with patient samples for 18 routine chemistry parameters. Excess sample was aliquoted in Eppendorf tubes and preserved at −20 °C for any further use. Reports were submitted online through the software provided by the EQAS. The assessment results of the sample were received in about 3–4 working days after the last date of submission of results online. Results were reported as Z score (SDI) and interpreted as 0 = perfect comparison with the consensus group, b 1.25 = acceptable, 1.25–1.49 = acceptable but is under observation, 1.5–1.99 = marginal, performance, evaluate and keep under observation, corrective action if indicated, N2 = unacceptable, corrective action required. For microbiology, EQAS samples were received 4 times a year. Lyophilized isolates of pathogenic bacteria were sent which were reconstituted as per instructions and then processed for culture and antibiotic susceptibility along with routine samples. They were from specimen sources such as pus, sputum, urine, feces and body fluids like CSF. Readily prepared heat-fixed slides were provided for staining procedures like Gram stain, AFB stain etc. All tests were performed as per the standard operating procedures of the laboratory. CLSI guidelines are followed for reporting the antibiotic susceptibility tests [4]. Serum testing for HIV, HBsAg, and HCV formed the serology component of the package. Results were communicated to the proficiency test (PT) provider by post and/or email. 3. Results and discussion In hematology (Table 1), no outliers were noted for reticulocyte and peripheral smear examination. Only one outlier was noted for CBC. Upon analysis, the cause for the outlier was diagnosed as suspect integrity of the sample. It was noticed by the hemoglobin and hematocrit mismatch; the EQAS provider was informed about it. In clinical chemistry (Table 1), outliers (SDI ≥ 2) were noted in 7 samples out of a total of 36 processed. In each sample 21 parameters
were included, so in total 756 parameters were studied out of which in 23 parameters outliers were noticed. Thirteen parameters were analyzed as random errors, 3 transcription errors and seven were systemic errors. The first instance of transcriptional error from the laboratory side was due to incorrect selection of units of measurement. In the second instance, the mistake was due to a personal error, where the decimal point was entered wrongly. Upon correction, both results were found to be within prescribed limits. The third instance of transcriptional error was noted on part of the EQAS provider where test code for the parameter was entered incorrectly and the same was conveyed to them. Of the systemic problems encountered, temperature calibration was needed to correct one error, which helped technologists understand the new equipments Dimension RXL and Xpand better. Additional training sessions were conducted for the laboratory staff to understand the regular maintenance and upkeep as well as mechanical functioning of the equipment better. Training sessions for root cause analysis of the outliers and steps to help prevent such errors in future were held. It included cross-check for quality of water (pH), reagents, equipment, environment and man-power. For reagents, internal quality control data (IQC) as well as calibration logs were studied. Temperature for the storage of reagents was monitored. Equipment quality checks included maintenance logs, temperature logs and events of electrical voltage fluctuation. Temperature and humidity logs for working areas were checked to rule out environmental factors. To prevent further transcription errors, two staffs were deputed to cross-check the data and ensure that no transcriptional errors occur. A sample reconstitution log was maintained to avoid any error during reconstitution. All the relevant data was analyzed from various logs maintained. The abovementioned tools help to perform risk identification in our laboratory and are summarized in the Fishbone/Ishikawa diagram (Fig. 1). In microbiology, some discrepancy was noted in the grading of smears for AFB by Ziehl Neelsen stain (WHO-IUATLD grading), in one instance a grading of 3+ was reported as 2+. There is some potential for variation because the portion of specimen picked for making and spreading the smear may somewhat vary. It is also important to note the presence of polymorphonuclear cells, epithelial cells, RBCs and other significant findings in the Gram stain. Quality of slides with respect to bacterial morphology and staining properties was good but sometimes they may show degenerated cells which are difficult to identify. A discrepancy in the identification of the sent isolate was once noted (Stenotrophomonas maltophilia isolate identified as Burkholderia spp.) This may arise due to differences in methods used for identification viz manually performed biochemical tests versus automated methods. Due to the wide array of biochemical reactions that need to be performed for accurate identification, with various factors affecting the reactions, the results of manual and automated ID may not accurately match in 100% of isolates, as seen occasionally in Gram negative nonfermenters. No discrepancy was noted in any serological results. Also, only rarely were any discrepancies noted in the antibiotic susceptibility results. There were instances of minor discrepancies — not impacting the interpretation with respect to susceptibility of the isolate.
Table 1 Type and percentage of errors noted. Section
Tests
No. of EQA cycles
Hematology
Reticulocyte count and peripheral blood smear examination CBC Various biochemical analytes (total 21)
2 cycles (4 samples in each cycle)
Clinical chemistry
(2 cycle dimension Xpand + 1 cycle dimension RXL) 12 samples in each cycle and 21 parameters in each sample
Total number of parameters analyzed
36 EQAS samples tested for 21 parameters each Total =756
No. of errors
Type of errors
% error in relation to parameters
None
NA
0
1 7 EQAS samples (23 parameters)
Sample integrity Random (13 parameters) Transcriptional (3 parameters) Systemic (7 parameters)
0 1.719 0.396 0.925
V. Bhat et al. / Clinica Chimica Acta 446 (2015) 61–63
63
Fig. 1. Steps for identification of potential errors in processing samples. IOC: internal quality control, EQAS: External Quality Assurance Scheme.
EQAS and internal quality control (IQC) are 2 mainstays for sustaining quality in any diagnostic laboratory. While EQAS gives us a good overview of the accuracy and standardization of the test results for the parameters tested [5], IQC helps us in evaluating precision. Together these assessment schemes help diagnose and differentiate between systemic and random errors. In our study no incidence of any discrepancy between the results of EQAS and IQC was not noted. Root cause analysis is done for each outlier for the possible reasons. It includes reviews of the IQC results for the parameter, reviewing the process of EQAS sample processing and reporting, reviews of the maintenance of the equipment, review of the consumables and reagents used for processing and checks for transcriptional errors if any. 4. Conclusion On the whole the EQAS experience for our diagnostic laboratories was satisfying. It helped us in understanding our shortcomings in our processes and overcome them and instilled confidence in the laboratory
staff. EQAS along with IQC is a very important tool for maintaining optimal quality of services.
References [1] Sciacovelli L, Secchiero S, Zardo L, Plebani M. External Quality Assessment Schemes: need for recognised requirements. Clin Chim Acta 2001;309(2):183–99. [2] Taylor A. Quality assessment of measurement — Fourth International Festem Symposium. J Trace Elem Med Biol 2011;25(S1):S17–21. [3] Todd CA, Sanchez AM, Garcia A, Denny TN, Sarzotti-Kelsoe M. Implementation of Good Clinical Laboratory Practice (GCLP) guidelines within the External Quality Assurance Program Oversight Laboratory (EQAPOL). J Immunol Methods 2013. http://dx.doi.org/10.1016/j.jim.2013.09.012 [pii: S0022-1759(13)00268-8. [Epub ahead of print]]. [4] CLSI. Performance standards for Antimicrobial Susceptibility Testing. Twenty-first informational supplement. CLSI document M100-S21. Wayne, PA: Clinical and Laboratory Standards Institute; 2011. [5] Ceriotti F. The role of External Quality Assessment Schemes in monitoring and improving the standardization process. Clin Chim Acta Jan 2 2014. http://dx.doi.org/ 10.1016/j.cca.2013.12.032 [pii: S0009-8981(13)00527-5. [Epub ahead of print]].
