Internal Quality Control Program Research Articles

Homogeneity study of the internal quality control sera for immunodiagnosis of HIV/AIDS

Introduction: The present study reports the data from the first homogeneity assessment of samples composing the serum panels produced at the Immunology Center of Instituto Adolfo Lutz, Sao Paulo. These samples have been distributed to the public laboratories and those partaking in the Brazilian Unified Health System, and to the participants in the Internal Quality Control Program for human immunodeficiency virus (HIV) antibody (Ab) testing. Objective: To assess the homogeneity of serum samples in panels from different lots for HIV/acquired immunodeficiency syndrome (AIDS) immunodiagnosis by using the statistical method to ensure quality of the reference material. Method: Sera homogeneity was evaluated by means of enzyme-linked immunoassay/enzyme immunoassay (ELISA/EIA) for detection of HIV Ab, and the one-way analysis of variance was employed for analyzing the data. No statistically significant differences were found among the several serum vials. Conclusion: The sera dispensed in the vials were homogeneous in the respective lots.

Use of rapid molecular test for multidrug-resistant tuberculosis detection among relapse cases in Cote d’Ivoire

Tuberculosis is explicitly recognized as a major global public health problem. In Côte d’Ivoire, relapse cases represent 66.5% of patients eligible for retreatment according to the National Tuberculosis Control Program. This study objective was to detect multidrug-resistance tuberculosis among relapse cases. Patients were recruited in tuberculosis centers in routine. A standardized questioning was administrated. Two sputum samples were collected and transported at Institut Pasteur. Sputum samples were decontaminated by NALC method. The DNA extraction was realized with 500μl of decontaminated sputum sample with smear-positive. MTBDRplus assay version 2.0 was performed according to the manufacturer’s instruction. An internal quality control program with positive and negative controls was implemented for interpretation of results. In total 146 relapse cases with smear positive were studied. Out of selected patients, 130 had received the 2RHZE/4RH regimen and 16, the 2RHZES/1RHZE/5HRE. In group of relapse cases previously treated with 2RHZE/4RH regimen, 40 (31.3%, IC95%: [0.23; 0.39]) had punctual mutations at codon 526 in rpoB gene. Although, in patients under treated with 2RHZES/1RHZE/5HRE, a mutation in rpoB gene was identified in 12 of 16 sputum samples. Thirteen mutations conferring a resistance to Isoniazid were observed of which 9 in katG gene and 4 in katG and promoter region of inhA gene. The comparison (Chi-square with Yates correction) of resistance rates to Rifampin estimated showed a statistically significant difference.Conclusion: Use of a rapid method to detect drug-resistance in recurrent TB cases has permitted to identify patients eligible for first-line drugs or not.

Molecular Detection of Resistance to Rifampin and Isoniazid among Patients Eligible for Retreatment Regimen in Côte d’Ivoire in 2012

Drug-resistant tuberculosis is an important health problem in Cote d’Ivoire. Patients of category I treatment are based on 2RHZE/4RH regimen. For the patients of category II, the 2RHZES/1RHZE/5HRE regimen is systematically initiated. Study objective was to describe the susceptibility profile to Rifampin and Isoniazid among previously treated patients who are eligible for retreatment and who had received the 2RHZES/1RHZE/5HRE regimen in Cote d’Ivoire with a molecular method in 2012. Two sputum samples were collected to each patient recruited in the reference regional centres for tuberculosis. Sputum samples were decontaminated by NALC method. The DNA extraction was realized with 500 μl of decontaminated sputum sample with smear-positive. MTBDRplus assay version 1.0 was performed according to the manufacturer’s instruction. An internal quality control program with positive and negative controls was implemented for interpretation of results. A total of 278 patients were enrolled, 148 (53.2%) were recurrent TB cases, 118 (42.5%) failure cases, and 12 (4.3%) defaulters. From sputum of previously treated patients, mutli-drug resistant tuberculosis was diagnosed for 60 (69.8%, 95% IC, 60% - 80%) treated with the 2RHZE/4RH regimen, 24 (75%, 95% IC, 60% - 90%) with the 2RHZES/1RHZE/5HRE regimen, 60 (41%, 95% IC, 33% - 49%) recurrent TB cases, and 4 (33.3%) defaulters. The comparison of resistance rates to Rifampin estimated from sputum samples in the categories of treatment failures and the recurrence TB cases showed a statistically significant difference. In Cote d’Ivoire, genotype? MTBDRplus assay has permitted to estimate the prevalence of MDR-TB in categories of previously treated patients for tuberculosis.

Abstract P3-08-07: HER2 positive breast carcinomas: trend in evolution between 1998 and 2008 and relationship with clinico-pathological characteristics in a population based study.

Abstract Background: Determination of HER2 status in invasive breast carcinomas is now mandatory for the optimal treatment of the patient. A vast majority of initial published studies described positivity in about 20 to 25 % of breast carcinomas, but the proportion of HER2 positive gene expression in women with breast cancer varies in the literature from 9 to 74%. The population of the tumor analyzed (for example histologic types, stage, age), the type of the assays used and the lack of uniformity or quality controls in detection assays may partly explain these differences. Our study describes the evolution of HER2 positive invasive breast cancer proportions during a period of 10 years and identifies clinical and pathological characteristics of these positive tumors. Methods: Based on the regional, population-based breast cancer registry, we identify 2396 patients diagnosed with invasive breast cancer in the Côte-d'Or department and treated in a single institution between 1998 and 2008. The HER2 status was determined by immunohistochemistry and by fluorescence in situ hybridization by a single team that performed regular internal quality controls and participated to multiannual external international quality control programs. Results: During the 1998–2008 period, 12.8% of invasive breast cancers were identified as HER2 positive, with no trend to annual variations (p = 0.27). During the same period, despite an increase of 45% of the annual diagnosed cancers in the institution, the clinical and pathological characteristics such as age, tumor size, grade, hormonal receptors expression remain stable. We only noticed a slight but significant increase of lobular carcinomas (p = 0.036). In multivariate analysis, HER2 positivity was as expected associated with: hormonal receptor negative status (OR = 1.7 [IC95%: 1.2–2.4], p = 0.0035), metastatic presentation at diagnosis (OR = 2 [IC95%: 1.2–3.4], p = 0.0092), ductal subtype (OR = 1.9 [IC95%: 1.1–3.1], p = 0.0178) and high SRB grade (OR = 2.8 [IC95%: 1.7–4.5] for SBR II, OR = 5.4 [IC95%: 3.2–9.1] for SBR III, p = 0.0035). Conversely, patients older than 75 years presented mostly HER2 negative tumors (OR = 0.5 [IC95%: 0.3–0.8], p < 0.0001). Conclusions: This population based study on HER2 breast cancer status emphasizes that in a population with stable clinical and tumoral characteristics, when standardized and controlled assays are used, the proportion of HER positive tumors remains stable over a large period and is lower than usually reported (12.8%). Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-07.

The use of latex beads in external quality assurance and internal quality control for routine semen analysis

The usefulness of latex beads of defined concentration was assessed as a substitute for sperm in the performance of External Quality Assurance (EQA) and Internal Quality Control (IQC) of semen analysis. Within the EQA programme, mean±SEM bias (%) was significantly reduced in 2007 compared to 2002 for both specialist (6.0%±5.4% vs. 55.0%±5.9%) and non-specialist (18.4%±5.9% vs. 90.9%±13.4%) laboratories (both p<0.0001), indicating improved accuracy over time. Within the IQC programme, the beads were used in the appraisal of two scientists, one experienced and one inexperienced, against a known standard. Beads were also used to calibrate eleven counting chambers, resulting in one old chamber being discarded due to its poor performance. The present study has shown that the use of a defined concentration of beads is an excellent adjunct to IQC and EQA programmes enabling the performance of both people and equipment to be assessed in an objective manner.

Expect for the Pharmacist in the Management of Infectious Diseases

In the 21 century, the management of infectious diseases has become increasingly important. Especially, the establishment of the infection prevention and control system is very important in the healthcare-settings for patient safety. And from this background, infection control teams (ICT) which perform the infectious diseases management have been organized in many institutions. These ICT members are medical doctors, nurses, medical technologists and pharmacists and the role of the pharmacist in the ICT is very important. The pharmacist should play a role as a specialist for antimicrobial agents, antiseptics and disinfectants. The roles and responsibilities of the pharmacist for infection control are leading the antimicrobial stewardship, promoting the appropriate and rational use of antimicrobial agents, advising the health system on the selection and use of appropriate antiseptics, disinfectants and sterilants, developing guidelines for risk assessment, treatment, and monitoring of patients and health care workers. Establishing internal pharmacy policies, procedures and quality control programs to prevent contamination, educating health professionals, patients, and the public activity are also included. It is expected that the infection control pharmacist should contribute to the management of infectious diseases and patient safety in the healthcare-settings.

Les contrôles de qualité en mycologie médicale

The Quality Management System in medical mycology refers to the systematic monitoring with internal and external quality controls: it needs to be organized in the laboratory. ISO 15189 standard is not precise in how to demonstrate the correctness of tests, in terms of frequency and requirements for quality controls QC. That's why the COFRAC, the French Accreditation Committee has published guides to which we should refer. The laboratory has to apply internal Quality Control Programs. They consist of various tests to check the reagents including the culture media. Reference strains have to be provided and preparations of homemade reagents are needed, because few are commercialized. Maintaining the competence of the technical staff through identification of unknown strains is also required. In the fungal serology field, home made antibodies with pooled sera or antigen controls are needed. This monitoring has to follow the recommandations from the Cofrac technical guide LAB GTA 06. For quantitative analysis, the Levey-Jennings chart is a graph with quality control data plotted on to give a visual indication. Some external QC references, besides the national quality control AFSSAPS, are available. Data evaluation, corrective actions in case of out of range results and preventive actions have to be determined in the Quality System documents and presented in the annual management review.

Erratum to: National estimates of blood lead, cadmium, and mercury levels in the Korean general adult population

All blood heavy-metal analyses were carried out by Seoul Medical Science Institute (SMSI), a laboratory certified by the Korean Ministry of Health and Welfare. For the internal quality assurance and control program, commercial reference materials were obtained from Bio-RAD (Lyphochek [1] Whole Blood Metals Control), which showed that the coefficients of variation were 8.2% for three blood lead samples (reference values: 8.5, 26.0, and 48.0 lg/dL), 14.5% for three blood cadmium samples (reference values: 0.37, 1.11, and 4.30 lg/L), and 8.3% for three blood mercury samples (reference values: 4.7, 36.8, and 68.7 lg/L).

Errors in medicine and errors in laboratory medicine: what is the difference?

Errors in medicine and errors in laboratory medicine: what is the difference?

Quality Monitoring of HIV-1-Infected and Uninfected Peripheral Blood Mononuclear Cell Samples in a Resource-Limited Setting

Human immunodeficiency virus type 1 (HIV-1) vaccine and natural history studies are critically dependent on the ability to isolate, cryopreserve, and thaw peripheral blood mononuclear cell (PBMC) samples with a high level of quality and reproducibility. Here we characterize the yield, viability, phenotype, and function of PBMC from HIV-1-infected and uninfected Ugandans and describe measures to ascertain reproducibility and sample quality at the sites that perform cryopreservation. We have developed a comprehensive internal quality control program to monitor processing, including components of method validation. Quality indicators for real-time performance assessment included the time from venipuncture to cryopreservation, time for PBMC processing, yield of PBMC from whole blood, and viability of the PBMC before cryopreservation. Immune phenotype analysis indicated lowered B-cell frequencies following processing and cryopreservation for both HIV-1-infected and uninfected subjects (P < 0.007), but all other major lymphocyte subsets were unchanged. Long-term cryopreservation did not impact function, as unstimulated specimens exhibited low background and all specimens responded to staphylococcal enterotoxin B (SEB) by gamma interferon and interleukin-2 production, as measured by intracellular cytokine staining. Samples stored for more than 3 years did not decay with regard to yield or viability, regardless of HIV-1 infection status. These results demonstrate that it is possible to achieve the high level of quality necessary for vaccine trials and natural history studies in a resource-limited setting and provide strategies for laboratories to monitor PBMC processing performance.

Bruk av troponinmålinger i norske sykehus

A highly sensitive troponin T analysis became available in Norway in 2009. The Norwegian Society of Medical Biochemistry believed that a national strategy for implementation of the analysis would ensure a more coherent practice for diagnosing acute myocardial infarction (AMI). 70 laboratories were requested to identify (in a questionnaire) the type of assay used, routines for reporting results of analyses, internal quality control programmes (IQA) and local cut-off values for making the diagnosis AMI. 62 laboratories responded and 57 of these analyzed troponins; 60 % used troponin T and 40 % troponin I. 82 % of laboratories were familiar with the decision limit used for diagnosing AMI at their hospital; 43 % of troponin T laboratories used the cut-off recommended by the Norwegian Society of Cardiology (0.03 microg/l) to diagnose AMI. For the two most used troponin I methods (16 laboratories) eight different cut-off values were reported. 24 % (troponin T) and 35 % (troponin I) of laboratories performed IQA at a concentration similar or lower than the local decision limit used when diagnosing AMI. 73 % (troponin T) and 54 % (troponin I) of laboratories used the lower limit of quantification as the lower cut-off value for reportable results. In Norwegian hospitals, users of the same methods for analysis of troponin have different routines for interpreting, IQA and reporting of results. Patient diagnoses may therefore vary according to the hospital used. The Norwegian Society of Medical Biochemistry has developed recommendations for implementation of troponin analyses in Norwegian laboratories.

An international quality control programme for PRISM chemiluminescent immunoassays in blood service and blood product laboratories

Laboratories screening for blood-borne virus infections in blood and blood products are required by international standards and guidelines to ensure that their testing processes remain within control. An effective means of ensuring this aim is through participation in a quality control programme. Analyses of results from a quality control (QC) programme conducted for the Abbott PRISM (PRISM) assays are reported. Laboratories participating in the National Serology Reference Laboratory, Australia's PRISM QC programme were provided with aliquots of a multimarker QC sample which were tested regularly in each PRISM subchannel. Test results were submitted to a single database using an Internet-based QC monitoring system, EDCNet. The QC test results submitted between 15 October 2001 and 5 March 2006 for each PRISM instrument and each lot of PRISM reagent were analysed to determine the imprecision and bias in each test system. A total of 157,404 test results from approximately 47,000 test runs submitted into the EDCNet database were analysed. Six batches of the multimarker QC samples were tested in 454 PRISM reagent lots. The coefficient of variation of QC sample test results ranged from 9.17 to 15.83%, 8.29 to 9.44%, 10.50 to 15.38% and 7.05 to 10.32% when tested in the PRISM anti-hepatitis C virus, anti-human immunodeficiency virus, anti-human T-cell lymphotrophic virus and hepatitis B surface antigen assays, respectively. Analysis of QC test results reported from testing in the anti-HTLV assay detected one lot of reagent (10572HN00) which was identified to be an outlier using Tukey's filter. Analysis of test results of an external QC sample can be used as a statistical process control through ongoing measurement of imprecision. When laboratories test the same QC sample in the same assay and submit test results to a single database, the results can be compared and a measure of bias can be calculated. The resulting QC programme can offer detection of unexpected variation in the testing processes and the source of variation investigated.

Design, implementation and results of the quality control program for the Australian government's point of care testing in general practice trial

From 2005 to 2007 the Australian Government funded a multicentre, clustered randomized controlled trial to determine the clinical effectiveness, cost-effectiveness, satisfaction and safety of point of care testing (PoCT) in general practice (GP). PoC tests measured (and devices used) in the trial were haemoglobin A1c and urine albumin:creatinine ratio (DCA 2000), lipids (Cholestech LDX) and international normalized ratio (CoaguChek S). An internal quality control (QC) program was developed as part of a quality management framework for the trial. PoCT device operators were provided with a colour-coded QC Result Sheet and QC Action Sheet for on-site recording and interpreting of their results. Within-practice imprecision for QC testing was calculated and compared with the analytical goals for imprecision set prior to the trial. The average participation rate for QC testing was 91% or greater. Median within-practice imprecision met the analytical goals for all PoC tests, except for high-density lipoprotein-cholesterol (HDL-C) where observed performance was outside the minimum goal for one level and one lot number of QC. Most practices achieved the imprecision goals for all analytes, with the principal exception of HDL-C. Results from QC testing indicate that PoCT in the GP trial met the analytical goals set for the trial, with the exception of HDL-C.

Improved accuracy and robustness of NAA results in a large throughput laboratory by systematic evaluation of internal quality control data

The laboratory for INAA in Delft processes several thousands of samples per year for multielement determinations in a variety of matrices. Samples are measured on different spectrometers (using well-type and coaxial detectors), by different persons and using many different analytical protocols. All these results should be consistent with each other with respect to the degree of accuracy, i.e., the combination of trueness and precision. A rigorous internal quality control program has been implemented with automatic on-line evaluation. Annually an additional evaluation of the internal quality control results is carried out using statistical techniques. The Naji-plot approach has proven to be an important graphical tool since it provides direct insight in both trueness and precision. It is demonstrated that the degree of accuracy of the results obtained under the large variety of operational parameters is under constant improvement.

Accreditation of HLA tests and an external quality control program

Objectives Department of Medical Biology, Istanbul Medical Faculty, serves with European Federation of Immunogenetics (EFI) accredited HLA labs for solid organ and bone marrow transplantation facilities both routinely and for research purposes as well as the organization of national and international quality control programs. Design & methods There are 28 HLA tissue typing laboratories in Turkey as of 2008. Department of Medical Biology was determined to be the organizer of ‘National Quality Control Tests for HLA Tissue Typing (NQCT)’ on behalf of Turkish Ministry of Health by the Scientific Committee of Turkish Ministry of Health. NQCT program is performed for the quality assurance of Lymphocyte Cross Match, anti-HLA antibody screening and identification and HLA-A,-B, DR typing by serological and molecular methods. Results and conclusion The first round of NQCT in 2004 included HLA-A,-B typing by serological methods and HLA-DR typing by molecular methods. However, in the following years other tests were also included. The number of participating laboratories was 12 when the program first started and reached 23 by 2008 at the end of fifth round. The discordance rate among the results of the participating laboratories varied from 1.3% to 11.6%. The international quality control program organized by Department of Medical Biology is performed among Balkan Countries, accredited by EFI. This program, which is termed as Balkan External Proficiency Testing (B-EPT), was initiated in 2004 with 11 participants in the first round. The program reached 24 participating laboratories in the fourth round in 2007. This program includes HLA-A,-B,-DR,-DQ tests by molecular and serological methods.

Quality Control in Coagulation Testing

The term "QUALITY CONTROL" in laboratory medicine refers to all the procedures commonly used in clinical laboratories to monitor the routine performance of testing processes, to detect possible errors, and to correct problems before test results are reported. In particular, internal quality control (IQC) and external quality assessment (EQA) programs are used to evaluate and improve quality in laboratory medicine. Laboratory testing is necessary for the diagnosis and treatment of patients with hemostatic disorders. However, whereas the benefits of quality control and quality assessment in hemostasis have been demonstrated many times and are well documented, available scientific evidence is significantly less than that in clinical chemistry and in other fields of laboratory medicine. Currently available data on analytical quality in coagulation testing not only demonstrates that quality is often unsatisfactory, but also highlights the need for more objective establishment of performances goals. This should be useful for better addressing both IQC and EQA programs. New challenges to EQA schemes for coagulation testing derive from the introduction of innovative tests, genetic analysis, and the need to assess not only analytical procedures but also all steps included in the total testing process.

The quality of fiber counts using improved slides with relocatable fields

A parameter based on discrepancies between reported fibers and verified fibers of relocatable slides is shown to be effective in monitoring the quality of airborne fiber counts. Analysts report only the fibers in each field examined. The verified fibers were determined by two experienced analysts, and are here considered as a "true" value. Most of the verified fibers were confirmed by the reported fibers, and the disputed fibers or fiber counting errors were all located and accounted for. In this study, reference (REF) slides were manufactured from proficiency analytical test (PAT) filter samples from the American Industrial Hygiene Association containing chrysotile or amosite. The slides were made using coverglasses bearing a grid pattern to allow accurate re-examinations. These coverglasses are an improved version of those used in previous studies. Seventy-four out of 85 amosite results and 51 out of 60 chrysotile results of REF slides were within their PAT proficiency ranges. When all reported fibers were normalized against their respective verified fibers, the average fiber count was over-estimated for amosite by 38.3% and under-estimated for chrysotile by 30.4%. The error from counting short fibers (sizing-extra) was 82.6% of the extra fibers and accounted for the 38% over-estimation of amosite fibers. For chrysotile fibers, sizing-extra errors were 74.0% of the extra fibers, but by far the larger errors were oversight-missing errors, which were 96.7% of the missing fibers and accounted for the 30% under-estimation of the chrysotile fibers. The discrepancies were found to be linearly related to counting errors as had been noted in a previous study, giving further weight to a proposed score, calculated from the discrepancy parameter (SigmaD(+) + |SigmaD(-)|)/VF(total), for evaluating the proficiencies of analysts. If a proficiency score =60 is selected, 48 out of 85 amosite results and 17 out of 60 chrysotile results satisfied this criterion in this study. The number of fiber counting errors in this study was larger than could be expected by PAT proficiency criteria. It may be useful to complement existing proficiency test programs with these REF slides. At the end of each proficiency testing round, detailed reports of discrepancies can be provided to participants so that they can improve on their skills in searching and sizing fibers and minimize their counting errors. In addition, the internal quality control program of each laboratory could include counting REF slides regularly by all analysts with control charts of (SigmaD(+)/VF(total)), (SigmaD(-)/VF(total)), (SigmaD(+) + |SigmaD(-)|)/VF(total) and RF(total)/VF(total) maintained to monitor errors, proficiencies and intercounter variations. Ten percent of relocatable slides of routine samples could also be recounted to monitor intracounter variation.

L'accident d'Épinal : passé, présent, avenir

The accident of radiation oncology at the Public General Hospital in Épinal, Vosges, is the highest in France. It is classified level 6 on a 10 degrees scale of the ASN/SFRO ( Autorité de sûreté nucléaire/Société française de radiothérapie oncologique). It is linked to errors in the process of treatment, and a mistake in the use of dynamic wedges, with an overdosage of 20%. The clinical consequences are severe, for the patients treated for a prostate cancer and exposed to this overdosage, between May 2005 and August 2006. Sequelae were classified grade 2 to 5 on the CTCAE 3.0 scale. A second cohort of 397 was identified, which received an overdose of 10% linked to the daily use of portal imaging, which explained a higher risk of gr 2–3 rectitis. The treatments were interrupted in this hospital for several months, to organize a new management of the department, based on quality and safety. The preventive actions to avoid such an accident necessitate to evaluate standard and innovative treatments, to develop an internal and external quality control program.

Guidelines for molecular karyotyping in constitutional genetic diagnosis

Array-based whole genome investigation or molecular karyotyping enables the genome-wide detection of submicroscopic imbalances. Proof-of-principle experiments have demonstrated that molecular karyotyping outperforms conventional karyotyping with regard to detection of chromosomal imbalances. This article identifies areas for which the technology seems matured and areas that require more investigations. Molecular karyotyping should be part of the genetic diagnostic work-up of patients with developmental disorders. For the implementation of the technique for other constitutional indications and in prenatal diagnosis, more research is appropriate. Also, the article aims to provide best practice guidelines for the application of array comparative genomic hybridisation to ensure both technical and clinical quality criteria that will optimise and standardise results and reports in diagnostic laboratories. In short, both the specificity and the sensitivity of the arrays should be evaluated in every laboratory offering the diagnostic test. Internal and external quality control programmes are urgently needed to evaluate and standardise the test results between laboratories.

The effects of analytical factors on second trimester risk estimations

Objective: Triple test with measured maternal serum α-fetoprotein, human chorionic gonadotropin, and unconjugated estriol combination as a routine procedure for fetal Down's syndrome, trisomy 18 and neural tube defect screening has some intrinsic problems, such as precision. The aim of this study was to evaluate the effect of analytical variation of triple test on prenatal risk estimation. Method: Five different serum pools were prepared and triple test was performed seven times for within run and five times for between run precision determination. Result: Within run and between run, precision values of risk estimations by measuring the same sample for Triple test were calculated to be 7.9–21.4% and 14.1–31.0% for trisomy 21, 13.2–23.7% and 14.2–15.1% for trisomy 18, 47.2 and 42.0 % for neural tube defect, respectively. Conclusion: These results demonstrated that analytical variations have great impact on second trimester risk estimation procedures; therefore, triple test analyses should be carried out in laboratories using strict internal and external quality control programs. Moreover, triple test results should always be interpreted by considering analytical and biological variations.