Participation In Quality Assurance Programs Research Articles

A-361 Implementation of a Fit-for-purpose Point of Care Quality Assurance Program

Abstract Background All individuals should have equitable access to accurate and timely testing for infectious diseases. Point of care testing (PoCT) has been developed to support populations having limited access to laboratory-based testing. Unlike laboratory-based testing, PoCT is often performed by non-laboratory staff and outside the jurisdiction of regulatory frameworks. Under these conditions, quality assurance (QA) of PoCT is often lacking; inaccurate testing can go undetected, leading to poor patient outcomes. A fit-for-purpose QA program was developed to monitor the quality of PoCT for infectious disease testing, particularly in low-middle income countries and in testing outside the laboratory regulatory environment. Methods In collaboration with the World Health Organization (WHO), the National Serology Reference Laboratory (NRL) reviewed the barriers to participation in QA programs experienced by PoCT sites. Using this information, NRL developed a QA model specifically designed for PoCT for infectious disease. In collaboration with Foundation for Innovative and New Diagnostics (FIND, Geneva, Switzerland), Kirby Institute (Sydney, Australia) and Flinders University (Adelaide, Australia), NRL implemented the PoCT QA model across Africa, Asia, and remote regional Australia. The model consists of competency panels (CP - one positive and one negative sample) and external quality assessment (EQA) panels. The EQA panels contain five samples. Whereas the test site knows the reactivity of the CP samples, the EQA samples are tested blinded. Both panels use inactivated samples that are stable at ambient temperature. The model uses streamlined logistics channels, with data collection and analysis using smartphone technology and QR codes. NRL designed a method for randomizing the identity of EQA sample vials so test sites can test QA panels ad hoc, and not be limited to specific test event dates. A range of support material such as pictorial instructions for use, virtual training events and on-line videos were produced to support test sites. Results More than 100 test sites from 14 countries have participated in the NRL PoCT QA programs. The model is designed so data is collected by test sites scanning QR codes and entering results directly into a data entry screen. The NRL PoCT QA program removed barriers to participation by offering sample types that are inactivated and stable at ambient temperature for extended periods of time, removing the need for dry ice shipping. The program is cost effective making it accessible to low- and middle-income countries. Data is collected using novel smartphone technology, facilitating results to be entered into a central database for immediate analysis. Testing of the QA samples can be done at any time, avoiding set test events. Conclusion Implementation of a fit-for-purpose PoCT QA for infectious disease testing removes the barriers to participation and facilitates the monitoring of testing over time. Any deficiencies in testing can be detected and addressed rapidly, ensuring that accurate test results are reported, and the population protected.

Deviating HER2 test results in gastric cancer: analysis from the prospective multicenter VARIANZ study

PurposeThe prospective multicenter VARIANZ study aimed to identify resistance biomarkers for HER2-targeted treatment in advanced gastric and esophago-gastric junction cancer (GC, EGJC). HER2 test deviations were found in 90 (22.3%) of 404 cases (central versus local testing) and were associated with negative impact on survival for trastuzumab-treated patients. Here, we investigated methodological and biological variables that may promote deviating HER2 test results.MethodsWe analyzed HER2 testing procedures and participation in quality assurance programs of 105 participating local pathology laboratories. Furthermore, tumor localization and histological subtypes were compared between patients with centrally confirmed (central HER2 + /local HER2 + , n = 68) and unconfirmed HER2 status (central HER2 −/local HER2 + , n = 68).ResultsFor central HER2 testing, concordance between in situ hybridization (ISH) and immunohistochemistry (IHC) was 98.3%, with IHC sensitivity of 93.3% (84 IHC + of 90 ISH +), specificity of 99.5% (389 IHC- of 391 ISH-), and a positive diagnosis rate of 97.7%. Central confirmation of the local HER2 IHC scores were seen for the majority of locally HER2- IHC 0/1 (172/178; 96.6%), but less frequently for locally IHC3 + (57/124; 46.0%) cases. Deviation rate was not associated with IHC antibody platform used in the local pathology institute neither with participation in quality-assuring tests. Regarding tumor characteristics, deviating test results were more frequently found in GC vs. EGJC (69.1% vs. 39.7%; p = 0.001) and in Laurén diffuse vs. intestinal subtype (23.5% vs. 5.9%, p = 0.004).ConclusionTumor localization and histological subtype have an impact on HER2 test deviation rates. Assessment of HER2 remains challenging for GC and EGJC.

Abstract P2-10-09: The incidence of false negative of HER2/Neu status in primary breast cancer in the era of standardized testing: a Canadian prospective study.

Abstract The efficacy of trastuzumab in the treatment of primary breast cancer has mandated accurate and timely testing of all patients with a new diagnosis of breast cancer. Testing is centralized in designated laboratories across Canada with adherence to guidelines and mandatory participation in quality assurance programs. The Canadian testing algorithm recommends starting with immunohistochemistry (IHC) followed by in situ hybridization (ISH) for equivocal cases. Early HER2 testing showed that approximately 25–30% of invasive breast cancer is HER2 positive. Recent data shows that the HER2/neu positive rate in breast cancer in Canada is 17.6%. Design: The study was designed to assess the rate of false-negative HER2 tests based on the IHC-first algorithm used in 8 pathology centres across Canada. Surgical excisions with invasive carcinoma were tested using the standardized local methodology for both IHC and ISH. The cases were scored by the local breast pathologist and in 2 of 8 centers image analysis was used in the evaluation of ISH. We compared consecutive HER2-negative IHC results (score 0/1+) to the corresponding ISH (either silver or fluorescence) result. False negative cases were defined as a negative IHC with an ISH ratio of≥ 2, since these patients are eligible for trastuzumab therapy. Results: 715 cases were analyzed by IHC using Ventana 4B5 (287), HercepTest (253), or SP3 (175), and by ISH kits: Vysis FISH (303), Ventana SISH (412). The HER2 and CEP17 counts were available in all cases. There were 4 cases with an ISH score ≥2 (4B5: 2/4, HercepTest 1/4, SP3 1/4). In 3 additional cases the absolute HER2 copy number was ≥6 but the HER2/CEP17 amplification ratio was <2 due to an increased number of CEP 17 signal (“polysomy 17”) or amplification of the pericentromeric region. The overall rate of false negative cases was 0.98% (7/715). These cases had a low level of amplification (ratio 2 to 2.45) or an absolute HER2 count of 6–8. Conclusion: Our observation confirms that IHC is an adequate test to predict negative HER2 status in primary breast cancer in surgical excision specimens, even when different antibodies and IHC platforms are used. The study supports and justifies the Canadian algorithm of IHC followed by ISH in equivocal cases in view of the extremely low percentage of false negative cases observed. This reflects the strict adherence to internal protocols and mandatory participation in quality assurance programs. These results provide further confirmation that the vast majority of patients eligible for trastuzumab are not deprived from an effective treatment by using this algorithm. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-09.

Isolation and identification of Burkholderia cepacia by participants in an external Quality Assurance Program (QAP) between 1994 and 1999

External quality assurance programs (QAPs) provide an opportunity to benchmark laboratory performance according to the profile of specimens received. Participant confidentiality is maintained within each group of laboratories whose performance is measured using similar, repetitive exercises. Isolation and identification of Burkholderia cepacia from simulated cystic fibrosis (CF) sputa was a clinically relevant exercise that provided a model for this analytical approach. Between 1994 and 1999, six Royal College of Pathologists of Australasia (RCPA) Microbiology QAPs included four simulated CF sputa and two panels of oxidative Gram-negative bacilli. Laboratories were grouped according to experience with CF sputa disclosed by two questionnaires. Data were analysed by laboratory group for ability to isolate and identify B. cepacia. Three laboratory groups annually received >100 CF sputa (CF>100), 100 CF sputa or fewer, or did not regularly receive CF sputa. CF>100 laboratories inoculated more isolation media, were more likely to use selective media and were less likely to misidentify B. cepacia than the other groups. Improved performance by CF>100 laboratories was marked after the first exercise and remained at a high level compared with the other two groups. This trend in performance was also apparent for Pseudomonas aeruginosa although the numbers of errors were less than for B. cepacia. These exercises demonstrated consistently improved performance only among CF>100 laboratories. The future criteria for laboratory accreditation may include performance as well as participation in QAPs, placing additional burdens on organisers and participants.