The Impact of Clinical Laboratory Improvement Advisory Committee Recommendations on Microbiology Laboratories

The Clinical Laboratory Improvement Advisory Committee (CLIAC) was mandated by the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and established in 1992 to provide advice to the Department of Health and Human Services on regulation of laboratory testing and improving laboratory quality. Since then, CLIAC has met regularly and recommended regulatory changes to CLIA, provided input on good laboratory practices, and discussed critical issues related to clinical and public health testing, the laboratory workforce, and laboratory systems research. The Committee has been effective in driving changes to microbiology quality control, which have led to a decreased burden and lower laboratory costs without sacrificing quality. The issues CLIAC addresses are complex and sometimes controversial, yet members have said their time on the Committee is worthwhile and that CLIAC has a positive influence on laboratory medicine. This Committee will remain a vital resource for providing guidance as laboratory testing continues to evolve.     

Achieving quality reproducible results and maintaining compliance in molecular diagnostic testing of human papillomavirus

Laboratories contemplating either the addition of new molecular tests or modifying methods approved by the Food and Drug Administration for human papillomavirus testing should be aware of a variety of procedural, performance, and regulatory issues surrounding such activity. Diagnostic medical laboratory testing in the United States is regulated by the Centers for Medicare and Medicaid Services, an agency formerly known as the Health Care Finance Administration. The regulatory vehicle of the Centers for Medicare and Medicaid Services is manifested in the Clinical Laboratory Improvement Amendments (CLIA). The CLIA program has put into place specific regulations for laboratory quality control, which includes specific recommendations for method validation. Regulations that must be followed regarding personnel, quality control, quality assurance, method validation, and proficiency testing depend on the complexity category of the individual test. All molecular diagnostic tests, including those for human papillomavirus, are considered high complexity. The Centers for Medicare and Medicaid Services retains the authority to allow private, national accreditation organizations to "deem" that a laboratory is compliant with CLIA '88 requirements. Accreditation organizations, such as the Joint Commission for Accreditation of Hospitals, the Commission on Office Laboratory Accreditation, and the College of American Pathologists (CAP), as well as several state medical laboratory-accrediting agencies, possess the authority to deem laboratories as "CLIA-approved." The CAP, through its Laboratory Accreditation Program, has promoted standards for laboratory performance and method validation. In general, guidelines set forth in the CAP Laboratory Accreditation Program checklists specify that all clinical laboratory testing must essentially meet those requirements defined for high-complexity testing under CLIA '88, including test validation standards, reportable/reference ranges, performance criteria, and proficiency testing.     

Point-of-care prothrombin time measurement for professional and patient self-testing use. A multicenter clinical experience. Oral Anticoagulation Monitoring Study Group

We enrolled 386 subjects in a multicenter study of a point-of-care (POC) prothrombin time (PT) testing device. POC tests were performed by health care professionals using venous and finger-stick specimens and by patients using finger-stick specimens. Venous blood also was analyzed in the local hospital laboratory and a national reference laboratory. Accurate POC results were obtained by professionals using both types of specimens. Patients' results were equivalent to those of professionals. The identification of the patient's therapeutic status based on the International Normalized Ratio (INR) was equivalent for POC and local hospital laboratory PT results; 75% of local laboratory results and 77% of POC results were within 0.4 INR of reference laboratory results, while 93% of either system (POC or local laboratory) were within 0.7 INR. Patients overwhelmingly reported satisfaction with the self-test, including the finger stick and device operation. The INR from the POC device is clinically equivalent to the laboratory INR for assessment of anticoagulation status and management decisions in professional and self-testing environments. Patients can learn to perform accurate PT testing, and POC PT testing is feasible in patients' homes.     

A Side-by-Side Comparison of Clinical versus Current Good Manufacturing Practices (cGMP) Microbiology Laboratory Requirements for Sterility Testing of Cellular and Gene Therapy Products

Over the last few years, there have been numerous discussions on the American Society for Microbiology’s clinical listservs (DivC, and ClinMicroNet) regarding sterility testing of cell and gene therapy products and environmental monitoring and gloved fingertip testing for hospital pharmacies. Clinical microbiology laboratories have often been asked to assist with testing due to the on-site proximity of laboratory equipment and microbiological expertise within the hospital environment. The role of the clinical microbiology laboratory in this setting, however, is questionable due to major differences in test requirements and regulatory oversight. Here, we provide a side-by-side comparison of clinical versus current good manufacturing practices microbiology laboratories to provide guidance to those that are currently assisting with or have been asked to assist with sterility testing of manufactured biopharmaceutical products that have become common frontline treatments in modern medicine.     

Internal validation testing for new technologies: Bringing telecytopathology into the mainstream

Implementing new technology in the laboratory can improve processes and patient care, but compliance with regulatory requirements can be a significant hurdle to clear. This study provides a detailed procedure to address user training, competency assessment, and internal validation of telecytopathology simultaneously, while fulfilling regulatory requirements set forth by the College of American Pathologists and CLIA ‘88. Six pathologists participated in this study. Methods and materials used included a blind correlation study between diagnoses rendered via telecytopathology and via direct microscopy on 10 finalized fine needle aspiration (FNA) cases. The first step of this procedure involved each pathologist to render a diagnosis for each specimen using telecytopathology. The second step was to allow each pathologist to diagnose each specimen via direct microscopic review after a wait period of at least 6 weeks. The diagnoses rendered via telecytopathology were then compared to both the established final diagnoses and the secondary direct microscopic review diagnoses to examine interpathologist and intrapathologist reproducibility with a passing rate of 90% or better. Results of the study yielded an average concordance rate of 96.67% for interpathologist reproducibility and 95% for intrapathologist reproducibility across all participating pathologists. All participants passed the assessment with a rate of 90% or better, proving evidence of competency. This study confirmed user competency and validated telecytopathology as an effective tool for examining and diagnosing cytology FNA specimens remotely. It also satisfied regulatory compliance requirements to ensure high quality of diagnostic testing and patient care. Diagn. Cytopathol. 2015;43:3–7. © 2014 Wiley Periodicals, Inc.     

Quality assurance programs to meet CLIA requirements

CLIA '88 delineates specific quality assurance (QA) practices for cytology laboratories in the United States. In addition, there are general requirements that all types of clinical laboratories must meet to satisfy the CLIA law and regulations. This paper describes the origins and objectives of CLIA and it outlines the major sections of the legislation. To satisfy the regulations, every laboratory must develop its own quality assurance plan that addresses each of the specific conditions and standards. Furthermore, the laboratory must monitor its performance and document that, indeed, the QA systems are operating effectively. The article then describes the quality assurance plan of the Cytology Department of the Wisconsin State Laboratory of Hygiene. The department uses 28 monitors to determine compliance with the criteria and standards and to prevent problems in its day-to-day operation. When standards are not met or are exceeded, action steps are specified. Diagn Cytopathol 1994;11:195–200. © 1994 Wiley-Liss, Inc.     

Brucella abortus RB51 Strain Sent in a Proficiency Testing Panel to Clinical and Public Health Laboratories

In early 2017, a laboratory proficiency testing panel, designed to assess laboratory competency for culture and identification of bacterial organisms, was distributed to clinical and public health microbiology laboratories. The panel included a Brucella abortus RB51 isolate. Although B. abortus RB51 is an attenuated Brucella species strain, it still poses some risk to laboratory personnel, particularly if safety precautions and personal protective equipment are not adequately deployed. The PT event highlighted the challenges that clinical and public health microbiology laboratories face when handling samples that can contain highly transmissible organisms that can lead to laboratory-acquired infections. This review describes the B. abortus RB51 PT event, its associated exposures, and subsequent medical interventions. General considerations for handling Brucella species, including RB51, in the clinical microbiology laboratory are also discussed. Finally, we describe lessons learned from this event, including improving a “culture of safety” in the clinical laboratory.     

Practice patterns of testing waived under the clinical laboratory improvement amendments

OBJECTIVES: To determine operational practices in laboratories operating under a Certificate of Wavier (waived laboratories), or equivalent, under the Clinical Laboratory Improvements Amendments (CLIA) of 1988 when performing tests designated as having an insignificant risk of an erroneous result (ie, waived tests). METHODS: Waived laboratories that were part of the Centers for Disease Control and Prevention Laboratory Sentinel Monitoring Network project in the states of Arkansas, New York, and Washington were surveyed about their quality control (QC) and quality assurances (QA) practices when performing waived testing. Arkansas and Washington sent out similar questionnaires, whereas on-site surveys were conducted in New York. The survey in Arkansas and Washington also included nonwaived laboratories. The New York visits were designed to pilot test a regulatory inspection program for limited testing sites, which, in New York, are roughly equivalent to laboratories operating under a CLIA Certificate of Wavier and/or Provider-Performed Microscopy but are generally not located in physicians' offices. Laboratories visited in New York were selected from a list of limited testing sites and were representative of that population. RESULTS: Arkansas received responses from 211 facilities (37% response rate), of which 38% had Certificates of Waiver. Washington received responses from 190 waived laboratories (71% response rate) and from 116 nonwaived laboratories (32% response rate). In New York, 607 of the 2751 limited testing laboratories were visited. Reporting laboratories in all 3 states most frequently performed testing for glucose, urinalysis, urine human chorionic gonadotropin, occult blood, and group A Streptococcus antigen, although other waived tests were performed less frequently. Washington found that 57% of waived laboratories followed manufacturers' QC requirements. Arkansas found that 58% of laboratories doing waived tests that required liquid controls performed these controls, and 59% performing waived testing requiring electronic controls used these controls. In New York, 68% of the laboratories complied with the manufacturer's QC requirements for a variety of tests. Being accredited by an external organization or affiliated with a more complex laboratory improved compliance. Nonwaived laboratories in Washington and Arkansas complied with manufacturer's instructions at a higher rate than did waived laboratories. Similar deficiencies in following CLIA requirements were found in other areas of laboratory operation. CONCLUSIONS: Just more than half of waived laboratories in 3 diverse states follow manufacturer's instructions for recommended QC and QA. These instructions help ensure that the test will produce results that have an insignificant chance of an error. Although we did not study the impact of this and other findings on patient care, the results show that imposing good laboratory practices by regulation alone was insufficient to ensure quality laboratory results in any location evaluated. A system that can continually provide accessible education on laboratory practices, coupled with new thoughts on the regulatory environment, is in order.     

On the American scene: Cytology proficiency testing symposium overview

The current and future status of cytology proficiency testing (PT) was the focus of a symposium held in Atlanta November 16–17, 1993. Sponsoring organizations were the Centers for Disease Control and Prevention (CDC), the College of American Pathologists (CAP), and the Cytopathology Education Consortium [American Society of Clinical Pathologists (ASCP), American Society of Cytology (ASC), American Society of Cytotechnology (ASCT)]. The February 28, 1992 Final Rule implementing CLIA 1988 had specified that laboratories evaluating gynecologic cytology specimens had to be enrolled in an approved PT program by January 1994. A contract request had no responses by the April 1993 deadline, however.     

Validation of Laboratory-Developed Molecular Assays for Infectious Diseases

Summary: Molecular technology has changed the way that clinical laboratories diagnose and manage many infectious diseases. Excellent sensitivity, specificity, and speed have made molecular assays an attractive alternative to culture or enzyme immunoassay methods. Many molecular assays are commercially available and FDA approved. Others, especially those that test for less common analytes, are often laboratory developed. Laboratories also often modify FDA-approved assays to include different extraction systems or additional specimen types. The Clinical Laboratory Improvement Amendments (CLIA) federal regulatory standards require clinical laboratories to establish and document their own performance specifications for laboratory-developed tests to ensure accurate and precise results prior to implementation of the test. The performance characteristics that must be established include accuracy, precision, reportable range, reference interval, analytical sensitivity, and analytical specificity. Clinical laboratories are challenged to understand the requirements and determine the types of experiments and analyses necessary to meet the requirements. A variety of protocols and guidelines are available in various texts and documents. Many of the guidelines are general and more appropriate for assays in chemistry sections of the laboratory but are applied in principle to molecular assays. This review presents information that laboratories may consider in their efforts to meet regulatory requirements.     

Quality control of test systems waived by the Clinical Laboratory Improvement Amendments of 1988. Perceptions and practices

CONTEXT: Recent advances in laboratory testing technology have resulted in a rapidly increasing number of test systems targeted for physician office, point-of-care, and home health care settings. With enhanced error detection mechanisms and unitized reagents, these new systems simplify the testing process and the assessment of analytical test performance. Many also meet the criteria set by the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to qualify as waived test systems, and laboratories using only waived tests are subject to very limited regulatory oversight. OBJECTIVE: To evaluate use patterns and perceptions about quality control requirements with respect to waived testing. DESIGN AND SETTING: Survey of a network of 431 hospital, independent, and physician office laboratories in the US Pacific Northwest. RESULTS: Responding laboratories (n = 221) were taking advantage of the availability of waived tests and using them to make definitive diagnoses. We found considerable differences between quality control practices and the laboratories' perceptions of quality control requirements. Most respondents were performing traditional quality control on waived tests, influenced by their interpretation of regulations, the intended use of the test, and the testing personnel employed. CONCLUSIONS: Technology optimized for alternate quality control can represent an improvement in ease of use while meeting expectations for accuracy and providing relief from regulatory burdens. However, laboratory personnel exhibit confusion in applying new quality control systems.     

三种方法测定肌钙蛋白I分析性能的比较与评价

用化学发光法、胶体金法及胶乳增强免疫比浊法测定60例肌钙蛋白I（cTnI）,评价三种方法的分析性能及测定结果的差异及相关性,以便临床根据需要选择合适的方法测定cTnI。通过本次评价发现,胶体金法及化学发光法与临床诊断有很好的总符合率,且灵敏度、特异性较高,误诊率和漏诊率低。三种检测方法测定结果之间有显著性差异,P〈0.001,两两比较,胶乳法与胶体金法、化学发光法之间有显著性差异,P值均〈0.001;胶体金和化学发光法之间没有显著性差异,P=0.986。胶体金法（Y1）与化学发光法（X）相关性好,Y1=1.20X-0.11,R2=0.933;相关性优于胶乳增强免疫比浊法（Y2）,Y2=3.65X＋0.49,R2=0.892。在分析性能上胶体金法测定cTnI优于胶乳增强免疫比浊法,且与化学发光法有较好的相关性,适用于急诊及床旁检测。     

Clinical Laboratory Improvement Act of 1988. Background and Impact on Anatomic Laboratories

Abstract

The Clinical Laboratory Improvement Act of 1988 was intended to improve the quality of medical laboratories. It includes education requirements for personnel involved in “high complexity testing” who serve the anatomic pathology lab. Many surgical pathology labs rely on histotechnologists and histotechnicians to gross surgical specimens, a time consuming activity. This has helped to expedite turnaround time and has proven cost-effective. CLIA ′88 could change this practice and cause a shortage of qualified laboratory personnel. This report examines the background and possible impact of CLIA ′88. (The J Histotechhnol 20:159 , 1997)     

A View from the Other Side of the Table: Taking Clinical Microbiology Experience to Industry

Clinical microbiology is a dynamic field that offers many licensed professionals rewarding careers that have a direct impact on patient care. Alternative careers include numerous opportunities for bachelors, masters, and doctoral level scientists in the biotechnology industry, which also impacts human health. Understanding if you are interested in an industry position or where you can apply your skill set outside the routine laboratory is important for deciding a future career path. This article explores the diagnostic life cycle of a commercial product and its stakeholders, as well as providing insight into some of the roles a career in industry can offer those looking to take their clinical microbiology experience outside the clinical laboratory.     

What should a laboratory physician expect from a microbiology laboratory?

Remarkable changes are affecting the discipline of Clinical Pathology/Laboratory Medicine in Japan. Laboratories are changing from revenue centers to cost centers that have many serious problems(ex. closure of the clinical laboratories in the hospitals and outsourcing of laboratory tests due to restructuring in response to economic aspect, limited numbers of certified laboratory physicians, and other factors). And many clinicians in university hospitals do not know what they should expect correctly from the microbiology laboratory. Therefore, we, laboratory physicians and medical technologists must modify our behavior effectively and establish a good collaborative partnership with physicians, nurses and other health care professionals. The microbiology laboratory should provide information that will affect clinical management guidelines for obtaining specimens, microbial identification, antimicrobial susceptibilities, reporting of data and educational updating. Leadership and management skills must be increasingly critical to the success of laboratory physicians in and outside of academic centers.     

Common diagnostic tests under the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) in the United States

The lower quality of laboratory testing in unlicensed physicians' office laboratories(POLs) had led to legislation of the Clinical Laboratory Improvement Amendments of 1988(CLIA '88) in the United States. This legislation extended laboratory regulations for quality control and assurance, personnel qualification, record-keeping, and proficiency testing to all laboratories regardless of size, complexity, or location, including POLs and ancillary testing sites in a hospital. According to the implementation of the CLIA '88 in 1992, all testing sites in this country must have inspections and a certificate issued by the federal government. The CLIA '88 has improved the quality of testing in POLs, forcing office physicians to deal with the problem of laboratory quality management, thereby increasing laboratory costs. Thus, compliance with the CLIA '88 standards is expensive. On-site testing in POLs has been reduced, discontinued, or changed as a result of the CLIA '88 legislation. A number of POLs have closed, and physicians have restricted test menus to those with simpler methodology(waived tests) because waiver laboratories do not require inspections by the government. Large portion of laboratory tests, which were formerly done in POLs, flow into the reference laboratory market as outreach tests. Currently, 77% of POLs are performing only waived tests or tests in the provider-performed microscopy procedures category, while only 23% have a certificate for moderate or high complexity methodology status. Thus, common diagnostic tests performed in POLs are predominantly based on the waived tests, which are largely different from those performed in Japan, with respect to test item and methodology.     

Centralization versus Decentralization of Clinical Microbiology Laboratory Services: One More Choice To Make During a Global Pandemic

The delivery of diagnostic laboratory services has undergone significant change in recent years. Specifically, clinical microbiology laboratories are being asked to become more efficient and to utilize health care dollars more effectively while still providing the highest level of care for patients and meeting the needs of health care providers. In some cases, this has led to the need to centralize and consolidate the clinical microbiology laboratory. Here, we discuss the key points to consider surrounding centralization and consolidation of microbiology services during these uncertain times, many of which we have encountered ourselves. We present a methodical approach to assess the factors associated with consolidation, including topics related to management of the microbiology laboratory and ensuring that quality patient care stays at the center of the decision-making process, all while maintaining efficiency and compliance with regulatory guidelines.     

Status of the clinical laboratory in the mandatory postgraduate medical training system. (1) Report from a laboratory technologist

According to a new system for postgraduate clinical training, 33 medical trainees have been accepted for the past two years at Osaka General Medical Center. Before practicing clinical medicine in each division by a super-rotated table, orientation is scheduled for 5 days to master the basic systems indispensable to the hospital. In this orientation, training in laboratory medicine is performed for 7 hours (3.5 hours for 2 days). Trainees are divided into 4 groups and learn emergency tests of chemistry, hematology and urinalysis, blood transfusion, physiology and microbiology for 60 min each. Laboratory technologists instruct the trainees to gain the basic skills. The main contents are blood gas measuring in chemistry, sample preparation in hematology and urinalysis, taking each other's ECG, ordering blood products for transfusion, serologic study of infectious diseases, and Gram stain in microbiology. Although it is difficult to find time for routine analysis and instructing trainees in the clinical laboratory, it is a suitable opportunity for revision, also for laboratory technologists, and for communication to discuss clinical matters.     

应用ROC曲线评价化学发光法及酶联免疫法对HCV感染的诊断价值

目的 探讨国内五种主流丙型肝炎病毒抗体(抗-HCV)酶联免疫法(ELISA)试剂与进口化学发光法(CLIA)检测性能的可比性及其对HCV感染的诊断价值.方法 应用CLIA及五种ELISA(编号为A、B、C、D、E),同时检测免疫印迹法(RIBA)确认的抗-HCV阳性、阴性血清样本各68例,应用受试者工作特征曲线(ROC)评价其性能指标.结果 CLIA及A、B、C、D、E五种ELISA试剂ROC曲线下面积(AUC)分别为:0.989、0.784、0.945、0.841、0.890、0.883(P ＜0.05),差异有统计学意义;CLIA的敏感性大于五种ELISA试剂(P＜0.05),差异有统计学意义,差异主要在于CLIA 8＞S/CO值≥1标本的符合率较低;几种试剂间特异性无显著性差异(P=0.75).结论 国内五种主流HCV抗体ELISA试剂与进口CLIA对HCV感染均具有较高的诊断价值,利用CHA高敏感性及ELISA的高特异性联合检测抗-HCV,可提高HCV感染的诊断效率.