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3B Quality Systems in the Clinical Microbiology Laboratory NANCY L. ANDERSON, MICHAEL A. NOBLE, ALICE S. WEISSFELD, AND RONALD J. ZABRANSKY COORDINATING EDITOR

DAVID L. SEWELL

Cumitech CUMULATIVE TECHNIQUES AND PROCEDURES IN CLINICAL MICROBIOLOGY

Cumitech 1C

Blood Cultures IV

Cumitech 2B

Laboratory Diagnosis of Urinary Tract Infections

Cumitech 3B

Quality Systems in the Clinical Microbiology Laboratory

Cumitech 5A

Practical Anaerobic Bacteriology

Cumitech 6A

New Developments in Antimicrobial Agent Susceptibility Testing: a Practical Guide

Cumitech 7B

Lower Respiratory Tract Infections

Cumitech 12A

Laboratory Diagnosis of Bacterial Diarrhea

Cumitech 13A

Laboratory Diagnosis of Ocular Infections

Cumitech 16A

Laboratory Diagnosis of the Mycobacterioses

Cumitech 18A

Laboratory Diagnosis of Hepatitis Viruses

Cumitech 19A

Laboratory Diagnosis of Chlamydia trachomatis Infections

Cumitech 21

Laboratory Diagnosis of Viral Respiratory Disease

Cumitech 23

Infections of the Skin and Subcutaneous Tissues

Cumitech 24

Rapid Detection of Viruses by Immunofluorescence

Cumitech 25

Current Concepts and Approaches to Antimicrobial Agent Susceptibility Testing

Cumitech 26

Laboratory Diagnosis of Viral Infections Producing Enteritis

Cumitech 27

Laboratory Diagnosis of Zoonotic Infections: Bacterial Infections Obtained from Companion and Laboratory Animals

Cumitech 28

Laboratory Diagnosis of Zoonotic Infections: Chlamydial, Fungal, Viral, and Parasitic Infections Obtained from Companion and Laboratory Animals

Cumitech 29

Laboratory Safety in Clinical Microbiology

Cumitech 30A

Selection and Use of Laboratory Procedures for Diagnosis of Parasitic Infections of the Gastrointestinal Tract

Cumitech 31

Verification and Validation of Procedures in the Clinical Microbiology Laboratory

Cumitech 32

Laboratory Diagnosis of Zoonotic Infections: Viral, Rickettsial, and Parasitic Infections Obtained from Food Animals and Wildlife

Cumitech 33

Laboratory Safety, Management, and Diagnosis of Biological Agents Associated with Bioterrorism

Cumitech 34

Laboratory Diagnosis of Mycoplasmal Infections

Cumitech 35

Postmortem Microbiology

Cumitech 36

Biosafety Considerations for Large-Scale Production of Microorganisms

Cumitech 37

Laboratory Diagnosis of Bacterial and Fungal Infections Common to Humans, Livestock, and Wildlife

Cumitech 38

Human Cytomegalovirus

Cumitech 39

Competency Assessment in the Clinical Microbiology Laboratory

Cumitech 40

Packing and Shipping of Diagnostic Specimens and Infectious Substances

Cumitech 41

Detection and Prevention of Clinical Microbiology Laboratory-Associated Errors

Cumitech 42

Infections in Hemopoietic Stem Cell Transplant Recipients

Cumitechs should be cited as follows, e.g.: Anderson, N. L., M. A. Noble, A. S. Weissfeld, and R. J. Zabransky. 2005. Cumitech 3B, Quality Systems in the Clinical Microbiology Laboratory. Coordinating ed., D. L. Sewell. ASM Press, Washington, D.C. Editorial board for ASM Cumitechs: Alice S. Weissfeld, Chair; Maria D. Appleman, Vickie Baselski, B. Kay Buchanan, Mitchell l. Burken, Roberta Carey, Linda Cook, Lynne Garcia, Mark LaRocco, Susan L. Mottice, Michael Saubolle, David L. Sewell, Daniel Shapiro, Susan E. Sharp, James W. Snyder, Allan Truant. Effective as of January 2000, the purpose of the Cumitech series is to provide consensus recommendations regarding the judicious use of clinical microbiology and immunology laboratories and their role in patient care. Each Cumitech is written by a team of clinicians, laboratorians, and other interested stakeholders to provide a broad overview of various aspects of infectious disease testing. These aspects include a discussion of relevant clinical considerations; collection, transport, processing, and interpretive guidelines; the clinical utility of culture-based and non-culture-based methods and emerging technologies; and issues surrounding coding, medical necessity, frequency limits, and reimbursement. The recommendations in Cumitechs do not represent the official views or policies of any third-party payer. Copyright © 2005 ASM Press American Society for Microbiology 1752 N Street NW Washington, DC 20036-2904 All Rights Reserved 10 9 8 7 6 5 4 3 2 1

Quality Systems in the Clinical Microbiology Laboratory Nancy L. Anderson Centers for Disease Control and Prevention, Atlanta, GA 30341–3717

Michael A. Noble Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V5Z 1M9, Canada

Alice S. Weissfeld Microbiology Specialists Incorporated and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77054

Ronald J. Zabransky Cedarburg, WI 53012

COORDINATING EDITOR: David L. Sewell Pathology and Laboratory Medicine Service, Veterans Affairs Medical Center, and Department of Pathology, Oregon Health and Science University, Portland, OR 97239

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2 Regulatory and Accreditation Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3 Quality System Standards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3 Personnel Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6

General Elements of a Quality System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8 Specific Elements of a Quality System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9 Management Responsibility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9 The Laboratory Testing Circle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9 Procedure Manuals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10 Specimen Handling and Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11 Media, Reagents, Stains, Analyte-Specific Reagents (ASRs), and Kits . . . . . . . . . . . . . . . .12 QC Organisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15 Instruments and Equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15 Test and Culture Examination and Organism Identification . . . . . . . . . . . . . . . . . . . . . . . . .15 Antimicrobial Susceptibility Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16 Recording, Interpretation, Reporting, and Record Retention . . . . . . . . . . . . . . . . . . . . . . .17

External Quality Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18 Inspections and Accreditation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19 PT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19 Alternatives to External PT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19 Other Quality Assessment Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .20

Internal Quality Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .20 Quality Indicators . . . . . . Error Detection . . . . . . . . Verification and Validation Audits . . . . . . . . . . . . . . Benchmarking . . . . . . . .

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Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Appendix 1: Websites for CLIA and Quality System Information . . . . Appendix 2: Definitions and Abbreviations . . . . . . . . . . . . . . . . . . . . . Appendix 3: CLIA-Approved Accreditation Organizations . . . . . . . . . . Appendix 4: States That Regulate or License Clinical Laboratories . . Appendix 5: Examples of PT Programs for Microbiology Laboratories

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CUMITECH 3B

Appendix 6: Example of a Self-Evaluation Survey . . . . . . . . . . . . . . . . . . . . .25 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27

INTRODUCTION

T

he history of quality systems in the United States is often cited as originating with the efforts of Walter Shewart and W. Edwards Deming during the period from 1930 through 1950 (93). Shewart, working as a statistician with Bell Telephone Laboratories, developed and introduced techniques of statistical control to monitor and track worker task performance. Deming, through his position with the U.S. Department of Agriculture, expanded upon Shewart’s techniques and introduced teaching methods that widely disseminated the discipline of quality control (QC). Both Shewart and Deming are recognized for introducing the process of continual improvement through the cycle of plan-do-check-act (appropriately referred to as the Shewart cycle or the Deming cycle) (39, 93). Shewart demonstrated the importance of having each worker responsible for monitoring his or her own job performance, and Deming demonstrated that statistical QC without the clear, unambiguous positive pressure of management would inevitably go awry (93). In 1942, with increasing pressure to ensure that wartime suppliers could provide quality materials, the U.S. Department of Defense developed a code of standards. By 1958, this was established as MIL-Q9858a, MIL Specification—Quality Specification. This standard was adopted by the North Atlantic Treaty Organization as Allied Quality Assurance Publication 1 (AQAP-1) and later served as the basis of the commercial quality standard developed by the British Standards Institute, BS 5750, Guidelines for Quality Assurance, and finally as the basis for the International Organization for Standardization (ISO) document ISO 9000:1987. ISO 9000 has been reviewed and revised on two occasions; the most current editions are ISO 9001:2000 and ISO 9004:2000 (4). With respect to laboratories, ISO has developed two important documents linked to, but separate from, ISO 9000 (4). Initially introduced by the International Laboratory Accreditation Conference of 1977, ISO and the International Electrotechnical Commission (IEC) first published Guide 25, General Requirements for the Competence of Laboratories, in 1980. ISO-IEC Guide 25 was a mutually recognized basis for laboratory accreditation. In 1999, it was revised and published as ISO-IEC 17025 (16, 75). In 1996, ISO convened to develop a quality management standard for medical laboratories. This was

published in 2003 as ISO 15189:2003, Medical Laboratories—Particular Requirements for Competence and Quality (35). Internationally, ISO 15189 is becoming, or has become, the basis for medical laboratory quality management throughout Asia, Europe, the Caribbean, Mexico, and Canada. While there is consensus that medical laboratory performance can be enhanced by external audit, either in the form of accreditation or certification, the international community applies the requirement for accreditation differently. In the United States, all clinical laboratories are required to be certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), and accreditation is a voluntary means to meet this federal requirement for certification. A number of national associations and organizations are involved in accreditation of medical laboratories, either in part or in total. Similar to the United States, monitoring of medical laboratories in Canada is under provincial jurisdiction; however, this is not supported by any federal requirement. Of 10 provinces, 6 have active accreditation programs. While each provincial program has its own history and development, supported by two organizations, the Canadian Coalition for Quality in Laboratory Medicine and the National Committee for Medical Laboratory Quality Systems, those with active programs are aligning their programs with the new ISO standard, ISO 15189:2003. In Australia, monitoring of laboratories falls to the National Association of Testing Authorities (NATA). NATA is a government-endorsed provider of accreditation for all laboratories, including, but not limited to, medical laboratories. Prior to ISO 15189:2003, NATA based medical laboratory accreditation upon the ISO standard ISO-IEC 17025:1999, Particular Requirements for Quality and Competence for Calibration and Testing Laboratories. In the European Community, the European Committee for Normalization, or Comité Européen de Normalisation (CEN), is solely responsible for development of accreditation standards, which are applied by individual national accreditation bodies in each country. Under the Vienna Agreement (1991), ISO and CEN are committed to work cooperatively. Documents that are created through the CEN process can be transferred to ISO. In order to facilitate the exchange, the two organizations have agreed that work performed by each should be coordinated and synchronized with the other. Recognizing that many

CUMITECH 3B

Quality Systems in the Clinical Microbiology Laboratory

ISO members are not part of the European Community, CEN also agreed to respond to comments and concerns of non-CEN ISO members. CEN recognizes ISO 15189 as the accreditation standard for medical laboratories. In the United Kingdom, laboratory accreditation is a voluntary rather than a mandated process. When performed, laboratory accreditation is a function of the Clinical Pathology Accreditation UK Ltd. and is aligned with ISO 15189. In addition to accreditation procedures, many medical laboratories in the United States and other countries have also chosen to be voluntarily assessed and to have their quality management systems certified to meet the requirements of the ISO standard ISO 9000:2000 (Quality Management Systems— Fundamentals and Vocabulary). For large service providers and manufacturers with millions of interactions, even 99% compliance with quality measurements is inadequate when one recognizes that each percentage point represents 10,000 noncompliant performances. Based on the standard curve, Motorola initially developed a technique for more precisely monitoring noncompliance and for developing methods to identify projects for determining performance targets. The Six Sigma system provides a mathematical basis to reduce nonconformities to as low as 3.4 per million opportunities (5). Practically, this level of nonconformities would be extremely difficult if not impossible to achieve in the clinical microbiology laboratory. Six Sigma processes have appropriately expanded the Shewart-Deming cycle from the four-phase plan-do-check-act program to five phases (defining, measuring, analysis, improvement, and control) that describe the processes of continual improvement more thoroughly (6). The Six Sigma process first defines the scope of the challenge, establishing the significance, priority, and logistics. Once the challenge is defined, it is then measured or decisions are made with respect to defining the metrics and measurement and the end points for success. The project must be analyzed to determine how it will proceed. The project is not complete until a process follows to implement improvement and control for ongoing continuity.

REGULATORY AND ACCREDITATION ISSUES Quality System Standards Regulatory and voluntary standards outline necessary elements for achieving a quality system in the clinical microbiology laboratory. While regulatory standards generally include minimum requirements for ensuring quality, voluntary standards and guidelines are often consensus standards that represent best practices for clinical laboratories.

3

CLIA Section 353 of the Public Health Service Act (42 U.S.C. 263a), or CLIA, is the amended federal law governing laboratory testing performed in the United States for the diagnosis, prevention, or treatment of disease or assessment of human health (22). By law, any laboratory that tests human specimens for the purposes defined by CLIA must be certified, regardless of the laboratory’s location, size, or type. Requirements for laboratories subject to CLIA were published in the Federal Register on 28 February 1992 as a final rule with comment period (87). The CLIA regulations established uniform minimum standards to ensure the quality of laboratory services based on the complexity of testing performed, with more complicated testing subject to more stringent requirements. There are three categories of testing for CLIA purposes: waived and moderate-complexity (including the provider-performed microscopy procedures [PPMP] subcategory) and high-complexity testing. The 1992 CLIA regulations included provisions for laboratory personnel, facilities, proficiency testing (PT), QC, quality assurance, and record keeping and retention. After publication of the 1992 regulations, laboratories were given time to understand and implement the CLIA requirements. During that time, the U.S. Department of Health and Human Services (HHS) evaluated public comments received in response to the regulations and assessed the impact of CLIA on laboratory testing. In commenting on the regulations, the American Society for Microbiology (ASM) recommended to HHS that the QC testing requirements for microbiology should be based on the performance parameters of reagents or test systems. ASM presented QC testing performance data for 21 commercial microbiology reagents and stains, suggesting that the regulatory frequencies for QC of testing these reagents and stains were excessive, and made several other recommendations about the QC requirements for microbiology (2, 47a). Subsequently, HHS published a revised final rule in the Federal Register on 24 January 2003, which became effective on 24 April 2003 (90). In this rule, HHS responded to numerous comments; clarified the intent of the original regulations; and reorganized the requirements to eliminate redundancy, consolidate similar requirements, and reflect the flow of a patient specimen through the laboratory. This includes receipt of the specimen with the test request through test performance and test result reporting, thus incorporating the quality system concept for laboratory testing. As part of the changes in this final CLIA rule, supported by ASM’s data, the QC testing frequencies for many microbiology reagents and stains were decreased. As mentioned previously, all facilities that perform clinical laboratory testing must be certified under

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CLIA, unless these facilities are located in exempt states having laboratory licensure programs approved by the Centers for Medicare and Medicaid Services (CMS), the HHS agency that administers the CLIA program. To obtain CLIA certification, a laboratory must register with CMS, pay the appropriate fee, and be inspected (routine inspection is not required for waived testing or PPMP). The laboratory’s certificate type depends on the scope and complexity of testing performed. Information on how to apply for a CLIA certificate and the application form may be obtained at http://www.cms.hhs.gov/clia/cliaapp.asp. CLIA-certified laboratories are subject to biennial inspections that are conducted by CMS State Survey Agencies to assess compliance with the regulations. The inspection process is intended to be an educational, outcome-oriented process that provides an opportunity for laboratories to better understand and achieve a quality system and ultimately to improve test results and patient care. Information on CLIA inspections and interpretive guidelines that clarify the CLIA regulations for laboratories were published by CMS (19) and are available on the CLIA website at http://www.cms.hhs.gov/clia/appendc.asp. State Survey Agency websites and CLIA contact information for each state can be found at http://www. cms.hhs. gov/clia/ssa-map.asp. Another route that laboratories may take to meet the CLIA requirements is through accreditation and inspection by a CMS-approved nonprofit organization that has requirements that meet or exceed those of CLIA. Several of these organizations have specific standards for microbiology, blood banking, or histocompatibility laboratories, as well as having general laboratory accreditation standards (80). Appendix 3 lists the CLIA-approved accreditation organizations and identifies those that have approved programs for the specialty of microbiology, including the website addresses for these organizations. A third mechanism for meeting CLIA requirements exists for laboratories in states with CMS-approved licensure programs equivalent to, or stricter than, CLIA. At present, New York and Washington have CLIA-exempt status. Laboratories in these states are exempt from CLIA provided they hold a valid state license. To be licensed, a laboratory must be in compliance with state licensure program requirements as determined by state inspection. Other laboratories for which CLIA is not applicable include forensic and research laboratories and laboratories certified by the Substance Abuse and Mental Health Services Administration. In addition, laboratories under the Departments of Defense and Veterans Affairs are subject to regulations comparable to CLIA and are under the jurisdiction of their respective federal government agencies.

CUMITECH 3B

Other Regulatory Requirements In addition to New York and Washington, many other states and some localities have laboratory requirements for personnel, certain aspects of specimen collection and handling, individual phases of the testing process (including some with specific microbiology requirements), or result reporting (see Appendix 4). Because individual state and local regulations vary and may change over time, laboratories need to be aware of applicable requirements for their state and location. In some cases, it can be confusing for laboratories that are subject to more than one set of requirements, especially when the requirements differ. In such circumstances, laboratories need to be in compliance with the most stringent requirements. It is the responsibility of the laboratory director to be aware of the CLIA requirements, which are minimum regulatory standards, and any applicable accreditation, state, or local requirements. The laboratory director is also responsible for ensuring that the laboratory meets all federal, state, and local requirements for safety, waste disposal, and public health infectious-disease reporting. Voluntary Standards Voluntary consensus standards and professional organizations’ guidelines are also useful in establishing a quality system in the clinical microbiology laboratory. Voluntary standards often represent best practices and may promote higher levels of consistency and quality than minimum regulatory requirements. As previously discussed, international standards for medical laboratories have been developed by ISO and the Clinical and Laboratory Standards Institute (CLSI) (formerly named NCCLS). Both organizations have published comprehensive guidelines for a quality system approach to clinical laboratory testing (35, 66). In some cases, the CLIA regulations defer to specific voluntary standards, including certain CLSI standards for microbiology testing. For example, if a bacteriology laboratory meets the CLSI standards for QC of antimicrobial susceptibility testing (67, 68), under CLIA the laboratory may perform less frequent QC testing than required in the regulations. Likewise, a laboratory using commercially prepared microbiological culture media that are QC tested in accordance with the CLSI standard for media (55) need not perform QC checks specified by CLIA for those media that have been QC tested by the manufacturer. POC and Waived Testing Rapid tests for infectious agents are increasingly becoming available for use as point-of-care (POC) or near-patient tests and are frequently performed in clinics and physician office laboratories and at the patient’s bedside in hospital settings. POC tests are

CUMITECH 3B

Quality Systems in the Clinical Microbiology Laboratory

5

often performed by personnel with limited background and training in laboratory testing (18, 44). Although microscopic examinations are sometimes performed as POC tests, the majority of POC microbiology tests are qualitative immunologic assays (test systems) that are packaged as single units, do not require extensive equipment, and can be performed in 30 min or less using a direct patient specimen. The assays generally detect a specific microbial antigen, antibody, or toxin (18, 44, 92). POC test systems based on nucleic acid testing methodologies are also available for some microorganisms (15, 97), and it is anticipated that additional similar tests will be developed in the future. POC microbiology test systems are usually tests that are waived under the CLIA regulations or categorized as being of moderate complexity. Test systems may be granted CLIA-waived status if they are cleared by the Food and Drug Administration (FDA) for home use or are shown to be simple tests with low risk of an erroneous result (22). The number of waived test systems for an increasing variety of microbial analytes or organisms continues to grow, especially as new rapid tests for infectious agents are cleared or approved by the FDA. A list of microbial analytes for which there are waived test systems available is given in Table 1. The most recent information about CLIA complexity categorizations and waived tests can be obtained via the FDA website at http://www.fda.gov/cdrh/clia/. Laboratories or POC sites performing only waived tests must have a current certificate of waiver but are not subject to inspection or any oversight of this testing other than the requirement to follow the manufacturer’s current test system instructions (87). In addition to the step-by-step instructions for conducting the test, this may include the manufacturer’s instructions for testing internal and/or external controls at a specified frequency and using the test only with specimens identified in the waived-test instructions. Deviation from the manufacturer’s instructions

by a laboratory or a POC testing site would result in loss of waived status for use of the test system in that facility. The modified test would be uncategorized and thus considered high complexity and subject to all requirements for high-complexity testing. It should be noted that accreditation organizations or individual states may not recognize the CLIA-waived status of some or all waived testing or may require oversight of this testing in certain circumstances. For example, the CAP program for POC testing requires that all testing, regardless of the CLIA complexity categorization, be performed in accordance with the quality standards specified by CAP (23). Also, several states have requirements for personnel, PT, test ordering, and results reporting when performing rapid human immunodeficiency virus (HIV) tests that are waived. Once again, each laboratory needs to be aware of current requirements for its state or locality. Facilities performing moderate (or high)-complexity POC tests are responsible for meeting all CLIA requirements applicable to the appropriate category of testing, including personnel, QC, quality assessment, PT, and record keeping. Some microscopic procedures performed as POC tests are in the PPMP subcategory of moderate-complexity testing. This subcategory was established in revisions to the CLIA regulations published in the Federal Register on 19 January 1993 (88) and further revisions published on 24 April 1995 (89). A PPMP certificate permits physicians, midlevel practitioners, and dentists to perform the microscopic procedures that meet criteria for the subcategory (listed in Table 2) and waived tests as part of a patient’s physical examination without being subject to routine inspection. As applicable, the PPMP subcategory is subject to the other CLIA requirements for moderate-complexity testing. Implementation of POC testing can reduce turnaround time for results and allow appropriate and timely antimicrobial therapy, which in turn may reduce the length of stay for hospitalized patients or decrease the need for follow-up visits to physicians

Table 1. Microbial analytes for which there are CLIA-waived test systemsa

Table 2.

Borrelia burgdorferi antibodies Helicobacter pylori H. pylori antibodies HIV-1 antibodies HIV-1/2 antibodies Infectious mononucleosis antibodies Influenza A/B virus Influenza A virus Influenza B virus Respiratory syncytial virus Streptococcus pyogenes Urine catalase

All direct wet-mount preparations for the presence or absence of bacteria, fungi, parasites, and human cellular elements All potassium hydroxide (KOH) preparations Pinworm examinations Fern tests Postcoital direct, qualitative examinations of vaginal or cervical mucus Urine sediment examinations Nasal smears for granulocytes Fecal leukocyte examinations Qualitative semen analysis (limited to the presence or absence of sperm and detection of motility)

a

a

As of February 2005.

PPMPa

See reference 89 for additional information.

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(37, 74). Although testing with single-unit devices may be more expensive than conventional microbiology methods (18), a laboratory should evaluate the total costs of a POC program to determine whether such testing is economically feasible overall in a specific health care setting (32). In addition to cost, when considering POC testing, a laboratory or health care facility should evaluate the need, as well as potential benefits and/or limitations, of POC testing in their setting; appropriate responsibility, oversight, and structure for the testing in that institution; personnel training necessary to accurately conduct the testing and reporting of results; testing methods (including QC); documentation and record keeping; safety; and waste disposal. The CLSI guideline for POC testing provides information and suggestions for each of these issues to promote good laboratory practices and produce reliable test results regardless of where POC testing is performed (57). With respect to CLIA certification, a hospital or other institution that includes a centralized laboratory may conduct POC testing under the certificate of the main laboratory. This may include testing performed at sites within the hospital or other sites at the same physical location or street address. In either case, the laboratory director for the centralized laboratory is responsible for all POC testing sites and must provide oversight of the testing to ensure that (i) testing personnel are trained and demonstrate ongoing competency, (ii) QC and quality assessment activities are conducted and documented, and (iii) results are consistent with results produced in the central laboratory (36, 57). Other CLIA certificate options that laboratories may use when implementing POC or waived testing at more than one location include exceptions for conducting mobile testing or limited public health testing. The mobile-testing exception may be used by laboratories that move among testing sites, such as mobile clinics, health-screening fairs, or other temporary testing locations. In this case, the laboratory may be covered under one certificate at an address designated as the primary site or laboratory location. Mobile vans may provide an unlimited number of waived or moderate- or highcomplexity tests (depending on their certificate type) at an unlimited number of sites, as long as the testing is performed inside the vehicle. The limited public health testing exception allows federal, state, or local public health laboratories that conduct no more than 15 waived and/or moderate-complexity tests per certificate to test under a single laboratory certificate. This testing may be provided at an unlimited number of sites. The tests offered may vary from site to site, as long as they do not include high-complexity procedures or exceed the 15-test total.

CUMITECH 3B

Testing personnel issues are also important considerations for POC testing, from the standpoint of CLIA compliance as well as the quality system concept. Since many of the personnel who perform testing in nontraditional POC settings are not familiar with principles of good laboratory practices, adequate training, ongoing competency assessment of testing personnel, and quality assurance are critical to ensure accurate testing. This is especially important for waived testing, which has no CLIA requirements for personnel and no routine oversight of testing. Personnel Issues Qualifications and Responsibilities (CLIA) Personnel qualifications and responsibilities are contained in Subpart M of the CLIA regulations. The requirements are different for each personnel category and depend on whether the laboratory performs moderate- or high-complexity testing. Table 3 lists the minimum requirements for each type of personnel, as well as their primary responsibilities. In addition to CLIA, laboratories in states with their own personnel requirements must be in compliance with all state (or local) laws. The CLIA qualifications for doctoral-level personnel (e.g., PhD, ScD, DSc, or DrPH) who serve as laboratory directors for high-complexity testing were updated in January 2003 and became effective on 24 February 2003 (90). As of that date, all new directors of high-complexity testing must be certified by an HHS-approved board. The approved boards are listed at http://www.cms.hhs.gov/clia/dirclcon.asp and include the two ASM boards, i.e., the American Board of Medical Microbiology and the American Board of Medical Laboratory Immunology. Doctoral-level (non-MD) directors who are not board certified but were directing (or had directed) high-complexity testing before 24 February 2003 and meet the CLIA requirements for training and experience may continue to serve as laboratory directors under a grandfather clause. Certification and Licensure Certification is a designation of professional status used in many health care professions based primarily on education, experience, and examination. Certification is usually granted by a professional organization. Licensure is a designation of legal status that permits licensees to practice their profession in a given state; thus, a governmental body usually grants licensure. Eleven states (California, Florida, Georgia, Hawaii, Louisiana, Montana, Nevada, North Dakota, Rhode Island, Tennessee, and West Virginia) and one territory (Puerto Rico) have personnel licensure. In all locales but California, national certification [e.g.,

CUMITECH 3B Table 3.

High

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Microbiology personnel requirements and responsibilities under CLIAa

Test complexity level Moderate

Quality Systems in the Clinical Microbiology Laboratory

Personnel Directorb

Must be on site

Minimum qualifications

Technical consultant Clinical consultant

Physician (MD, DO, DDS, DPM) or PhD in science; must have 1 yr of supervisory experience if not a board-certified pathologist or doctoral-level scientist or baccalaureate degree in science plus 2 yr of laboratory training and experience and 2 yr of supervisory experience Baccalaureate degree in science plus 2 yr of experience Physician (MD, DO, DDS, DPM) or boardcertified doctoral-level scientist

Testing personnel

High school diploma plus documentation of on-the-job training

Yes

Directorb

Physician (MD, DO, DDS, DPM) or boardcertified doctoral-level scientist

No

Technical supervisorc General supervisor

No

Clinical consultantc

Baccalaureate degree in science plus 4 yr of experience Associate degree in medical laboratory science plus 2 yr of laboratory experience in high-complexity testing Physician (MD, DO, DDS, DPM) or boardcertified doctoral-level scientist

Testing personnel

Associate degree in medical laboratory technology or laboratory science

Primary responsibilities

No

Overall operation and administration of laboratory, including hiring personnel who are competent to perform testing and report results; responsible for quality of test results

No

Technical and scientific oversight of the laboratory Liaison between clinicians and laboratory; provides consultation regarding appropriate specimens to collect, as well as interpretation of test results Processing patient specimens, performing tests, and reporting results; responsible for quality of test results Overall operation and administration of laboratory, including hiring personnel who are competent to perform testing and report results Technical and scientific oversight of laboratory Day-to-day supervision of laboratory operations and personnel

No

Yes

No

Yes

Liaison between clinicians and laboratory; provides consultation regarding appropriate specimens to collect, as well as interpretation of test results Processing patient specimens, performing tests, and reporting results

a

http://www.phppo.cdc.gov/clia. Must hold state license, if applicable. c May also be director. b

MT (ASCP), M (ASCP), RM (NRM), CLS, and CLS (M)] is recognized as acceptable for state licensure. California laboratorians must still pass the appropriate state examination to be licensed. Studies have shown that certification of laboratory workers correlates with good performance on external proficiency tests (81, 82). It may be assumed that persons with the appropriate educational background and approved technical training will be better prepared to make important interpretive decisions than will untrained persons. The federal government, however, under CLIA (22) relies on outcome measurements, such as performance on proficiency tests and maintenance of a quality assessment program, in place of specific personnel certification or licensure requirements for several clinical laboratory disciplines, including microbiology. Lively and impassioned discussion can be gen-

erated over whether certification of personnel results in better health care delivery. In general, it seems that people with “professional attitudes” tend to seek certification, and it may be that attitude rather than certification itself results in improved performance (1). Competency Assessment CLIA charges both the laboratory director and the technical consultant or supervisor with specific responsibility for ensuring that staff are able to perform test procedures and report test results promptly, accurately, and proficiently (87). Competency assessments are to be made at least semiannually during the first year of employment and annually thereafter unless test methodology or instrumentation changes (27, 31). Assessment of competency is a component of all CLIA-approved accreditation programs (see Appendix 3).

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CUMITECH 3B

The assessment of competency begins with appropriate training of personnel (see below). A wellwritten and referenced procedure manual that is constantly updated is the most important document in the clinical microbiology laboratory (60). It is the source document for training new employees and should also be used for retraining staff as technological advances occur. Competency may be assessed in a number of ways (20, 28, 34, 46, 47). These include the following:

(such as Check or Tech Samples from the ASCP). In addition, computer-based programs, supplied free by the Association for Public Health Laboratories or the Centers for Disease Control and Prevention (e.g., antimicrobial susceptibility testing), or for a fee by CLSI, can be used for educational purposes.

• • • • • •

At the core, a quality system continues to carry the messages of Shewart and Deming. Workers should be knowledgeable and trained to perform their activities, including their participation in a quality system. Quality initiatives and systems are likely to fail in the absence of active management participation. A quality system provides a process for systematic monitoring in order to correct error, to prevent error, and to create opportunities for continual improvement. All standards- and process-based systems of quality improvement clearly state that management is responsible for ensuring that a laboratory has a quality management system. The ISO standard ISO 15189:2003 (35) goes beyond recognizing that quality cannot happen “off the side of the desk.” This standard requires that there be a position known as the quality manager, whose task it is to address quality issues within the laboratory. Further, it indicates that management has the responsibility to ensure that this position is both funded and supported. For smaller facilities, this may not be the sole task of an individual; however, time needs to be allocated in a manner that allows the person to perform the tasks of a quality manager properly. By the same token, larger facilities may consider that the position of quality manager is sufficiently complex that the task should be separated into a number of positions, perhaps based upon traditional divisional lines. This could be appropriate, as long as at some regular interval all the activities are integrated so that management can perform reviews to monitor the situation and act in a manner that allows a global view of activities. Quality management provides a four-tiered structured program. The foundation of quality is the clear, unambiguous iteration of a written policy or intent. Policy statements provide the purpose and direction for all other activities. The creation and approval of policy is ultimately a management responsibility. Process is the mechanism or path by which policy is put into action. Process may involve a single procedure or a series of procedures integrated to achieve a single purpose. A procedure is a single step within the implementing process. Procedures can be described as purpose, action, and implementation. Descriptions of the procedure or recording of the procedure are

direct observation of job performance review of patient workcards participation in PT work-up of unknowns or split samples written examination supervisory review of smear results

Retraining and reassessment are mandatory if any staff member fails to meet established standards. In addition to competency in microbiology, JCAHO requires hospitals to provide annual competency evaluations of employees in fire safety, infection control, and bloodborne pathogens. Training and Continuing Education Bartlett et al. (13) suggested that a majority of employees should expend at least 5% of their time on education. With technological advances progressing by leaps and bounds, ongoing continuing education is the only way to ensure that individuals remain current in microbiology. In addition, ample training should substantially reduce laboratory errors. Staff training begins on the first day of work with the commencement of a thorough indoctrination into the laboratory’s standard operating procedure (SOP) (54). Competency assessments (described above) ensure that testing personnel understand how things should be done. Commission of errors should initiate a period of retraining that will ensure a thorough understanding of testing protocols. To maintain licensure, some states (e.g., California and Florida) require continuing education and/or recertification by a professional organization (e.g., the American Society for Clinical Pathology [ASCP], ASM, or the National Credentialing Agency). Laboratory supervisors often lament declining or nonexistent budgets for education. However, attendance at local or national workshops or meetings is only one way to ensure that testing personnel maintain up-to-date information. In-house in-service educational programs are probably the easiest way to fulfill the requirement for continuing education. In addition, many hospitals participate in audio conferences or teleconferences given by professional societies or by the National Laboratory Training Network, or they purchase self-instructional materials

GENERAL ELEMENTS OF A QUALITY SYSTEM

CUMITECH 3B

Quality Systems in the Clinical Microbiology Laboratory

examples of documentation. While standards for a quality system do not specify a single documentation format, it is a requirement that those documents, including formatted forms, be maintained as controlled documents. Visually, the quality management system is often presented as a triangle or pyramid with policy at the peak or pinnacle and documentation at the base. Clearly, a more appropriate graphic depiction is the reverse, with the base and foundation of quality management grounded in policy. It is critical that the laboratory staff be aware that the SOP that is being followed is the correct one. This can be a problem, especially when SOPs may go through a number of editions, based on changes in equipment, reagents, or circumstance. Documents that are date or version sensitive need to be maintained in a manner that distinguishes one from the other. In quality terminology, these are considered controlled documents. Controlled documents should be provided—and be recorded—with a simple unique identifier system. This commonly includes a file name or number, the most current version, and the date of the most recent creation. For example, SQF1A0603 would be the first version of document SQF1, created in June 2003, while SQF1B0604 would be the second version of the same document, adapted in June 2004. A master controlled-document log should exist to record, in order, all versions of a document so that at a glance, a person can determine which is the most current document. In some laboratories, it is commonplace to post photocopies of SOPs on the workbench. When a new version is created, it is important that all previous versions be collected and removed, in order to prevent their being incorrectly used. In some systems, a single copy of previous versions is maintained as a chronological record, so that the process of changes can be monitored. The master controlled-document log is useful and critical, but only if it is always kept current. Process improvement, or continual improvement, assumes that one knows the current status of the organization and that there is a notion that operations can be improved. It is therefore important that the laboratory have a variety of mechanisms by which the status can be monitored. External audits by licensing or accrediting bodies are blunt instruments and are rarely sufficiently timely. More appropriate processes are internal audits, combined with regular monitoring of QC and the results of external quality assessment (PT). International standards for quality management require that a regular review of all audit results be performed by management so that trends in performance can be detected and acted upon. Internal audits may be focused either on a specific bench area or on the monitoring of a predetermined

9

quality indicator. Logs of complaints, injury, accidents, or out-of-range test performances may initiate an audit process. Monitoring client satisfaction is considered a separate and special requirement by ISO standards. Continual improvement should focus not only on correcting problems (corrective actions), but also on preventing problems from developing (preventive actions). Current terminology refers to practices that do not conform to a laboratory’s expectations less as errors or defects and more as opportunities for improvement. It is important for personnel to appreciate that the opportunity for continual improvement does not mean they are not meeting expectations. With changes in circumstances and continual pressures for change from both outside and inside the facility, there are always new opportunities for quality improvement.

SPECIFIC ELEMENTS OF A QUALITY SYSTEM Management Responsibility In 1949, W. Edwards Deming wrote that without pressure from management for quality, nothing would happen (93). This concept of management responsibility for quality is established in ISO 9001 (4) and ISO 15189 (35). Effective quality management requires an annual management audit of all past activities and the determination of goals and objectives going forward. The investigation and analysis of employee suggestions and complaints, with corrective and/or definitive action, should be part of the quality management plan. In the laboratory, the designation of a quality manager is strongly recommended but in itself is insufficient without the clear and visible support of top management. Ultimately, the laboratory director is responsible for the overall operation of the laboratory, including ensuring quality and compliance with applicable regulations (90). The Laboratory Testing Circle Clinical laboratory testing has been described as a circle (50). Another approach divides the total testing process into three phases: preanalytic (test ordering, processing of the order, specimen collection and transport, and specimen accessioning), analytic (setup and performance of the test and recording of results), and postanalytic (reporting of results, interpretation of results, diagnosis, and treatment). The circle starts with the physician’s initial examination of the patient and the ordering of tests to rule out, rule in, or confirm his or her presumptive diagnosis. Tests may also be used as a means to control or evaluate the therapy given to a patient. The circle continues with the

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Anderson et al.

obtaining of the proper specimen and its transport to the laboratory. Next in the circle is the laboratory accessioning and processing of the specimen and the determination of testing modalities. This step concludes the preanalytic phase. The analytic phase of the process continues with the performance of the test, the subsequent examination of test results, and the determination of whether to subject the specimen or findings to further testing. The postanalytic phase begins with the final result being prepared, perhaps with an interpretation that is then reported back to the ordering clinician. Finally, the laboratory report is examined by the clinician, who makes an interpretation in light of other findings. New tests may be ordered to confirm the diagnosis or assist with therapy, and the circle continues. Procedure Manuals A quality system’s approach must be used in every step of the testing circle. Miller and Wentworth (49) described the laboratory procedure manual as the “most important written document in a microbiology quality control program.” In the preanalytic phase, the laboratory controls the test-ordering process through the test-ordering manual. This is the first of many procedure manuals employed in the laboratory. A hard copy or electronic version of the laboratory testordering manual should be supplied to nursing units in a hospital, to clinics that use the laboratory services, and to private practitioners who collect and send specimens from their offices. This manual also provides information for the last step of the testing cycle—the interpretation of the laboratory results. The construction of this manual, as for all others in the laboratory, should follow the guidelines laid down by the CLSI (60) and meet the requirements specified by CLIA (90). In the case of test ordering, the laboratory manual should contain information on the choice of specimen for a specific or suspected diagnosis or infection, patient preparation, the method of collection, the type of specimen collection device or container, specimen labeling, and the appropriate method for transportation, including storage or preservation. In addition, it should also contain information on how to order, what to order, and as needed, frequency of ordering. The manual should also contain information concerning the test method, expected results, normal values (if appropriate), interpretation of test results, and pertinent literature references. Most of this information can be presented in tabular or chart form (60). Last, but not least important, the manual must clearly state the criteria for specimen rejection. This manual is key to the first step in laboratory testing. While we use the axiom “garbage in, garbage out” for computer and other data processing, it accu-

CUMITECH 3B

rately portrays the need for proper specimen collection and handling for microbiology. No other section of the entire clinical laboratory has such an array and variety of specimens submitted for processing, each one requiring its own method of collection, container, and means of transportation. The details of specimen collection devices and containers, specimen collection procedures, transportation, and storage and preservation are covered in a number of excellent texts and manuals (24, 38, 50, 52, 69). The technical procedure manual for the analytic phase of testing must be available in the laboratory and must be followed by all personnel. In addition to containing the same information found in the testordering manual, the technical manual should include test principles, required reagents (including any preparation needed), test calibration, QC, procedural steps, calculations and result interpretation, clinical relevance of results (including panic or alert values), test limitations, reportable range for results, reference intervals, result recording and reporting, and a description of correction or other course of action to be taken if the calibration, controls, or test system fails (90). Some of these items may be part of the manufacturer’s instructions or operator manuals. The laboratory must supply items not provided by the manufacturer. Repeated unverifiable test results should be reported to the manufacturer immediately; continuing problems should be reported to the FDA’s MedWatch System for reporting adverse events (http://www.fda.gov/medwatch/). Therefore, the implementation of a quality system begins with the first step in the testing process. Laboratory manuals must be reviewed on a regular basis to make sure that they are up to date and contain all current procedures. Any changes to the procedures must be approved, signed, and dated by the current laboratory director prior to use. If a method in the laboratory has been changed and requires a new specimen type, volume, or mode of transport, the manual must reflect this change and the change must also be communicated to the health care provider in a timely manner. Changes in transportation regulations, particularly as they reflect the need for biosafety, are critical and must be communicated to practitioners promptly. Similarly, changes in test designation, reporting values and limits, and interpretation must be made available on a regular basis. Documentation of the procedural changes by date and how they are communicated must be kept as part of the overall quality system’s records, which must be kept for at least 2 years. Some information that is used for specimen collection, transportation, and handling can serve as quality improvement indicators (38). Some of these will be discussed below. CLSI has published an excellent guideline to assist the labora-

CUMITECH 3B

Quality Systems in the Clinical Microbiology Laboratory

tory and units that are responsible for the collection and sending of specimens to the laboratory (62). This guideline provides information that will aid in the identification, understanding, and management of sources of error and help to ensure correct results. It is targeted at those involved in the supervision of laboratory testing and addresses issues from specimen collection to the reporting of test results. Specimen Handling and Processing All of the written procedures pertaining to specimen collection, transportation, handling, and storage that are provided to the health care provider must be provided to the laboratory personnel who perform the initial processing of the specimens. As mentioned above, a key component of the laboratory manual is the specimen rejection criteria. The CAP survey manual (23) specifically requires that written criteria be provided to the health care provider and be available in the laboratory. Unacceptable samples should not be tested except under extraordinary circumstances, e.g., when the specimen cannot be recollected. If unacceptable specimens must be tested, reports should contain a disclaimer or caveat indicating that the specimen was not properly collected (or transported) and that the results may be compromised or not valid. Only persons authorized by law, which may vary from state to state, may order laboratory tests. Authorized individuals should be documented in institutional policies. Specimens submitted to the laboratory must be accompanied by a laboratory requisition (or other means if processed through a laboratory Table 4.

information system [LIS]). The requisition or order must identify the patient by name or unique identifier and include sex, age or date of birth, specimen source, the requestor, the test ordered, and the date and time (i) the specimen was collected, (ii) that it reached the laboratory, and (iii) that it was initially processed. When appropriate, the requisition should also include the type of infection and/or organism expected. The specimen itself should be labeled with at least the patient’s name or unique identifier and specimen source, when appropriate. The laboratory should maintain a specimen accession log that includes basic patient information, the accession number, and the test requested. Prior to processing, an initial examination of the specimen may be necessary to determine its suitability for culture or other processing. This would include, but not be limited to, sufficient volume, drying, appropriateness of the specimen (e.g., swabs are not suitable for anaerobic culture), or other quality indicators, such as the presence of squamous epithelial cells in sputum samples. Some of these factors can serve as excellent quality improvement indicators (Table 4) (see “Internal Quality Assessment” below). A periodic audit of the number of blood cultures collected per patient per potential septic episode can identify health care providers who are unaware that the submission of a single blood culture is inadequate for the optimal diagnosis of sepsis (8). Corrective action by direct physician contact may solve the problem, or if the problem appears to be hospital wide, a broader educational effort is required. Other blood culture

Quality improvement indicators and audits for a quality system

Phase Preanalytic

Monitor Physician ordering

Specimen collection and transport Specimen quality

Analytic

Consistency of performance of testing personnel

Postanalytic

Antimicrobial usage

a

11

Indicator or audit Urine cultures: signs and symptoms of a urinary tract infection indicating medical necessity, i.e., abnormal urinalysis (white blood cells, bacteria, albumin, hemoglobin, or nitrates), fever, flank pain, dysuria Specimen acceptability (wrong specimen container, leaking specimen container, no time of collection, acceptable transit time exceeded, labeling errors on requisition and specimen container) Sputa:
10–25 squamous cells/10 field or 10 white blood cells/10 field Wounds: presence of contaminating squamous epithelial cells; request for anaerobe culture from wound swab Urine: specimen growing
3 types of organisms Blood: insufficient volume,
2 or 3 sets per patient, or percent contaminated culturesa Any specimen (except blood):
1 specimen per day; CSFb: volume sufficient for requests; appropriate use for neurosyphilis and tuberculous meningitis diagnosis Accuracy of reading Gram stain smears: study set of 5–8 slides to be reviewed by all technologists responsible for reading and reporting Gram-stained smears (13), organism(s) present on Gram-stained smear and recovered in culture, or split-off portion of specimen (send through anonymously) and compare results between senior staff and original technologist (30); evaluate for major discrepancies, e.g., antimicrobial susceptibility changed from susceptible to resistant Continued use of antimicrobial agents despite laboratory reporting in vitro resistance (13)

Criteria established for type of organism (e.g., corynebacteria, coagulase-negative staphylococci, Bacillus spp., Micrococcus spp., viridans group streptococci, Propionibacterium acnes) and frequency per patient. b CSF, cerebrospinal fluid.

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audits may involve frequency of contamination or insufficient volumes that could identify an improperly trained phlebotomist. Audits that are difficult to quantitate should be avoided. Due to the lack of availability of media or reagents, the technical expertise of the personnel, or cost limitations, certain tests may not be performed by some laboratories. In such cases, specimens must be forwarded to a reference or other laboratory for testing. Just as it is necessary to verify and validate in-house testing, it is necessary that reference laboratories be chosen for their ability to perform the test in an accurate, reliable, and timely manner and that they be CLIA certified. Such laboratories should provide a

Table 5.

test manual listing their offerings, specimen requirements, transportation requirements, limitations of results, and turnaround times. Their policies and procedures should specify the same types of information, with respect to specimen collection and submission, as the referring laboratory. Reference laboratories should be periodically challenged with test samples to verify their claims. Guidelines for the choice and use of reference laboratories are available from CLSI (56). Media, Reagents, Stains, Analyte-Specific Reagents (ASRs), and Kits Media, commercial or user prepared, must be (i) sterile, (ii) able to support the growth of specific organ-

Recommended frequencies for performing QC on selected media, reagents, and equipment Item

Media Commercial

User prepared Transport systems Reagents Bacitracin Catalase Cefinasea Coagulase Deoxycholate ONPGb Optochin Oxidase PYR disksb Spot indole Staphylococcal latex Streptococcal latex XV disks and stripsc DNA probes Mycobacteriology Mycologyd Antisera Antimicrobial susceptibility testing Aerobic bacteria

Frequency

Comment or reference(s)

Accept NCCLS M22-A3.Test each lot and shipment of nonexempt media when opened or prepared. Test each batch when prepared. Accept NCCLS M40-A. By batch, lot, and shipment when opened prepared. By batch, lot, and shipment when opened prepared. By batch, lot, and shipment when opened prepared. By batch, lot, and shipment when opened prepared. By batch, lot, and shipment when opened prepared. By batch, lot, and shipment when opened prepared. By batch, lot, and shipment when opened prepared. By batch, lot, and shipment when opened prepared. By batch, lot, and shipment when opened prepared. By batch, lot, and shipment when opened prepared. By batch, lot, and shipment when opened prepared. By batch, lot, and shipment when opened prepared. By batch, lot, and shipment when opened prepared. By batch, lot, and shipment when opened prepared and each day of use. By batch, lot, and shipment when opened prepared and each day of use. By batch, lot, and shipment when opened prepared. By batch, lot, and shipment when opened prepared and once every 6 months.

Accept NCCLS M2-A8 and M7-A6.

55, 90

38, 55, 90 69

or

Test for positive and negative reactivities.

or

Test for positive and negative reactivities.

or

Test for positive and negative reactivities.

or

Test for positive and negative reactivities.

or

Test for positive and negative reactivities.

or

Test for positive and negative reactivities.

or

Test for positive and negative reactivities.

or

Test for positive and negative reactivities.

or

Test for positive and negative reactivities.

or

Test for positive and negative reactivities.

or

Test for positive and negative reactivities.

or

Test for positive and negative reactivities.

or

Test for positive and negative reactivities.

or

Test for positive and negative reactivities.

or or

Test for positive and negative reactivities with an acid-fast organism. Test for positive and negative reactivities.

or

Test for positive and negative reactivities.

67, 68, 90

CUMITECH 3B

Quality Systems in the Clinical Microbiology Laboratory

isms and/or inhibit the growth of others, and (iii) give an appropriate biochemical response. Refer to Table 5 for specific items and recommended frequencies of QC testing. Commercially Prepared Media Commercially prepared culture media should be logged in upon receipt in the laboratory. The names of the manufacturer and distributor, lot number, expiration date, and date of receipt should be recorded, and the product information document should be retained. Some manufacturers provide these items in ways that are convenient for the laboratory to retain. The CLSI has published a document, M22-A3 (55),

Table 5.

that lists the commercial media that are exempt from testing for sterility or performance characteristics as long as the vendor has provided documentation that QC has been performed according to CLSI standards. These standards specify test organisms that the manufacturer must use, incubation conditions, and acceptable results. The user must visually examine each lot number and shipment of media for breakage, contamination, appearance, or evidence of the effect of temperature or mishandling and must document these observations. The user must test each lot number and shipment of a wide variety of nonexempt media for performance characteristics (90). These include media not

Continued Item

Antimicrobial susceptibility testing Anaerobic bacteria Fungi Stains Acid-fast stain Gram stain Special stains (e.g., spore, capsule, flagella) Fluorescent stains Fluorochrome stain (AFB)e Lactophenol cotton bluef Parasitology stains Commercial identification kitsg Equipment Temperature Carbon dioxide pH meter Autoclave Thermometer Ocular micrometer Biological safety cabinets Microliter pipettes a

Frequency

Comment or reference(s)

Accept NCCLS M11-A6. Accept NCCLS M44-P, M38-A, and M27-A2.

63, 90 64, 72, 90

By batch, lot, and shipment when opened or prepared and each day of use. By batch, lot, and shipment when opened or prepared and weekly. By batch, lot, and shipment when opened or prepared and each day of use.

Test for positive and negative reactivities.

By batch, lot, and shipment when opened or prepared and each time of use. By batch, lot, and shipment when opened or prepared and each time of use. By batch, lot, and shipment when opened or prepared. By batch, lot, and shipment when opened or prepared and monthly. By batch, lot, and shipment when opened or prepared. Follow manufacturer’s schedule for preventive maintenance. Daily. Weekly. Each day of use. Weekly with bacterial spores; each cycle checked with heat-sensitive tape or recording thermometer. Before placing in service. Calibrate before placing in service and each time that the eyepieces or objectives are changed. Certify annually.

Test for positive and negative reactivities. Test for positive and negative reactivities.

Test for positive and negative reactivities. Test for positive and negative reactivities.

Use a fecal control. Test for positive and negative reactivities.

Use 3 reference buffers.

Use NISTh-certified device or one guaranteed by manufacturer to meet NIST standards. New York State requires biannual calibration.

Before first use and at specified intervals.

Beta-lactamase tests (other than cefinase) must be checked each day of use with a positive and negative control. ONPG, o-nitrophenyl
-D-galactopyranoside; PYR, pyrrolidony l--naphthylamide. c A negative reactivity control is not required for X and V disks or strips. d A negative reactivity control is not required for a germ tube test. e AFB, acid-fast bacilli. f Test positive reactivity with a filamentous mold. g Systems using two or more substrates or two or more reagents or a combination. h NIST, National Institute of Standards and Technology. b

13

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specifically addressed in M22-A3, as well as lots of Mueller-Hinton agar, Campylobacter agar, some selective media for Neisseria spp., and media in kits consisting of two or more different substrates used primarily for microbial identification. It is strongly recommended that QC testing be performed on exempt media used for the recovery of fastidious microorganisms (e.g., Neisseria gonorrhoeae, Haemophilus influenzae, Campylobacter spp., Legionella spp., and Burkholderia cepacia). In addition, media having relatively high failure rates must be tested using in-houseestablished QC methods. Critical reactions using applied reagents (e.g., the CAMP test) not tested by the manufacturer must also be checked in-house. For virology, manufacturers must provide evidence that continuous cell lines are checked for mycoplasmas and that animal sera used for cell growth media have been checked for toxicity. Media used for the isolation of parasites, viruses, mycoplasmas, and Chlamydia must be tested by the user. When cell culture is used for viral isolation, the laboratory must simultaneously incubate a cell substrate control or uninoculated cells to serve as a negative control. The manufacturer must be notified of any observed deficiency, and there must be documentation of such notification and any corrective action. The protocol used for checking commercially prepared media is considered part of the laboratory procedure manual. Media and cell lines must be stored according to the manufacturer’s recommendations. User-Prepared Media Certain culture procedures may require the preparation of media in-house, most often to ensure freshness or the rapid availability of the media. At the time of preparation or concurrently with its use, each batch of medium must be tested with selected organisms to confirm the required growth characteristics, selectivity, enrichment, and biochemical response (49, 90). Stock reference organisms (see below) should be maintained in the laboratory for this purpose. There must be a means of labeling and recording the identity of the media, batch or lot numbers, storage requirements, preparation date, date placed in use, expiration date, and identity of the preparer. Containers of dehydrated media and reagents used to prepare in-house products should be labeled with the date of receipt and the date first opened. Since it may be onerous to label numerous individual tubes or plates of prepared media, tubes with tightened caps and plating media may be stored in airtight plastic bags or racks that are labeled as described above. However, all elements of appropriate labeling must be recorded in a logbook, and the individual items must be identified so as to be traceable to the appropriate data in the log. At a minimum, it is recom-

CUMITECH 3B

mended that the identity of the medium be labeled on each individual plate or tube. For laboratories preparing large quantities of media, it will be easier to purchase a labeling system to label each tube or plate. Reagents and Stains All reagents (including water, dry media, stains, and disks containing reagents or antimicrobial agents) must be labeled with the contents, concentration, storage requirements, date prepared or reconstituted, and expiration date or expected shelf life. Labeling reagents with the date received is not required but is useful for inventory management. Reagents must be stored according to the manufacturer’s recommendations. Reference organisms should be used to check all stains, reagents, and disks; at least one organism producing a positive reaction and one producing a negative reaction must be tested with each batch, lot number, and shipment. Materials with substandard reactivity or deteriorated materials must not be used. Antisera are to be tested with known positive and negative organisms. Table 5 summarizes the required frequencies of QC testing of laboratory reagents. ASRs ASRs are not approved by the FDA for testing specimens obtained from humans. Therefore, the laboratory must establish performance specifications for test systems that use ASRs (26). As required for other methods developed in-house, the data must demonstrate that the accuracy, precision, analytical sensitivity and specificity, reportable range, and reference interval (normal values) for the procedure are adequate as determined by the laboratory director or technical supervisor (90). Kits Commercially obtained kits that include a variety of media or reagents provide a challenge for QC. Kits may include media, biochemicals and other reagents, antimicrobial agents, or any combination of these materials. Some may be used manually or with some form of instrumentation. It is necessary that the individual medium or reagent displays the appropriate color, growth, and positive or negative reactions, and the final result or answer provided by the kit must be accurate as well. Manufacturer-recommended QC strains of organisms should be tested with each lot number and shipment of kits, but other supplemental QC organisms may be required to monitor the performance characteristics of each reagent or substrate in the test system. Currently, CLIA defines an identification system as a system using two or more substrates or two or more reagents, or a combination, and each substrate or reagent must be tested for positive and negative reactivity (90). Likewise, the CAP

CUMITECH 3B

Quality Systems in the Clinical Microbiology Laboratory

requires that positive and negative controls be tested and that results be recorded for all identification systems (23). In order to change or make exceptions to the QC requirements in the CLIA regulations, scientifically valid data supporting the proposed change or exception must be submitted to CMS for consideration and must be applicable to all commercial identification systems. Like any other material, there must be a record of receipt, date put into use, and expiration date documented for each lot number and shipment of kits (90). QC Organisms Laboratories are required to maintain a stock of organisms that can be used for validating the reactions received on media or with reagents, stains, and other biochemicals or determining the accuracy of antimicrobial testing systems. In most cases, manufacturers of the materials will provide the necessary information for obtaining the organisms, which should be registered with the American Type Culture Collection (ATCC) (P.O. Box 1549, Manassas, VA 20108; http://www.atcc.org). In addition to the ATCC, other commercial sources may supply the organisms in lyophilized or other forms for ease of handling. Prior to use, it is best that the test or control organism be passaged at least two times on an appropriate growth medium. However, it is also important that the organism not be subcultured excessively during use so that the stability of the strain is not compromised. Several CLSI documents provide complete details on the preparation of inocula and maintenance of reference cultures (67, 68, 73). Instruments and Equipment Performing maintenance and function checks of equipment is an extremely important function in the clinical laboratory and is required under CLIA (90). Although scheduled preventive maintenance (PM) is costly in terms of downtime and personnel time, the cost is insignificant compared to that of emergency repair, material, and additional personnel time. PM may be defined as a program of scheduled inspection resulting in minor adjustment or repair to delay or prevent major repair or emergency or premature replacement of instruments and equipment and to maintain optimum operating characteristics (49, 90). PM requires preplanning by scheduling inspection and maintenance functions. In addition, it must be a realistic, organized, and documented program. Function checks are performed to evaluate critical operating characteristics (e.g., rotator speed, stray light, or background counts) of all equipment and instruments, including those items (e.g., autoclaves, centrifuges, and incubators) that are peripheral to test-

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ing patients’ specimens. Manufacturers often define the function checks and frequency of performance. In the absence of a manufacturer’s recommendation, the laboratory must develop a function check protocol. In general, function checks are performed daily prior to testing patient samples to ensure that the instrument is operating correctly and is properly calibrated. Daily QC, calibration, calibration verification, and validation activities may serve as additional function checks. Calibration is the process that is applied to the quantitative adjustment of equipment to ensure its accurate operation throughout its measuring limits; calibration verification refers to testing material of known concentration to substantiate the calibration throughout the reportable range, and validation applies to those steps taken to confirm and record the proper operation of equipment at one point in the range in which the test is performed (61, 90). The frequency with which validation or calibration is performed depends on the kind of equipment, its frequency of use, and the manufacturer’s recommendations. At a minimum, calibration verification must be performed every 6 months or after major maintenance or malfunction of the instrument (90). While the manufacturer may suggest minimal maintenance procedures, the function checks must be documented each day of use or at least as often as recommended by the manufacturer. Key personnel must regularly review the results of equipment validation and calibration, and out-of-limits findings must be documented with remedial action. Miller and Wentworth (49) provide an excellent resource for conducting a PM program for all types of instruments and equipment: glassware, thermometers, pipettes, incubators, microscopes, water baths, centrifuges, biosafety cabinets, sterilizers, and automated equipment. Test and Culture Examination and Organism Identification Clinical microbiology has increasingly incorporated the use of manual, semiautomated, and automated instrumentation, leading one to believe that the science has become very objective. Despite this, the interpretation of culture results and their reporting are still subjective. The assessment of each culture for different colony types and the decision to perform individual biochemical or reagent tests or to identify the isolate with an instrument requires a very subjective analysis on the part of the technologist. Whether the organism is identified with an instrument, a kit, or an in-house system, each step of the process must be monitored by some form of QC. Even the procedures for the abbreviated identification of bacteria and yeast must be checked (59). As discussed above, QC is to be performed on media, reagents, kits, instruments,

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and systems used for the identification of organisms. While not recorded with the individual specimen workups, records of such QC activities, whenever performed, must be kept and should be available throughout the laboratory, because each technologist should be aware of the performance of the media, reagents, and equipment. An excellent internal quality assurance indicator is a comparison of the results obtained from culture to those available from the examination of the direct Gram stain. This comparison is available only for specimens on which a direct Gram stain is made, either by request or as part of the culture setup (e.g., wounds and cultures of tissue). If organisms are present in the stained smear but are not found on culture, further steps may be necessary in the evaluation of the culture (e.g., anaerobic or acid-fast culture or longer incubation), or examination of other laboratory procedures or reagents may be required (e.g., reexamination of the direct Gram stain, checking the Gram stain reagents for contamination, or checking the quality of culture media). The value of sputum and endotracheal aspirates in the diagnosis of respiratory tract infections is controversial, in part because they are commonly contaminated by bacteria colonizing the oropharnyx. In general, the routine workup of these specimens should be directed by the examination of the Gram stain and the quality of the specimen and limited to two or three potential pathogens recovered in culture (86). Urine culture results should be reviewed periodically. The isolation of two or more types of organisms from voided urine samples usually indicates contamination upon collection or improper handling of specimens (21). It is difficult to establish standards for the percentage of urine cultures with mixed flora that constitute acceptable practice. The repeated isolation of mixed flora may indicate mixed infection or colonization and should not necessarily be considered a sign of unsatisfactory collection procedure. The proportion of patients with indwelling urinary catheters will affect the percentage of urine cultures showing mixed flora. If 5% or more of the urine specimens are truly unsatisfactory, then corrective action is probably needed. Training in the collection and prompt delivery of specimens to the laboratory or the use of a preservative (e.g., boric acid) may alleviate the problem. Comparison of audit data before and after the remedial action is always necessary to document the effectiveness of a corrective measure. As discussed above, frequent review of blood culture results may show excessive or unusual patterns of contaminating organisms, information which may document improper venipuncture procedures (8). Results of anaerobic cultures should be checked against aerobic cultures of the same specimen (79).

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Because different technologists may examine the two cultures on different days, it is not unusual to recover different organisms in the cultures. Similar comparisons can be made between fungal and bacterial or mycobacterial and bacterial cultures. The results of infrequently performed tests or requests for the isolation and identification of unusual organisms should be reviewed frequently by key laboratory personnel who have expertise in that particular area of microbiology. The documentation of such differences in results or unusual findings will lead to improvement in the overall technical expertise of personnel through education. Molecular technologies, such as nucleic acid amplification tests (NAATs), require special attention. By design, they have numerous, unique, built-in QC checks (53, 70). However, there are several important considerations for ensuring the quality of NAATs. First, if the NAATs are not contained in a closed system, they must be conducted using a unidirectional laboratory workflow, including separate areas for specimen preparation, amplification, product detection, and, as applicable, reagent preparation. In addition, at least once each day of testing, a positive and a negative control must be tested, and if reaction inhibition is a significant source of false-negative results, an internal control that is capable of detecting the inhibition must be included (90). Technologies such as fluorescent in situ hybridization, pulsed-field gel electrophoresis, and genotyping by nucleotide sequencing all require new approaches to assessing the quality of the test and its result. Another challenge is the continual discovery of new pathogens, all of which place a burden on the already busy laboratory but nevertheless require some form of quality assurance for organism isolation or identification. Quality assurance audits should be chosen carefully to address the most urgent, frequent, or interesting problems. It is important not to undertake more than one or two studies at a time. One welldone quality assurance indicator evaluation is worth more than many done poorly. Periodic surveys of other health care personnel who use the laboratory can also help assess how the laboratory is perceived by its users. Nurses, and physicians especially, should be queried regarding the laboratory response to telephone inquiries (courtesy and delay) and turnaround time between specimen collection and the appearance of results on the patient’s chart. Records of such surveys and any corrective action should be maintained. Antimicrobial Susceptibility Testing The results of antimicrobial susceptibility tests may be markedly influenced by a number of technical variables. These include inoculum density, stability of the drug, incubation time, temperature and atmos-

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phere, medium composition, ionic content, and pH. Manually read test results are subject to operator ability and interpretation; instrumented test results are subject to software and other mechanical variables of the instrument. These test variables can be controlled by adhering to the CLSI standard antimicrobial susceptibility testing procedures (67, 68, 73) or, in the case of tests performed by an instrument, the manufacturer’s instructions. The CLSI standards are revised on an annual basis; therefore, the most recent publications should be available to the laboratory. When out-of-control results occur with a particular antimicrobial agent, the results of testing clinical isolates against that drug should not be reported. The test should be repeated, and if necessary, an investigation of factors influencing the erroneous result should be undertaken (e.g., evaluating a fresh ATCC QC strain). For any system, manual (e.g., disk diffusion), semiautomated, or automated, used for determining the susceptibility of organisms to selected antimicrobial agents, QC testing must be performed whenever new lots of agent or other material are used. In general, for disk diffusion testing, the potency of the antimicrobial disks must be checked prior to the disk being placed in service and at least weekly thereafter (68, 90). Note that control stains must be tested daily until the accuracy and precision have been validated by 20 or 30 consecutive days of testing. To convert from daily testing to weekly QC testing, no more than 1 out of 20 or 3 out of 30 zone diameters for each antimicrobial agent-organism combination may be outside the acceptable zone diameter. Reference ATCC strains having known susceptibility patterns should be used. Zone sizes must be recorded and limits must be observed, and if the drug is out of range, it must be retested on five consecutive days. If results are still outside the control limits, accuracy and precision must be reestablished by 20 or 30 consecutive days of additional testing. A Levy-Jennings chart is a convenient and acceptable way to document disk-testing results (61). Broth macro- or microdilution or agar dilution tests should have control organisms with known susceptibility patterns run with each new lot and at least weekly thereafter (67, 73, 90). As with disk diffusion tests, the laboratory must document its proficiency in performing dilution tests by satisfactory testing for 20 or 30 consecutive days in order to reduce the frequency of QC testing from daily to weekly. Criteria have been defined by CLSI for endpoint determination and interpretation (67, 73). When semiautomated or automated systems are used for susceptibility testing, the manufacturer’s recommendations also must be followed, including frequency of QC testing, choice of QC organisms,

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expected results, and corrective action. In most cases, the organisms used are the same ones recommended by CLSI for either dilution or diffusion testing (67, 68, 73, 90). Recording, Interpretation, Reporting, and Record Retention CLIA regulations require that the laboratory maintain an information or record system (manual or computer) that includes (i) positive identification of the specimen, (ii) date and time of specimen receipt, (iii) condition and disposition of unacceptable specimens, (iv) records and dates of all testing and personnel who performed the test(s), and (v) retention of all instrument printouts (90). Part of the laboratory’s record system often includes work cards for recording tests performed on a patient’s specimen. This type of record should not be written in pencil, and the use of whiteout is not acceptable for making corrections on the work card. In addition, the recording of data on work cards must be consistent throughout the laboratory for all personnel—consistency that can be achieved only by the continual review and evaluation of individual culture work cards and reports. Therefore, it is necessary that work cards, whether a hard copy or within an LIS, be consistent in design and be completed in a consistent manner. This will facilitate the review of the work card and its comparison to the result at the time of report release or later review. The consistency of this documentation is also necessary during the processing of a culture if the culture is incubated further, additional tests are performed, and the ongoing process is followed up by a different technologist. The work card for each specimen or culture is used to record notes made by the technologist and supervisory personnel and interaction between the clinician and laboratory personnel. A properly completed work card can be used to reconstruct the process and assess the accuracy of the final report. The report that is recorded on the work card may be conveyed to the ordering physician by hard copy or through the LIS. The test report must contain (i) the name of the patient and identification number (or a unique identifier), (ii) name and address of the laboratory performing the test, (iii) testing date, (iv) test performed, (v) specimen source when appropriate, (vi) test results with units of measurement or interpretation or both, (vii) information on the disposition of unacceptable specimens, and (viii) reference intervals or “normal values.” In addition, the laboratory must, upon request, make available the test method and performance specifications, as well as a list of test interferences (90). The test result can be conveyed only to an authorized person, and all critical values must be conveyed immediately. The laboratory

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must also have a policy for verification readback of critical values that are communicated verbally or by telephone. If testing is delayed, the person who ordered the test should be notified. Critical values should be established by laboratory policy. This test report becomes an official permanent (and legal) part of the patient’s hospital record. There are several types of reports: telephone, preliminary, final, corrected, and additional or supplementary. The telephone report, which may also be conveyed in person, is used to report information that is critical to the patient’s care. This report may include information from the examination of microscopic smears, antigen tests, or growth from normally sterile body fluids (blood or cerebrospinal fluid) or information on agents of highly infectious diseases (tuberculosis or anthrax). Even though given orally, the action must be recorded on the work card and optionally included as part of the final report. The preliminary report is designed to report the status of a test within 24 to 48 h after receipt of the specimen and may contain only minimal information. It is important that the medical staff understand that preliminary reports are subject to change. The final report conveys the results after all the tests have been completed. The supervisor or designee should review the results prior to release and before they are placed in the patient’s record as a method to detect and correct significant errors that may affect patient care. Corrected reports are used only to notify the ordering physician that the original (final) report was erroneous. Corrected reports should be preceded by personal contact with the physician to explain the nature of the error. The corrected report must be identified as such, and the original/ final report should not be deleted or removed from the patient’s record. The date of the correction and the initials of the person making the correction must be recorded (90). An additional or supplementary report is used when additional information is discovered concerning the patient specimen and/or culture. It does not negate or correct the original final report; it provides only supplementary information. Such a report may be issued upon the late growth of an organism in a blood culture. Corrected reports and supplemental reports must be part of the quality improvement system. Errors or missed information must be followed up, and corrective action must be documented. An integral part of many laboratories is the LIS. Many LISs have built-in checks and balances for identifying corrected or additional reports and errors concerning specimen and patient identification. The LIS also provides a system for maintaining records, collecting data, and collating data from reports (71). The LIS can provide summaries of these records by hard copy or for viewing electronically. These inter-

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nal programs provide a valuable resource for assessing the continuing quality output of the laboratory. A flexible LIS has the ability to accept textual comments that provide an opportunity to augment, clarify and interpret test results or recommend further testing. While not always captured as a part of the final report, they nevertheless provide another step in the total quality systems management. Record retention requirements specified by CLIA and used by accreditation organizations (e.g., CAP, COLA, and JCAHO) and states generally stipulate that laboratories must retain the following records for 2 years (7): • records of specimens received and test requests, including the patient identification, name of submitter, date of receipt, type of test performed and test result (including work cards and instrument printouts), and test report • test procedures (including dates of initial use and discontinuance) • records of test system performance specifications verified or established by the laboratory • records of QC and quality assurance procedures and reports • PT results • records of inspections, validations, and instrument maintenance In addition, the Occupational Safety and Health Administration requires retention of records relating to safety and bloodborne pathogen training, occupational exposure to hazardous chemicals or biological agents, and record keeping and reporting of occupational injuries and illnesses. Generally, records pertaining to training are held for 3 years, those on occupational injuries and illnesses for 5 years following the end of the year to which they relate, and those on exposure to hazardous chemicals, microbial pathogens, and hepatitis B virus vaccination for 30 years following the end of employment.

EXTERNAL QUALITY ASSESSMENT Participation in external quality assessment programs (e.g., inspections and proficiency-testing programs) ideally provides a comparison or benchmark against other laboratories, is required by federal regulation in the United States, and, most importantly, can identify significant errors in the testing process. Although these programs are general in nature, when performed well, they offer an outside evaluation of the laboratory that is invaluable. In any case, a process should be in place to handle external assessments that includes scheduling, preassessment paperwork, receiving assessors, conducting assessments, closing

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summaries, follow-up response, and corrective action (66). To facilitate the process, employees should be informed of the inspection dates and what to expect. Key individuals should be assigned to a surveyor so that they are familiar with the material and can be a resource. Inspections and Accreditation The passage of the CLIA regulations in the United States established minimum standards for laboratory personnel and laboratory testing of specimens obtained from humans and mandated federal certification and inspections. The focus of laboratory inspections is to ensure compliance with CLIA standards and to provide suggestions to correct any deficiencies. The CAP attempts to improve the quality of laboratory testing through peer-reviewed education and inspections, JCAHO provides consultation on performance improvement, and CMS uses an educational approach to ensure compliance. COLA generally inspects physician office laboratories and smaller community hospitals, using a friendly peer review process. Regardless of the organization performing the inspection, the process should assess all three phases (i.e., preanalytic, analytic, and postanalytic) of laboratory testing. This includes items such as test orders, specimen integrity during transport, QC monitors, appropriate storage conditions for reagents and supplies, procedure manuals, testing or examination procedures, and reporting of test results. Overall, the inspection process should provide an opportunity to share ideas with peers for improvement of laboratory services. PT PT programs (see Appendix 5) supply samples of unknown analytes to participating laboratories to assess the ability of laboratory personnel to achieve the correct response (58). All PT samples need to be integrated within the routine laboratory workload and analyzed by personnel who routinely test patient samples. There must not be any communication with other laboratories or test system manufacturers concerning PT results prior to reporting the results to the PT program. The premise is that an acceptable performance on a PT specimen suggests that analysis of patients’ specimens is also acceptable. This premise may not be correct, considering the special handling and attention the PT samples often receive (77). Under CLIA, participation in a CMS-approved program is mandated for certain tests, and each laboratory must participate in PT according to its microbiology subspecialty (e.g., virology) and type of services (e.g., direct antigen testing or organism identification). PT samples are sent three times per year, and each micro-

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biology laboratory must test at least five samples per testing event for each subspecialty in which they are CLIA certified. Laboratories that achieve less than 80% correct responses on two of three testing events will face potentially negative consequences. Under the current CLIA regulations, PT samples are graded when the percentage for consensus agreement among laboratories is at least 80% (90). In addition, laboratories are required to review and evaluate their performance on all PT samples, graded or ungraded. A potential benefit of PT is the ability to compare or benchmark against participating laboratories. PT is an assessment of the preanalytic and analytic phases of laboratory testing and takes into account variables such as matrix effects, clerical errors, and sample preparation. It is essential that PT samples be tested in the same manner as a patient specimen if the exercise is to have any value. However, PT results should not be the sole indicator of the quality of laboratory testing. Investigation of unacceptable PT results should be documented and should lead to corrective actions to prevent similar problems. All aspects of the testing process should be evaluated, such as clerical errors, past QC records, test performance, and whether the identified problem affected past patient testing (66). Technical problems include improper reconstitution of the sample; inappropriate media, stains, and workup; or misinterpretation of the result. Methodological and technical problems are usually related to instruments, reagents, media, and incubation conditions. Alternatives to External PT External PT programs do not provide test samples for all analytes tested in the clinical laboratory, especially in microbiology. Tests for which PT may not be readily available include the following (65): • newly developed tests • uncommonly performed or esoteric tests (e.g., tests for Histoplasma urinary antigen or antibodies to Bartonella spp.) • tests for which PT cannot be developed (e.g., fecal leukocytes) • fastidious microorganisms (e.g., Bordetella pertussis) • susceptibility tests for anaerobes and fungi • hazardous microorganisms (e.g., dimorphic fungi or Salmonella enterica serovar Typhi) However, laboratories should attempt to develop alternative assessment procedures (AAP) for those tests for which PT is not available, not only because it is required by CLIA but, more importantly, because AAP can provide information on the performance of the particular test method. In-house AAPs provide

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more timely data than external PT programs and in many cases evaluate the steps in the preanalytic phase of laboratory testing. The AAP should be documented in the procedure manual, results of the testing should be retained, and corrective action should be taken when unacceptable results occur. CLIA requires that AAP be performed at least twice per year. After the laboratory has identified the tests without commercially available PT, an AAP must be chosen that measures the performance of the test. Possible approaches to AAPs include the following. • Split samples: send an aliquot to another laboratory or test the sample by another method or operator. • Analyze a stored sample periodically over time. • Test commercial control material or other reference material. • Use surrogate microorganisms for fastidious or hazardous organisms. • Develop specimen exchange programs with other laboratories. • Perform clinical correlation studies when an infectious process can be diagnosed or is strongly suggested by the patient’s symptoms. Note that ethics and/or institutional review board committees may require that patient consent be obtained before the patient’s sample is used for any purpose other than that for which it was ordered, including quality assurance. Other Quality Assessment Programs Most PT programs focus on the analytic phase of the laboratory’s testing process. In the United States, two CAP programs, Q-Probes and Q-Tracks, emphasize the pre- and postanalytic phases of laboratory testing. The Q-Probes program provides quality assurance studies with peer comparison, while the Q-Tracks program monitors changes in quality indicators over time. Both programs provide the necessary data collection methods, worksheets, and input forms, which are analyzed, and the data are compared (benchmarked) to those of other participants. In Canada, the Clinical Microbiology Proficiency Testing program has developed beyond the traditional analyticphase model and addresses challenges within both pre- and postanalytic phases (77; http://www.cmpt.ca).

INTERNAL QUALITY ASSESSMENT Quality Indicators JCAHO introduced the requirement for monitoring of indicators in 1985 (40). An indicator was defined as an aspect of a process that may have a significant effect on patient outcome (42). This requirement led

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to the development by CAP of the Q-Probe program described above. Microbiologists began studying quality indicators even before it was an accreditation requirement (Table 4) (see “Specific Elements of a Quality System” above for additional indicators). The first indicator studied was specimen quality (9, 10, 11, 48). Sputum evaluation by direct microscopy was one of the first items examined, as was contamination of blood cultures (83, 94). Attention continued to focus on specimens in subsequent years (12, 29, 45, 51, 91). A common indicator has been underutilization of blood cultures, especially the percentage of single draws and the volume of blood collected per bottle. However, attention has also shifted to other indicators, including length of patient stay in the hospital (14), patient morbidity, increased patient longevity or quality of life, lowered cost of therapy, the timely reporting of stat results (33), and the proportion of treatment regimens adjusted after microbiology results are known (17, 25). Error Detection There are numerous indications that the errors that occur in the medical laboratory are a risk to patient safety. Each laboratory must establish a mechanism for detection of errors and must show positive trends demonstrating improvements in the percentage of errors detected (3). For example, an occasional review of the patient’s chart or LIS report may reveal errors (e.g., organism identification or antimicrobial susceptibility test reporting) detected only by direct review of the patient’s record. An error is considered to result when SOPs are not followed. These types of incidents must be documented by the laboratory, and errors can be categorized either by analyzing these reports or by monitoring corrected reports. Bartlett et al. (13) grouped errors either by (i) the source of the error, i.e., physician, nurse, unit clerk, microbiology testing personnel, or outside (reference) laboratory personnel, or (ii) type of occurrence. Errors can be divided into those that occur in the preanalytic, analytic, and postanalytic phases of laboratory testing. Interestingly, most errors seem to occur in the pre- and postanalytic phases (43). Examples of errors in the preanalytic phase are incorrect test selection, improper sample collection and transport, and accessioning errors, while errors in the postanalytic phase include delayed test reporting, incorrect recording or transcription of results, and misinterpretation of results. Verification and Validation Under CLIA, test system (or method) verification or the establishment of performance specifications is

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required for any test system introduced into a laboratory after 23 April 2003 (26, 90). If the laboratory introduces an unmodified commercial test system, the test must first be verified (i.e., evaluated) for accuracy, precision, reportable range, and appropriateness of the reference range for each laboratory’s particular patient population. Verification demonstrates that the laboratory can reproduce a manufacturer’s claims for accuracy, precision, and reportable range and/or that the new test method is at least as good as the test in current use or an accepted reference method. If the laboratory introduces a modified commercial test system, a test that has been developed inhouse (not subject to FDA clearance or approval), or one for which performance specifications have not been provided by the manufacturer, before reporting patient results, the laboratory must establish performance specifications for accuracy, precision, analytical sensitivity and specificity, and reportable range and an appropriate reference range for each laboratory patient population. Ongoing validation of an existing, verified test documents that the test continues to perform satisfactorily and may be confirmed by reviewing QC data, performance of the test on external or internal PT samples, and/or correlation with clinical patient data. Audits Audits are surveys that are undertaken to analyze quality indicators and patient outcomes. Quality assessment audits should be chosen carefully to address the most urgent or interesting problems in a particular institution. Audits should address all phases of laboratory testing, not just the analytic phase. Examples of possible audits in each phase are shown in Table 4. Internal audits are an essential part of all quality systems. The laboratory can develop a program of regular bench-by-bench or section-by-section audits to monitor activity and compliance with the laboratory’s quality plan. Performed on a regular basis, each individual audit consumes a minimum of time, and yet if performed on a quarterly basis, audits provide considerable information for improvement (76). Internal audits provide an opportunity for the entire laboratory to become engaged in the quality process. An example of an internal audit form is shown in Appendix 6. Benchmarking The term “benchmarking” applies to a comparison of laboratory performance to that of other laboratories of the same size and type, i.e., for-profit hospitals versus other for-profit hospitals or universityaffiliated hospitals versus other university-affiliated

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hospitals. Indicator data are collected for comparative purposes to enable benchmarking (78). There are quality benchmarks, as well as financial benchmarks. Sometimes, health care consultants confuse the two, as when they make personnel decisions based on productivity without comparing apples to apples. An example of this is benchmarking the number of fulltime employees required to perform 6,000 screens for group A streptococci to the number doing 6,000 wound cultures from patients with diabetic foot ulcers. Quality benchmarks are projects of CAP’s QProbes and Q-Tracks programs described above. Specific information is requested, and laboratories then compare themselves to their peer group. Wells and Winn (95, 96), provide a more detailed discussion of benchmarks and benchmarking.

SUMMARY A quality system is an approach to continuously analyze and improve the processes and services within an organization. This concept has been applied to the management of medical laboratories within the United States and around the world, and some countries mandate that laboratories have a comprehensive quality system in operation. The document ISO 15189 provides the guidelines for a quality management system in the laboratory for most countries in the world. In the United States, CLIA serves a similar function. CLIA defines minimum standards for laboratory quality based on the category (i.e., waived or moderate or high complexity) of testing performed by the laboratory and contains standards for the entire testing process, personnel, PT, quality assessments, and document control. In general, a quality system is a mix of regulatory standards (usually minimum quality standards) and voluntary standards (usually the best practices). This combination of standards provides the basis for managing the quality of the procedures and processes that are integral to performing tests on human specimens and to continuously evaluating selected quality indicators as a means to improve performance and patient outcome. The quality system is applied to the entire testing process, including the preanalytic, analytic, and postanalytic phases, to detect, correct, and prevent errors and to create opportunities to improve the processes and services. APPENDIX 1 WEBSITES FOR CLIA AND QUALITY SYSTEM INFORMATION 1. http://www.phppo.cdc.gov/clia/regs/toc.asp 2. http://www.cms.hhs.gov/clia/dirclcon.asp

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3. http://www.cms.hhs.gov/clia/cliaapp.asp 4. http://www.cms.hhs.gov/clia/progdesc.asp 5. http://www.cms.hhs.gov/clia/appendc.asp (surveyor guidelines) 6. http://www.cms.hhs.gov/clia/ssa-map.asp 7. Centers for Disease Control and Prevention: http:// www.phppo.cdc.gov/clia/default.asp 8. CMS: http://www.cms.hhs.gov/clia/default.asp 9. FDA: http://www.fda.gov/cdrh/clia/index.html (listing of waived, moderate-complexity, and high-complexity tests) 10. http://www.fda.gov/medwatch/

APPENDIX 2 DEFINITIONS AND ABBREVIATIONS See references 41, 66, 80, 84, 85, 95, and 96 for more information. Accreditation Process by which an organization or program demonstrates that it has met specific requirements or standards based on a review by an independent examiner(s). Accrediting organizations Private, nonprofit organizations approved by CMS to conduct laboratory inspections to determine whether a laboratory meets quality standards and is in compliance with the CLIA regulations. Accuracy Agreement between the best estimate of a quantity and its true value. Analyte Substance or constituent to be measured. Analyte-specific reagents (ASRs) Antibodies, proteins, ligands, nucleic acid sequences, and any chemical substances that are used in diagnostic tests for identification and quantification of another specific substance in a biological specimen and that are purchased from the manufacturer under this label. The FDA describes an ASR as an “active ingredient of an in-house test.” Analytic processes Activities and steps related to performing laboratory examinations. Note: ISO uses the term examination to describe these processes, and define it as a “set of operations having the object of determining the value of a property.” ASCP

American Society for Clinical Pathology.

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Calibration verification Assaying of materials of known concentration in the same manner as patient specimens to substantiate the instruments’ or test systems’ calibration throughout the reportable range for patient test results. Centers for Disease Control and Prevention (CDC) Federal agency responsible for providing scientific and technical consultation with respect to CLIA. Centers for Medicare and Medicaid Services (CMS) Federal agency (previously Health Care Financing Administration) responsible for the administration of CLIA and oversight of clinical laboratory testing and certification. Certification A voluntary or mandatory program usually administered by a governmental agency or professional association recognizing that the individual or organization has met certain requirements. Clinical Laboratory Improvement Amendments of 1988 (CLIA) Governing regulations that apply to all laboratories in the United States that perform testing of human specimens for the diagnosis, prevention, or treatment of disease or assessment of human health. Clinical and Laboratory Standards Institute (CLSI) A voluntary global organization that develops consensus guidelines and standards for clinical and laboratory practice. Formerly named NCCLS until 1 January 2005. College of American Pathologists (CAP) A professional association of pathologists that provides laboratory proficiency testing and accreditation services. COLA An organization (formerly Commission on Office Laboratory Accreditation) that provides voluntary education, consultation, and laboratory accreditation services primarily for physician office and other small laboratories. Food and Drug Administration (FDA) Federal agency responsible for the oversight of commercial tests and for their approval, licensure, and CLIA categorization for use in clinical laboratories. HHS U.S. Department of Health and Human Services. ISO International Organization for Standardization. Joint Commission on Accreditation of Healthcare Organizations (JCAHO) An organization that accredits health care facilities and components of their services, such as laboratory testing.

ASM American Society for Microbiology.

Laboratory information system (LIS) The computer system for laboratory services.

Benchmark A standard against which performance is measured. The standard represents the best possible performance. Benchmarks include various internal, external, industry-wide, and nonindustry performance measures.

Licensure Status granted to an organization or individual who has met minimum requirements set by a regulatory agency; permits licensees to practice their profession in a given location.

Benchmarking A management tool that compares a laboratory’s performance against the performance of its peers. The goal is to identify the “best performance” and employ these processes to improve performance.

NCA

Calibration Process of testing and adjusting (by comparison to a standard) an instrument or equipment that ensures the instrument or equipment operates accurately throughout the measuring range.

Nonwaived Replaces the terms moderate- and high-complexity testing when referring to the CLIA requirements that pertain to both levels of testing.

National Credentialing Agency.

NCCLS See Clinical and Laboratory Standards Institute (CLSI).

NRM

National Registry of Microbiologists.

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Quality Systems in the Clinical Microbiology Laboratory

Path of workflow Sequential processes in preanalytic, analytic, and postanalytic clinical laboratory activities that transform a physician’s order into laboratory information. Point-of-care (POC) testing Testing performed at the patient’s bedside or other site of care outside of a laboratory facility. Postanalytic processes All processes following laboratory examination, including systematic review, formatting and interpretation, authorization of release, reporting of results, storage and retention of specimens and data, and assessment of the effects of results on patient outcomes. Note: ISO 15189 uses the term postanalytical phase or postexamination phase to describe the same concept. Preanalytic processes Steps starting in chronological order from the clinician’s request, including the laboratory examination requisition, preparation of the patient, collection of the primary sample, and transportation to and within the laboratory, and ending when the analytical examination procedure starts. Note: ISO 15189 uses the term preanalytical phase or preexamination phase to describe the same concept. Procedure A specified method to carry out an activity that may involve a single step or series of steps to achieve a purpose. Process A set of interrelated or interacting activities that transform inputs into outputs. Proficiency testing An external quality assessment process in which specimens are sent to each member of a group of laboratories for measurement or detection of specific analytes. The results from each laboratory are compared to those of the other members of the group to assess the individual laboratory’s performance. Provider-performed microscopy procedures (PPMP) A subcategory of moderate-complexity testing under CLIA that permits physicians, midlevel practitioners, and dentists to conduct specific microscopic examinations during a patient visit as part of the patient’s evaluation. A PPMP certificate allows a provider to perform PPMP and waived tests. Quality assessment or quality assurance A planned and systematic process for evaluating and monitoring the quality and appropriateness of patient care by focusing on finding problems. Quality control A process for monitoring assay performance to detect deviations from expected outcomes. Quality improvement A system for identifying processes that can be used to improve performance and customer satisfaction in all aspects of testing, including the preanalytic, analytic, and postanalytic phases. Quality system Refers to all of a laboratory’s policies, procedures, and resources needed to achieve quality testing. Quality system essentials Coordinated management activities to direct and control an organization with regard to quality.

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Six Sigma An approach to improving quality that involves measuring defects or adverse events against a common measure of variation. Total quality management A system of integrating multiple programs to provide the processes by which quality improvement can be implemented and maintained. Validation Documentation that a verified test continues to perform satisfactorily according to the manufacturer’s claims for its intended use over a period of time. Verification One-time demonstration and documentation that the performance characteristics of a test are comparable to those established by the manufacturer before the test is used for patient testing. The performance characteristics include sensitivity, specificity, and, where appropriate, the predictive values, precision, accuracy, reportable range of results, and reference intervals (normal values) of the test. Waived testing Under CLIA, laboratory tests that have been cleared by the FDA for home use or that are simple tests with low risk of an erroneous result. Laboratories that perform only waived tests may operate under a Certificate of Waiver.

APPENDIX 3 CLIA-APPROVED ACCREDITATION ORGANIZATIONS Information in this appendix is current as of February 2005. American Association of Blood Banks 8101 Glenbrook Rd. Bethesda, MD 20814-2749 (301) 907-6977 http://www.aabb.org American Osteopathic Association 142 East Ontario St. Chicago, IL 60611 (312) 202-8070 http://do-online.osteotech.org/index.cfm?PageID acc_hfmain Offers an approved program for microbiology laboratories American Society of Histocompatibility and Immunogenetics 1700 Commerce Pkwy. Mt. Laurel, NJ 08054 (856) 642-4415 http://www.ashi-hla.org COLA (national health care accreditation organization) 9881 Broken Land Pkwy., Suite 200 Columbia, MD 21046-1195 (410) 381-6581 http://www.cola.org/prodsandservs/labaccred.asp?cart_id Offers an approved program for microbiology laboratories

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Anderson et al.

College of American Pathologists 325 Waukegan Rd. Northfield, IL 60093-2750 (800) 323-4040 http://www.cap.org/apps/cap.portal Offers an approved program for microbiology laboratories

CUMITECH 3B

Typically, POLs that accept referred testing are considered independent laboratories. States regulating POLs also regulate hospital and independent laboratories. Several states require laboratory personnel to be licensed and to meet requirements that are more stringent than CLIA. This table does not address personnel regulation issues. The table is reproduced with permission from COLA.

Joint Commission on Accreditation of Healthcare Organizations One Renaissance Blvd. Oakbrook Terrace, IL 60181 (630) 792-5000 http://www.jcaho.org/htba/laboratoryservices/index.htm Offers an approved program for microbiology laboratories

APPENDIX 5 EXAMPLES OF PT PROGRAMS FOR MICROBIOLOGY LABORATORIES

APPENDIX 4 STATES THAT REGULATE OR LICENSE CLINICAL LABORATORIES

Accutest, Inc. (CLIA approved) P.O. Box 999 Westford, MA 01886 (800) 665-2575

State

Laboratories

Alabama . . . . . Arizona . . . . . . Arkansas . . . . . California . . . . . Connecticut . . . Florida . . . . . . . Georgia . . . . . . Idaho . . . . . . . . Illinois . . . . . . . Kentucky . . . . . Maine . . . . . . . Maryland . . . . . Massachusetts

. . . . . . . . . . . . .

. . . . . . . . . . . . .

Nebraska . . . . . . . Nevada . . . . . . . . New Hampshire . New Jersey . . . . . New York . . . . . . .

Oregon . . . . . . . .

Pennsylvania Rhode Island Tennessee . . Washington .

. . . .

. . . .

. . . .

. . . .

.Hospital and independent laboratories .Law repealed .Hospital and independent laboratories .All laboratories—not fully implemented .All laboratories .All laboratories .Hospital and independent laboratories .Licensure law is superseded by CLIA .Law repealed .Independent laboratories .Hospital and independent laboratories .All laboratories . Hospital and independent laboratories and limited regulation of physician office laboratories (POLs) (≥3 physicians) . Implementation of state law delayed indefinitely .All laboratories . Hospital and independent laboratories . Hospital and independent laboratories and limited regulation of POLs (≥5 physicians) .CLIA exemption for hospital and independent laboratories; POLs comply with CLIA only .All laboratories; regulations in force, but most laboratories are not issued state licenses . All laboratories . Hospital and independent laboratories . Hospital and independent laboratories . All laboratories; CLIA exempt

The information in the table above was updated in April 2002. Because of the fluid nature of legislative and regulatory matters in the states, the information contained in this table should be confirmed before making any decisions concerning individual laboratory licensure or registration.

American Academy of Family Physicians (CLIA approved) 11400 Tomahawk Creek Pkwy. Leawood, KS 66211-2672 (800) 274-7911 American Association of Bioanalysts (CLIA approved) 205 West Levee St. Brownsville, TX 78520-5596 (800) 234-5315 American Proficiency Institute (API) (CLIA approved) 1159 Business Park Dr. Traverse City, MI 49686 (800) 333-0958 Clinical Microbiology Proficiency Testing Program (available in Canada) Department of Pathology and Laboratory Medicine University of British Columbia Vancouver, British Columbia V5Z 1M9 Canada (866) 579-CMPT (Canada and United States) (604) 875-4685 College of American Pathologists (surveys and EXCEL) (CLIA approved) 325 Waukegan Rd. Northfield, IL 60093-2750 (800) 323-4040 Laboratoire de Santé Publique du Québec (available in Canada) 20 045 Chemin Sainte-Marie Sainte-Anne-de-Bellevue, Québec H9X 3R5 Canada (514) 457-2070 (Attention Jean Joly) Medical Laboratory Evaluation (CLIA approved) 2011 Pennsylvania Ave. NW, Suite 800 Washington, DC 20006-1834 (800) 338-2746

CUMITECH 3B

Quality Systems in the Clinical Microbiology Laboratory

New Jersey Department of Health and Senior Services (CLIA approved) Proficiency Testing Program for Clinical Laboratories Clinical Laboratory Improvement Service P.O. Box 361 Trenton, NJ 08625-0361 (609) 292-5605, option 3 New York State Department of Health (CLIA approved) The Governor Nelson A. Rockefeller State Plaza P.O. Box 509 Albany, NY 12201-0509 (518) 474-8739

Accessioning verification

25

Examine all samples received Yes No for C. difficile samples TODAY

Are all C. difficile samples received in the correct container as identified in the manual as being required and appropriate for the sample? When samples were received in incorrect containers, were they rejected for C. difficile analysis? Are all C. difficile samples traceable to the patient (are they labeled by either name or number)? Additional comments on the initial accessioning of C. difficile samples:

Puerto Rico Department of Health (CLIA approved) Laboratory Program P.O. Box 70184 San Juan, PR 00936-8184 (809) 274-7735 Quality Management Program—Laboratory Services (available in Canada) 1510 250 Bloor St. East Toronto, Ontario M4W 1E6 Canada (877) 323-9540 (Attention Harold Richardson) Wisconsin Proficiency Testing Program (CLIA approved) State Laboratory of Hygiene 465 Henry Mall Madison, WI 53706-1578 (800) 462-5261

APPENDIX 6 EXAMPLE OF A SELF-EVALUATION SURVEY Clostridium difficile Manuals

Examine all manuals relevant Yes No to C. difficile

Is there a written manual (or clearly identifiable sections in a number of manuals) that is readily available that describes the procedures required to fulfill the work requirements for processing? C. difficile samples Is the manual (or the sections of manuals pertaining to C. difficile samples) up to date and signed off by the appropriate person? If there is more than one copy of the manual available, are all copies identical in content and sign-off?

Bench environment

Yes No

Is the available work space set up to work on C. difficile samples sufficient to allow safe work habits? Is the available work space set up to allow work to be completed efficiently? Is the equipment available at the work space in proper working condition? Is the available work space sufficient for the volume of work required? Is the available work space sufficient to prevent risks of in-laboratory contamination of C. difficile samples? Are work notes or derivatives of the manual available in the work space? Are work notes or derivatives identical to the most current manual? Additional comments on workbench space provided for processing and handling C. difficile samples:

If sections pertaining to C. difficile samples are located in different books or locations, is there a documented pathway to give guidance to find relevant sections as required? Additional comments on manuals and documentation available for working on C. difficile samples:

(Continued)

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Technologist competencies

CUMITECH 3B

With respect to the technologists working TODAY on C. difficile samples Yes No

Is the technologist at the work station trained in all procedures required for proper processing of C. difficile samples?

Internal quality control and external quality assessment

Yes No

Are all organisms and reagents required for internal quality control readily available? Is there a written instruction on which internal quality control tests must be performed on a regular basis?

Is there a file which describes courses or training taken by the technologist in the last 2 years that has been deemed essential to ensure proper processing of C. difficile samples?

Is there documented evidence that all internal quality control tests that were required for TODAY were performed TODAY?

Additional comments on documentation of technologist competencies to perform analyses of C. difficile samples:

Are external quality assessment (proficiency testing) samples being performed at the bench TODAY? If external proficiency testing samples are being processed at this workbench, are they being processed in the same manner as routine samples? Is there evidence of external quality control specimens specific to the C. difficile samples having been processed in the last 12 months? Additional comments on documentation of internal quality control and external quality assessment for analyses of C. difficile samples:

Process verification

Consider all samples processed on the day of inspection

Yes No

Were the procedures used to analyze the C. difficile sample today consistent with the current procedure manual?

Results reporting

Were results from the C. difficile samples reviewed by one or more person(s) to affirm their accuracy?

Was the released result consistent with the workup as described?

Was the documentation of procedures used consistent with current requirements as described in the procedure manual?

Was the results report consistent with the format and content described in the most current procedure manual?

Additional comments on documentation of procedures undertaken to verify analyses of C. difficile samples:

If final results differed from preliminary results, were the preliminary results amended in a traceable fashion?

Consider all samples reported Yes No within the last 48 hours

Additional comments on results reported for C. difficile samples:

CUMITECH 3B

Quality Systems in the Clinical Microbiology Laboratory

Results reporting Examine all samples reported Yes No (turn around) within the last 48 hours Did any C. difficile samples tested and reported in the last 2 days require more than 4 working days to complete? Did any samples require more than 7 working days to complete? If the answer to either of the above is YES, record the circumstances associated with the prolonged-time sample in the comment section. Additional comments on turnaround time of results reported for C. difficile samples.

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6. Anonymous. 2004. DMAIC methodology. http//www. isixsigma.com/me/dmaic/. 7. Baer, D. 2004. Saving laboratory records: what, how, how long? MLO Med. Lab. Obs. 36:10–16. 8. Baron, E. J., M. P. Weinstein, W. M. Dunne, Jr., P. Yagupsky, D. F. Welch, and D. M. Wilson. 2005. Cumitech 1C, Blood Cultures IV. Coordinating ed., E. J. Baron. ASM Press, Washington, D.C. 9. Bartlett, R. C. 1982. Making optimum use of the microbiology laboratory. I. Use of the laboratory. JAMA 247:857–859. 10. Bartlett, R. C. 1982. Making optimum use of the microbiology laboratory. II. Urine, respiratory, wound, and cervicovaginal exudates. JAMA 247:1336–1338. 11. Bartlett, R. C. 1982. Making optimum use of the microbiology laboratory. III. Aids of antimicrobial therapy. JAMA 247:1868–1871. 12. Bartlett, R. C. 1990. Trends in quality management. Arch. Pathol. Lab. Med. 114:1126–1130. 13. Bartlett, R. C., M. Mazens-Sullivan, J. Z. Tetreault, S. Lobel, and J. Nivard. 1994. Evolving approaches to management of quality in clinical microbiology. Clin. Microbiol. Rev. 7:55–88.

Conclusions:

Opportunities for improvement in processing C. difficile samples:

14. Beekmann, S. E., D. J. Diekema, K. C. Chapin, and G. V. Doern. 2003. Effects of rapid detection of bloodstream infections on length of hospitalization and hospital charges. J. Clin. Microbiol. 41:3119–3125. 15. Borbeau, P. P. 2003. Role of the microbiology laboratory in diagnosis and management of pharyngitis. J. Clin. Microbiol. 41:3467–3472.

Reviewer

Laboratory Representative

Reproduced from reference 76.

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Quality Systems in the Clinical Microbiology Laboratory

52. Murray, P. R., E. J. Baron, J. H. Jorgensen, M. A. Pfaller, and R. H. Yolken (ed.). 2003. Manual of Clinical Microbiology, 8th ed., p 33–104. ASM Press, Washington, D.C. 53. NCCLS. 1995. Molecular Diagnostic Methods for Infectious Diseases. Approved guideline MM3-A. NCCLS, Wayne, Pa. 54. NCCLS. 1995. Training Verification for Laboratory Personnel. Approved guideline GP21-A. NCCLS, Wayne, Pa. 55. NCCLS. 2004. Quality Control for Commercially Prepared Microbiological Culture Media. Approved standard M22-A3, 3rd ed. NCCLS, Wayne, Pa.

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56. NCCLS. 1998. Selecting and Evaluating a Referral Laboratory. Approved guideline GP9-A. NCCLS, Wayne, Pa.

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