The Clinical Laboratory Is an Integral Component to Health Care Delivery : An Expanded Representation of the Total Testing Process.

OBJECTIVES: Developing an expanded representation of the total testing process that includes contemporary elements of laboratory practice can be useful to understanding and optimizing testing workflows across clinical laboratory and patient care settings. METHODS: Published literature and meeting reports were used by the coauthors to inform the development of the expanded representation of the total testing process and relevant examples describing its uses. RESULTS: A visual representation of the total testing process was developed and contextualized to patient care scenarios using a number of examples covering the detection of blood culture contamination, use of next-generation sequencing, and pharmacogenetic testing. CONCLUSIONS: The expanded representation of the total testing process can serve as a model and framework to document and improve the use of clinical testing within the broader context of health care delivery. This representation recognizes increased engagement among clinical laboratory professionals with patients and other health care providers as essential to making informed decisions. The increasing use of data is highlighted as important to ensuring quality, appropriate test utilization, and sustaining an efficient workflow across clinical laboratory and patient care settings. Maintaining a properly resourced and competent workforce is also featured as an essential component to the testing process.

Managing biological variation data: modern approaches for study design and clinical application.

For more than one half-century, variability observed in clinical test result measurements has been ascribed to three major independent factors: (i) pre-analytical variation, occurring at sample collection and processing steps; (ii) analytical variation of the test method for which measurements are taken, and; (iii) biological variation (BV). Appreciation of this last source of variability is the major goal of this review article. Several recent advances have been made to generate, collate, and utilize BV data of biomarker tests within the clinical laboratory setting. Consideration of both prospective and retrospective study designs will be addressed. The prospective/direct study design will be described in accordance with recent recommendations discussed in the framework of a newly-developed system of checklist items. Potential value of retrospective/indirect study design, modeled on data mining from cohort studies or pathology laboratory information systems (LIS), offers an alternative approach to obtain BV estimates for clinical biomarkers. Moreover, updates to BV databases have made these data more current and widely accessible. Principal aims of this review are to provide the clinical laboratory scientist with a historical framework of BV concepts, to highlight useful applications of BV data within the clinical laboratory environment, and to discuss key terms and concepts related to statistical treatment of BV data.

Bringing the clinical laboratory into the strategy to advance diagnostic excellence.

OBJECTIVES: Clinical laboratory testing provides essential data for making medical diagnoses. Generating accurate and timely test results clearly communicated to the treating clinician, and ultimately the patient, is a critical component that supports diagnostic excellence. On the other hand, failure to achieve this can lead to diagnostic errors that manifest in missed, delayed and wrong diagnoses. CONTENT: Innovations that support diagnostic excellence address: 1) test utilization, 2) leveraging clinical and laboratory data, 3) promoting the use of credible information resources, 4) enhancing communication among laboratory professionals, health care providers and the patient, and 5) advancing the use of diagnostic management teams. Integrating evidence-based laboratory and patient-care quality management approaches may provide a strategy to support diagnostic excellence. Professional societies, government agencies, and healthcare systems are actively engaged in efforts to advance diagnostic excellence. Leveraging clinical laboratory capabilities within a healthcare system can measurably improve the diagnostic process and reduce diagnostic errors. SUMMARY: An expanded quality management approach that builds on existing processes and measures can promote diagnostic excellence and provide a pathway to transition innovative concepts to practice. OUTLOOK: There are increasing opportunities for clinical laboratory professionals and organizations to be part of a strategy to improve diagnoses.

Evaluating the Adoption of Laboratory Practice Guidelines.

CONTEXT.­: To date, the College of American Pathologists (CAP) has developed 17 laboratory practice guidelines (LPGs) including updates. In 2013, the CAP was awarded a 5-year cooperative agreement grant from the United States Centers for Disease Control and Prevention to increase the effectiveness of LPGs. OBJECTIVE.­: To assess the awareness and adoption of 2 CAP LPGs: immunohistochemical (IHC) assay validation and initial workup of acute leukemia. DESIGN.­: Baseline surveys for each LPG were conducted in 2010 and 2015, respectively. To measure the adoption of guideline recommendations and inform future updates, a follow-up study consisting of surveys, telephone interviews, and focus group sessions was conducted in laboratories that indicated they perform IHC testing. A follow-up study for the acute leukemia LPG is planned. RESULTS.­: For the IHC Validation LPG, a total of 1624 survey responses, 40 telephone interviews, and discussions with 5 focus group participants were analyzed. The response rate for the aforementioned 3 modalities was 46%, 13%, and 3%, respectively. All modalities indicated most respondents were aware of the LPG and had adopted most or all of its recommendations. Respondents expressed needs for continued communication, increased specificity, and more prescriptive recommendations when the guideline is updated. CONCLUSIONS.­: While data-driven development of evidence-based LPGs requires significant resources, active data collection to identify gaps and assess adoption contributes to improved laboratory testing practices in support of patient care. The CAP identified sustainable modalities to track metrics and developed multiple tools that should improve guideline development, adoption, and implementation. Of these modalities, written or electronic surveys were the most logistically feasible and had the highest response rate.

Impact of testosterone assay standardization efforts assessed via accuracy-based proficiency testing.

BACKGROUND: We reported observations on analytical performance in testosterone measurements of various methods/assays from the study carried out using accuracy-based proficiency testing (PT) during 2012-2013. In 2016, we re-evaluated analytical performance of testosterone assays using accuracy-based PT to assess effectiveness of CDC efforts toward standardization. METHODS: Five single-donor human serum samples from female and male adult donors were analyzed for testosterone by New York State Department of Health-certified clinical laboratories using 16 immunoassays and LC-MS/MS methods. Target values were determined using the CDC reference measurement procedure. RESULTS: Testosterone targets for the 5 samples were 43.5, 160, 294, 457, and 534 ng/dL. The biases of individual result of the 65 participant laboratories against the target for each sample were calculated. Of participants, 87.7% had ≥4 of the 5 results within the minimum allowable total error limits (± 25.1%), a 14.7% increase from the previous study. The improved PT scores were attributed to better analytical accuracy and precision, and laboratories' selection of more accurate assays/methods. CONCLUSIONS: Improved analytical accuracy and precision for testosterone assays were demonstrated over a 3.5-year period after the first CDC-directed accuracy-based proficiency testing. Additional effort is needed to improve accuracy/precision of measurements, especially at low concentrations.

Analytic Validation of Immunohistochemistry Assays: New Benchmark Data From a Survey of 1085 Laboratories.

CONTEXT: - A cooperative agreement between the College of American Pathologists (CAP) and the United States Centers for Disease Control and Prevention was undertaken to measure laboratories' awareness and implementation of an evidence-based laboratory practice guideline (LPG) on immunohistochemical (IHC) validation practices published in 2014. OBJECTIVE: - To establish new benchmark data on IHC laboratory practices. DESIGN: - A 2015 survey on IHC assay validation practices was sent to laboratories subscribed to specific CAP proficiency testing programs and to additional nonsubscribing laboratories that perform IHC testing. Specific questions were designed to capture laboratory practices not addressed in a 2010 survey. RESULTS: - The analysis was based on responses from 1085 laboratories that perform IHC staining. Ninety-six percent (809 of 844) always documented validation of IHC assays. Sixty percent (648 of 1078) had separate procedures for predictive and nonpredictive markers, 42.7% (220 of 515) had procedures for laboratory-developed tests, 50% (349 of 697) had procedures for testing cytologic specimens, and 46.2% (363 of 785) had procedures for testing decalcified specimens. Minimum case numbers were specified by 85.9% (720 of 838) of laboratories for nonpredictive markers and 76% (584 of 768) for predictive markers. Median concordance requirements were 95% for both types. For initial validation, 75.4% (538 of 714) of laboratories adopted the 20-case minimum for nonpredictive markers and 45.9% (266 of 579) adopted the 40-case minimum for predictive markers as outlined in the 2014 LPG. The most common method for validation was correlation with morphology and expected results. Laboratories also reported which assay changes necessitated revalidation and their minimum case requirements. CONCLUSIONS: - Benchmark data on current IHC validation practices and procedures may help laboratories understand the issues and influence further refinement of LPG recommendations.

Analytic Validation of Immunohistochemical Assays: A Comparison of Laboratory Practices Before and After Introduction of an Evidence-Based Guideline.

CONTEXT: - Laboratories must demonstrate analytic validity before any test can be used clinically, but studies have shown inconsistent practices in immunohistochemical assay validation. OBJECTIVE: - To assess changes in immunohistochemistry analytic validation practices after publication of an evidence-based laboratory practice guideline. DESIGN: - A survey on current immunohistochemistry assay validation practices and on the awareness and adoption of a recently published guideline was sent to subscribers enrolled in one of 3 relevant College of American Pathologists proficiency testing programs and to additional nonsubscribing laboratories that perform immunohistochemical testing. The results were compared with an earlier survey of validation practices. RESULTS: - Analysis was based on responses from 1085 laboratories that perform immunohistochemical staining. Of 1057 responses, 65.4% (691) were aware of the guideline recommendations before this survey was sent and 79.9% (550 of 688) of those have already adopted some or all of the recommendations. Compared with the 2010 survey, a significant number of laboratories now have written validation procedures for both predictive and nonpredictive marker assays and specifications for the minimum numbers of cases needed for validation. There was also significant improvement in compliance with validation requirements, with 99% (100 of 102) having validated their most recently introduced predictive marker assay, compared with 74.9% (326 of 435) in 2010. The difficulty in finding validation cases for rare antigens and resource limitations were cited as the biggest challenges in implementing the guideline. CONCLUSIONS: - Dissemination of the 2014 evidence-based guideline validation practices had a positive impact on laboratory performance; some or all of the recommendations have been adopted by nearly 80% of respondents.

Practices and Perceived Value of Proficiency Testing in Clinical Laboratories.

BACKGROUND: Proficiency testing (PT) can have regulatory and nonregulatory uses, providing an effective tool for quality improvement. Clinical laboratories were surveyed to determine how they perceive PT and how they use PT results and materials to improve laboratory testing quality. METHODS: All laboratories certified to perform nonwaived testing under the CLIA regulations expected to perform required PT were invited to participate in the survey. We examined respondents' use of PT from 5 laboratory types: hospital, independent, public health, physician office, and "all other." Respondents' awareness of resources about PT was also examined. Several questions allowed responses on a categorical scale. RESULTS: Varying proportions of the respondents (n = 769) used PT to identify problems in the preanalytic (48%), analytic (86%), and postanalytic (76%) phases of testing. Responses also showed that PT was important for demonstrating personnel competency (93%), inappropriate specimen handling (80%), incorrect result interpretation (84%), and other uses. Respodents purchased PT even when not required to do so (77%). Based on all responses, most considered PT worth the cost (65%). CONCLUSIONS: Laboratories, regardless of type, have found ways of using leftover PT samples and the information from PT event summaries to help improve laboratory quality. Our findings suggest many laboratories are not taking full advantage of PT to improve testing quality. Additionally, the study suggests a need to improve awareness of resources about PT.

Trends in laboratory test volumes for Medicare Part B reimbursements, 2000-2010.

CONTEXT: Changes in reimbursements for clinical laboratory testing may help us assess the effect of various variables, such as testing recommendations, market forces, changes in testing technology, and changes in clinical or laboratory practices, and provide information that can influence health care and public health policy decisions. To date, however, there has been no report, to our knowledge, of longitudinal trends in national laboratory test use. OBJECTIVE: To evaluate Medicare Part B-reimbursed volumes of selected laboratory tests per 10,000 enrollees from 2000 through 2010. DESIGN: Laboratory test reimbursement volumes per 10,000 enrollees in Medicare Part B were obtained from the Centers for Medicare & Medicaid Services (Baltimore, Maryland). The ratio of the most recent (2010) reimbursed test volume per 10,000 Medicare enrollees, divided by the oldest data (usually 2000) during this decade, called the volume ratio, was used to measure trends in test reimbursement. Laboratory tests with a reimbursement claim frequency of at least 10 per 10,000 Medicare enrollees in 2010 were selected, provided there was more than a 50% change in test reimbursement volume during the 2000-2010 decade. We combined the reimbursed test volumes for the few tests that were listed under more than one code in the Current Procedural Terminology (American Medical Association, Chicago, Illinois). A 2-sided Poisson regression, adjusted for potential overdispersion, was used to determine P values for the trend; trends were considered significant at P < .05. RESULTS: Tests with the greatest decrease in reimbursement volumes were electrolytes, digoxin, carbamazepine, phenytoin, and lithium, with volume ratios ranging from 0.27 to 0.64 (P < .001). Tests with the greatest increase in reimbursement volumes were meprobamate, opiates, methadone, phencyclidine, amphetamines, cocaine, and vitamin D, with volume ratios ranging from 83 to 1510 (P < .001). CONCLUSIONS: Although reimbursement volumes increased for most of the selected tests, other tests exhibited statistically significant downward trends in annual reimbursement volumes. The observed changes in reimbursement volumes may be explained by disease prevalence and severity, patterns of drug use, clinical or laboratory practices, and testing recommendations and guidelines, among others. These data may be useful to policy makers, health systems researchers, laboratory directors, and industry scientists to understand, address, and anticipate trends in laboratory testing in the Medicare population.

Performance of tuberculosis drug susceptibility testing in U.S. laboratories from 1994 to 2008.

We present a statistical summary of results from the Model Performance Evaluation Program (MPEP) for Mycobacterium tuberculosis Drug Susceptibility Testing, 1994 to 2008, implemented by the U.S. Centers for Disease Control and Prevention (CDC). During that period, a total of 57,733 test results for culture isolates were reported by 216 participating laboratories for the first-line antituberculosis drugs used in the United States-isoniazid (INH), rifampin (RMP), ethambutol (EMB), and pyrazinamide (PZA). Using Clinical Laboratory and Standards Institute (CLSI)-recommended concentrations for one or more of three methods, agar proportion (AP), BACTEC460 (Bactec), and MGIT-960 (MGIT), yielded overall agreement of 97.0% for first-line drugs. For susceptible strains, agreement was 98.4%; for resistant strains, agreement was 91.0%, with significantly lower accuracy (chi-square test, P < 0.0001). For resistant strains, overall agreement by methods was 91.3% for AP, 93.0% for Bactec, and 82.6% for MGIT and by drugs was 92.2% for INH, 91.5% for RMP, 79.0% for EMB, and 97.5% for PZA. For some strains, performance by method varied significantly. Use of duplicate strains in the same shipment and repeat strains over time revealed consistent performance even for strains with higher levels of interlaboratory discordance. No overall differences in performance between laboratories were observed based on volume of testing or type of facility (e.g., health department, hospital, independent). By all methods, decreased performance was observed for strains with low-level INH resistance, RMP resistance, and EMB-resistant strains. These results demonstrate a high level of performance in detection of drug-resistant M. tuberculosis in U.S. laboratories.

Differential West Nile fever ascertainment in the United States: a multilevel analysis.

We evaluated the completeness of West Nile fever (WNF) surveillance within the U.S. public health system. We surveyed laboratory and surveillance programs on policies, practices, and capacities for testing, confirmation, and reporting (collectively called ascertainment) from 2003 through 2005. We calculated syndrome ascertainment ratios by dividing WNF counts by neuroinvasive disease counts; separately, we performed multilevel modeling. Jurisdictions were more likely to ascertain at least one WNF cases per West Nile neuroinvasive disease case when ≤ 1 testing restrictions existed (odds ratio [OR] = 7.7, 95% confidence interval [CI] = 1.3-46.4), when conducting ≥ 4 activities to enhance reporting (OR = 9.3, 95% CI = 1.6-54.8), and when ≥ 5.0 staff per million residents were dedicated to arboviral surveillance (OR = 6.4, 95% CI = 1.0-40.3). Ascertainment of WNF was less likely among Blacks (OR = 0.56, 95% CI = 0.31-0.99) and Hispanics (OR = 0.69, 95% CI = 0.48-0.98) than among Whites. Ascertainment was more complete when testing and reporting were enhanced, but differentially incomplete for minorities.

The State Public Health Laboratory System.

This article describes the development since 2000 of the State Public Health Laboratory System in the United States. These state systems collectively are related to several other recent public health laboratory (PHL) initiatives. The first is the Core Functions and Capabilities of State Public Health Laboratories, a white paper that defined the basic responsibilities of the state PHL. Another is the Centers for Disease Control and Prevention National Laboratory System (NLS) initiative, the goal of which is to promote public-private collaboration to assure quality laboratory services and public health surveillance. To enhance the realization of the NLS, the Association of Public Health Laboratories (APHL) launched in 2004 a State Public Health Laboratory System Improvement Program. In the same year, APHL developed a Comprehensive Laboratory Services Survey, a tool to measure improvement through the decade to assure that essential PHL services are provided.

Origins and development of the National Laboratory System for public health testing.

Although not recognized as such, a National Laboratory System (NLS) has existed since the inception of public health laboratory (PHL) testing more than a century ago. The NLS has always relied upon the participation of clinical laboratories, both to report test results that represent public health threats and to submit specimens and isolates to PHLs for additional or confirmatory testing. Historically, a number of factors have hindered the strengthening of the relationships between clinical laboratories and PHLs, but the reality of bioterrorism and subsequent focus on strengthening public-private relationships has stimulated the development of a more robust NLS. Since 2002, there has been substantial strengthening of the NLS through the sharing of lessons learned from several demonstration projects. There is a growing emphasis on defining critical elements of the NLS, including the State Public Health Laboratory System (SPH Laboratory System) and the functions of the Laboratory Program Advisor, a position that every state should have at the center of its laboratory system's capacity-building. Additional strengthening of the NLS is occurring through (1) national biennial measurement of state PHLs' abilities to meet the Core Functions and Capabilities of State PHLs, (2) the new Laboratory System Improvement Program (L-SIP) for the SPH Laboratory System, and (3) sharing ideas to integrate and improve the SPH Laboratory System (e.g., using the L-SIP Online Resource Center). Public health emergencies, such as the recent H1N1 epidemic, illustrate and reinforce the need for a strong NLS within which federal, public health, and clinical (i.e., hospital and private reference) laboratories function in close collaboration.

Laboratory services in support of public health: a status report.

OBJECTIVES: To assess Healthy People 2010 Objective 23-13 and its related sub-objectives measuring comprehensive laboratory services in support of essential public health programs, the Association of Public Health Laboratories (APHL) collaborated with the Centers for Disease Control and Prevention (CDC) to create and administer a survey of state public health laboratories (PHLs). METHODS: A committee of APHL, with representation from CDC, constructed the survey based on the 11 Core Functions of State Public Health Laboratories (hereafter, Core Functions)--the premise being that the extent to which they fulfilled these Core Functions would represent their level of providing or assuring comprehensive laboratory services in support of public health. The survey was distributed biennially to all state health agencies from 2004 to 2008, and respondents were given two months to complete it. RESULTS: The response rate for all surveys was > or = 90.2%. State PHLs were more likely to meet the sub-objectives relating to traditional functions (e.g., disease surveillance and reference testing) than other areas (e.g., food safety and environmental testing). Emergency preparedness fell in between. Overall, but most notably in the areas of food safety and training and education, there was improvement from 2006 to 2008, with the percentage of respondents who met more than half of the sub-objectives increasing from 58.7% in 2006 to 61.2% in 2008. CONCLUSIONS: The comprehensive laboratory services survey has been a valuable tool in measuring the laboratory infrastructure that underpins public health in the U.S. It will be necessary to continue monitoring laboratory infrastructure in this way to determine where the gaps in services exist and how they can best be addressed.

Systems approach to improving antimicrobial susceptibility testing in clinical laboratories in the United States.

Laboratory practice in the preanalytical phase of antimicrobial susceptibility testing (AST) was evaluated in 102 hospital, reference, physician office-clinic, and public health laboratories in Washington state. Surveys were sent to evaluate (i) use of NCCLS/CLSI (formerly NCCLS) AST performance standards, (ii) technical competence in AST case studies, challenging knowledge of contemporary testing issues, and (iii) choice of antimicrobial agents to test for Streptococcus pneumoniae. Numerous deficiencies were identified in the survey: (i) initially only 40% of the laboratories surveyed used current NCCLS/CLSI AST performance standards, (ii) the rate of accurate responses for three different case studies ranged from 29% to 69%, and (iii) variation was noted in the choice of antimicrobials tested against invasive isolates of S. pneumoniae. These deficiencies could affect therapy and detection of antimicrobial resistance. Several educational programs were implemented to improve AST policies and practices, and a follow-up survey indicated that four intervention strategies were most effective: (i) regional technical workshops, (ii) National Laboratory Training Network teleconferences, (iii) use of the Centers for Disease Control and Prevention (CDC) CD-ROM on AST, and (iv) the CDC Multilevel Antimicrobial Susceptibility Testing Resource website. The interventions could be implemented more widely in the United States to improve AST knowledge and practices.

Results of a physician survey on ordering viral load testing. Opportunity for laboratory consultation.

OBJECTIVE: To profile physicians' practices, utilization, and understanding of human immunodeficiency virus type 1 RNA (viral load) testing and the laboratory's role in this testing. DESIGN: Cross sectional study using a 34-item self-report survey mailed to physicians identified as requesting viral load testing, with follow-up mailings to nonresponders. PARTICIPANTS: A sampling of US physicians specializing in infectious diseases, internal medicine, and family practice associated with high, medium, and low human immunodeficiency virus/acquired immunodeficiency syndrome incidence areas. RESULTS: Most respondents using viral load results were infectious diseases specialists practicing in urban areas. The reasons most frequently given for requesting viral load testing were (1) to assist in patient follow-up or monitoring (75.4%), and (2) to initiate/guide therapy (62.5%). Respondents indicated that the interpretation and use of viral load results presented difficulty in the areas of patient treatment and in determining what change from baseline was clinically significant. Few respondents used the testing laboratory pathologist as a resource for interpreting viral load test results. CONCLUSIONS: Our study indicates that physicians have questions about (1) the meaning of viral load tests, (2) how often to monitor the viral load, and (3) what change from baseline of the viral load is significant. Few physicians avail themselves of the expertise available in the laboratory for testing viral loads and interpreting such results.

Core functions and capabilities of state public health laboratories: a report of the Association of Public Health Laboratories.

Emerging natural and man-made threats to the health of the nations population require development of a seamless laboratory network to address preventable health risks; this can be achieved only by defining the role of public health laboratories in public and private laboratory service delivery. Establishing defined core functions and capabilities for state public health laboratories will provide a basis for assessing and improving quality laboratory activities. Defining public health laboratory functions in support of public health programs is the beginning of the process of developing performance standards for laboratories, against which state public health laboratories, and eventually local public health and clinical laboratories, will establish and implement best laboratory practices. Public health is changing, and as apart of that change, public health laboratories must advocate for and implement improvements for public health testing and surveillance. These changes are outlined also in the Association of Public Health Laboratories consensus report (Association of Public Health Laboratories. Core functions and capabilities of state public health laboratories: a white paper for use in understanding the role and value of public health laboratories in protecting our nation's health. Washington, DC: Association of Public Health Laboratories, 2000).

HIV-1 antiretroviral resistance testing laboratories.

OBJECTIVE: To identify and to describe the genotyping and the phenotyping testing practices of U.S. laboratories performing patient HIV-1 antiretroviral resistance testing. DESIGN: A self-report 44-item mailed questionnaire. PARTICIPANTS: Laboratories potentially performing HIV-1 antiretroviral resistance testing. MAIN OUTCOME MEASURE: Descriptive study. RESULTS: Of 236 laboratories surveyed, 165 (69.9%) returned completed surveys, but only 23 performed HIV-1 antiretroviral resistance testing. Most were university hospitals (47.8%) or independent laboratories (26.1%). All 23 laboratories used genotypic methods, while nine (39.1%) used both genotyping and phenotyping. Most testing was used for clinical trials or laboratory research. The amount of patient information collected by laboratories varied, as did their type of quality assurance measures. Variation was found with regard to: testing volume, testing experience, testing reasons, testing methods availability, testing controls, specimen treatment, and storage stability. CONCLUSIONS: Due to variation in practices in this area of patient testing, it may be advantageous for laboratory professionals to reach a consensus on what is the most acceptable.