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.

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.

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.

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.

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 534ng/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.

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.

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.

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.

As an external assessment of quality, proficiency testing (PT) is recognized as one essential component for assuring quality testing in clinical laboratories.1–3 Each laboratory that performs non-waived testing is required by the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform PT. The CLIA regulations specify requirements for PT program provider approval by the Department of Health and Human Services (HHS). | | The CLIA law changed the paradigm for providers from an educational to a more regulatory role. Consequently, there are often misperceptions about providers’ operations and their limitations. This report presents some of the common viewpoints held by clinical laboratory professionals and the corresponding perspectives shared by some PT providers. The report is intended to assist clinical laboratories in understanding the constraints faced by PT program providers, learning about potentially helpful provider services, communicating with their providers, and making knowledgeable inquiries as they search for PT services. | | In 2012, the Centers for Disease Control and Prevention (CDC), working in collaboration with the Association of Public Health Laboratories, conducted a series of focus groups that included clinical and public health laboratory professionals to explore how they use and perceive PT.4–5 Some discussions concerned participants’ satisfaction with PT provider services. Participants spoke of issues they had experienced and made recommendations for providers to consider. As a follow-up to the focus groups, in 2015 CDC developed several open-ended questions about some of these issues and sent them to all 11 HHS-approved PT program providers that provide, at a minimum, chemistry analytes. Seven providers furnished either written or verbal answers, which are summarized in this article. Respondents included providers which offer a wide range of programs: programs affiliated with accreditation organizations; those that offer a small number of programs to specific types of laboratories (e.g. physician office laboratories); and some independent and state-affiliated programs.

Along with requirements for personnel qualifications and quality control testing, proficiency testing (PT) is one of the central safeguards of laboratory quality under the Clinical Laboratory Improvement Amendments of 1988 (CLIA)1 and its regulations.2 The CLIA regulations have often been compared to a three-legged stool, resting on requirements for personnel qualifications and two performance indicators: quality control testing and proficiency testing. Proficiency testing is the only external performance indicator required by CLIA.

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.

We commend Don-Wauchope et al., who assessed 11 National Academy of Clinical Biochemistry (NACB)1 laboratory medicine practice guidelines (LMPGs) with the AGREE II (Appraisal of Guidelines for Research and Evaluation II) instrument (1), and we thank Bossuyt for his accompanying editorial (2). The results of this study are helpful but are not unexpected. These LMPGs were developed over several years. The 8 nonarchived LMPGs published in the past 5 years used 4 different systems for grading and weighting practice recommendations. One system that several LMPG committees have used is a modified US Preventive Services Task Force (USPSTF) system. A second system used for 2 LMPGs was that of the American College of Cardiology and the American Heart Association. At times, NACB LMPG committees have used clinical societies' systems when these groups are primary collaborators in LMPG development, as well as significant end users of the LMPG. A third system created by the authors of 3 LMPGs focused on tumor marker tests. This unique system was developed by LMPG members who felt that considerable heterogeneity in clinical oncology practice guidelines failed to indicate a preference in any clinical society's system. Finally, authors of the most recent diabetes LMPG created a unique system based on various extant models, including the USPSTF system and the GRADE instrument, to develop a methodology that would be more applicable to selecting laboratory tests in clinical practice. Although all approaches were designed to be transparent and fair, the lack of a systematic approach in the methodology systems used is one of several potential reasons for the disparity in the LMPG scores reported by Don-Wauchope et al.

We present a statistical summary of results from the Model Performance Evaluation Program (MPEP) for Mycobacterium tuberculosis Drug Susceptibility Testing, 1994-2008 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 anti-tuberculosis 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-sq p<0.0001). For resistant strains, overall agreement by methods was: AP 91.3%; BACTEC 93.0%; and MGIT 82.6% and by drugs was: INH 92.2%; RMP 91.5%; EMB 79.0%; and PZA 97.5%. 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 inter-laboratory 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.

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.

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.

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.

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.