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.

Trends in the use of cervical cancer screening tests in a large medical claims database, United States, 2013-2019.

OBJECTIVE: To examine trends in the use of cervical cancer screening tests during 2013-2019 among commercially insured women. METHODS: The study population included women of all ages with continuous enrollment each year in the IBM MarketScan commercial or Medicare supplemental databases and without known history of cervical cancer or precancer (range = 6.9-9.8 million women per year). Annual cervical cancer screening test use was examined by three modalities: cytology alone, cytology plus HPV testing (cotesting), and HPV testing alone. Trends were assessed using 2-sided Poisson regression. RESULTS: Use of cytology alone decreased from 34.2% in 2013 to 26.4% in 2019 among women aged 21-29 years (P < .0001). Among women aged 30-64 years, use of cytology alone decreased from 18.9% in 2013 to 8.6% in 2019 (P < .0001), whereas cotesting use increased from 14.9% in 2013 to 19.3% in 2019 (P < .0001). Annual test use for HPV testing alone was below 0.5% in all age groups throughout the study period. Annually, 8.7%-13.6% of women aged 18-20 years received cervical cancer screening. There were persistent differences in screening test use by metropolitan residence and census regions despite similar temporal trends. CONCLUSIONS: Temporal changes in the use of cervical cancer screening tests among commercially insured women track changes in clinical guidelines. Screening test use among individuals younger than 21 years shows that many young women are inappropriately screened for cervical cancer.

Mapping of the US Domestic Influenza Virologic Surveillance Landscape.

Influenza virologic surveillance is critical each season for tracking influenza circulation, following trends in antiviral drug resistance, detecting novel influenza infections in humans, and selecting viruses for use in annual seasonal vaccine production. We developed a framework and process map for characterizing the landscape of US influenza virologic surveillance into 5 tiers of influenza testing: outpatient settings (tier 1), inpatient settings and commercial laboratories (tier 2), state public health laboratories (tier 3), National Influenza Reference Center laboratories (tier 4), and Centers for Disease Control and Prevention laboratories (tier 5). During the 2015-16 season, the numbers of influenza tests directly contributing to virologic surveillance were 804,000 in tiers 1 and 2; 78,000 in tier 3; 2,800 in tier 4; and 3,400 in tier 5. With the release of the 2017 US Pandemic Influenza Plan, the proposed framework will support public health officials in modeling, surveillance, and pandemic planning and response.

Evaluation of Diverse Health Professionals' Learning Experience in a Continuing Education Activity for Quality Practices in Molecular Genetic Testing.

OBJECTIVE: This study was conducted to evaluate the responses of 3,265 health professionals who took a continuing education (CE) activity during June 2009 - April 2012 for a comprehensive set of good laboratory practice recommendations for molecular genetic testing. DESIGN: Participants completed an evaluation questionnaire as part of the CE activity. Responses were summarized to assess the participants' learning outcomes and commitment to applying the knowledge gained. PARTICIPANTS: Participants included nurses (47%), laboratory professionals (18%), physicians (14%), health educators (4%), public health professionals (2%), office staff (1%), and other health professionals (10%). RESULTS: Only 32% of all participants correctly answered all 12 open-book knowledge-check questions, ranging from 4 to 42% among the different professional groups (P<0.0001). However, over 80% of all participants expressed confidence in describing the practice recommendations, and 75% indicated the recommendations would improve the quality of their practice. Developing health education materials and local practice guidelines represented the common areas in which participants planned to use the knowledge gained (49% and 18% of all participants, respectively). CONCLUSION: Despite perceived self-efficacy in most participants, as high as 68% did not fully use the learning materials provided to answer the knowledge-check questions. These findings suggest the need for improved CE activities that motivate effective learning and address the specific needs of different health professions.

Use of the prostate-specific antigen (PSA) test in the United States for men age ≥65, 1999-2015: Implications for practice interventions.

BACKGROUND: Various professional organizations have issued recommendations on use of the PSA test to screen for prostate cancer in different age groups. AIMS: Using Medicare claims databases, we aimed to determine rates of PSA testing in the context of screening recommendations during 1999-2015 for US men age ≥65, stratified by age group and census regions, after excluding claims relating to all prostate-related conditions. METHODS AND RESULTS: Medicare claims databases encompassed 9.71-11.12 million men for the years under study. PSA testing rate was the proportion of men with ≥1 test(s) per 12 months of continuous enrollment. Men diagnosed with any prostate-related condition were excluded. Annual percent change (APC) in PSA test use was estimated using joinpoint regression analysis. In 1999-2015, annual testing rate was 10.1%-23.1%, age ≥85; 16.6%-31.0%, age 80-84; 23.8%-35.8%, age 75-79; 28.3%-36.9%, age 70-74; and 26.4%-33.6%, age 65-69. From 1999 to 2015, PSA testing rate decreased 40.7%, 29.9%, 13.9%, and 2.9%, respectively, for men age ≥85, 80-84, 75-79, and 70-74. For men age 65-69, test use increased by 0.3%. Significant APC trends were: APC1999-2002  = +8.1%, P = .029 and APC2008-2015  = -9.0%, P < .001 for men age ≥85; APC2008-2015  = -7.1%, P = .001 for men age 80-84; APC2001-2015  = -2.5%, P < .001 for men age 75-79; APC2008-2015  = -3.3%, P = .007 for men age 70-74; and APC2010-2015  = -5.2%, P = .014 for men age 65-69. COCLUSION: Although decreased from 1999 to 2015, PSA testing rates remained high for men age ≥70. Further research could help understand why PSA testing continues inconsistent with recommendations.

Use of the prostate-specific antigen test in the U.S. for men age 30 to 64 in 2011 to 2017 using a large commercial claims database: Implications for practice interventions.

BACKGROUND: Given the public health relevance of PSA-based screening, various professional organizations have issued recommendations on the use of the PSA test to screen for prostate cancer in different age groups. AIM: Using a large commercial claims database, we aimed to determine the most recent rates of PSA testing for privately insured men age 30 to 64 in the context of screening recommendations. METHODS AND RESULTS: Data from employer plans were from MarketScan commercial claims database. Annual PSA testing rate was the proportion of men with ≥1 paid test(s) per 12 months of continuous enrollment. Men with diagnosis of any prostate-related condition were excluded. Annual percent change (APC) in PSA test use was estimated using joinpoint regression analysis. In 2011 to 2017, annual testing rate encompassing 5.02 to 5.53 million men was approximately 1.4%, age 30 to 34; 3.4% to 4.1%, age 35 to 39; 11% to 13%, age 40 to 44; 18% to 21%, age 45 to 49; 31% to 33%, age 50 to 54; 35% to 37%, age 55 to 59; and 38% to 41%, age 60 to 64. APC for 2011 to 2017 was -0.5% (P = .11), age 30 to 34; -3.0% (P = .001), age 35-39; -3.1% (P < .001), age 40 to 44; -2.4% (P = .001), age 45 to 49; -0.2% (P = .66), age 50 to 54; 0.0% (P = .997), age 55 to 59; and -3.3% (P = .054) from 2011 to 2013 and 1.2% (P = .045) from 2013 to 2017, age 60 to 64. PSA testing rate decreased from 2011 to 2017 for age groups between 35 and 49 by 13.4% to 16.9%. CONCLUSIONS: Based on these data, PSA testing rate has modestly decreased from 2011 to 2017. These results, however, should be considered in view of the limitation that MarketScan claims data may not be equated to actual PSA testing practices in the entire U.S. population age 30 to 64. Future research should be directed to understand why clinicians continue ordering PSA test for men younger than 50.

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.

Good laboratory practices for molecular genetic testing for heritable diseases and conditions.

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations, laboratory testing is categorized as waived (from routine regulatory oversight) or nonwaived based on the complexity of the tests; tests of moderate and high complexity are nonwaived tests. Laboratories that perform molecular genetic testing are subject to the general CLIA quality systems requirements for nonwaived testing and the CLIA personnel requirements for tests of high complexity. Although many laboratories that perform molecular genetic testing comply with applicable regulatory requirements and adhere to professional practice guidelines,specific guidelines for quality assurance are needed to ensure the quality of test performance. To enhance the oversight of genetic testing under the CLIA framework,CDC and the Centers for Medicare & Medicaid Services (CMS) have taken practical steps to address the quality management concerns in molecular genetic testing,including working with the Clinical Laboratory Improvement Advisory Committee (CLIAC). This report provides CLIAC recommendations for good laboratory practices for ensuring the quality of molecular genetic testing for heritable diseases and conditions. The recommended practices address the total testing process (including the preanalytic,analytic,and postanalytic phases),laboratory responsibilities regarding authorized persons,confidentiality of patient information,personnel competency,considerations before introducing molecular genetic testing or offering new molecular genetic tests,and the quality management system approach to molecular genetic testing. These recommendations are intended for laboratories that perform molecular genetic testing for heritable diseases and conditions and for medical and public health professionals who evaluate laboratory practices and policies to improve the quality of molecular genetic laboratory services. This report also is intended to be a resource for users of laboratory services to aid in their use of molecular genetic tests and test results in health assessment and care. Improvements in the quality and use of genetic laboratory services should improve the quality of health care and health outcomes for patients and families of patients.

IQLM and CLMA take a snapshot of America's hospital laboratory quality management.

CLMA volunteered to conduct an online pilot survey of its membership to help the Institute for Quality in Laboratory Medicine (IQLM) determine quality management activities in laboratories. Among the hospital-based members who were surveyed, approximately 25 percent responded. The data they volunteered provide a snapshot of the current state of laboratory quality management. The pilot survey is part of a larger IQLM plan to develop networks of laboratories to monitor and evaluate laboratory practices and services to enhance laboratory medicine. This pilot survey will be used by IQLM as a model to establish quality and patient safety networks, applicable to laboratories of all sizes and types. Performance comparisons and best practices may then be shared to reduce laboratory errors and improve patient safety.

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.

Laboratory medicine quality indicators: a review of the literature.

We summarize information on quality indicators related to laboratory testing from published literature and Internet sources to assess current gaps with respect to stages of the laboratory testing process, the Institute of Medicine (IOM) health care domains, and quality measure evaluation criteria. Our search strategy used various general and specific terms for clinical conditions and laboratory procedures. References related to a potential quality indicator associated with laboratory testing and an IOM health care domain were included. With the exception of disease- and condition-related indicators originating from clinical guidelines, the laboratory medicine quality indicators reviewed did not satisfy minimum standard evaluation criteria for quality or performance measures (ie, importance, scientific acceptability, and feasibility) and demonstrated a need across the total laboratory testing process for consistently specified, useful, and evidence-based, laboratory-related quality and performance measures that are important to health outcomes and meaningful to health care stakeholders for which laboratories can be held accountable.

A summary of deliberations on strategic planning for continuous quality improvement in laboratory medicine.

On September 24-26, 2007, the Centers for Disease Control and Prevention convened the 2007 Institute on Critical Issues in Health Laboratory Practice: Managing for Better Health to develop an action plan for change for the immediate and long-term future. A wide variety of stakeholders, including pathologists, pathologist extenders, clinicians, and researchers, examined means to improve laboratory service communication, quality parameters, and potential future laboratory contributions to health care. In this summary document, we present the identified gaps, barriers, and proposed action plans for improvement for laboratory medicine in the 6 quality domains identified by the Institute of Medicine: safety, effectiveness, patient centeredness, timeliness, efficiency, and equity. Five major recommendations emerged from concluding discussions and included focusing on preanalytic and postanalytic processes as areas of potential quality improvement and recruiting a multidisciplinary group of nonlaboratory stakeholders to work with laboratory personnel to achieve improvement goals.

Results of a survey of hospital coagulation laboratories in the United States, 2001.

CONTEXT: Coagulation and bleeding problems are associated with substantial morbidity and mortality, and inappropriate testing practices may lead to bleeding or thrombotic complications. OBJECTIVE: To evaluate practices reported by hospital coagulation laboratories in the United States and to determine if the number of beds in a hospital was associated with different practices. DESIGN: From a sampling frame of institutions listed in the 1999 directory of the American Hospital Association, stratified into hospitals with 200 or more beds ("large hospitals") and those with fewer than 200 beds ("small hospitals"), we randomly selected 425 large hospitals (sampling rate, 25.6%) and 375 small hospitals (sampling rate, 8.8%) and sent a survey to them between June and October 2001. Of these, 321 large hospitals (75.5%) and 311 small hospitals (82.9%) responded. RESULTS: An estimated 97.1% of respondents reported performing some coagulation laboratory tests. Of these, 71.6% reported using 3.2% sodium citrate as the specimen anticoagulant to determine prothrombin time (81.3% of large vs 67.7% of small hospitals, P < .001). Of the same respondents, 45.3% reported selecting thromboplastins insensitive to heparin in the therapeutic range when measuring prothrombin time (59.4% of large vs 39.8% of small hospitals, P < .001), and 58.8% reported having a therapeutic range for heparin (72.9% of large vs 53.2% of small hospitals, P < .001). An estimated 96.3% of respondents assayed specimens for activated partial thromboplastin time within 4 hours after phlebotomy, and 89.4% of respondents centrifuged specimens within 1 hour of collection. An estimated 12.1% reported monitoring low-molecular-weight heparin therapy, and to do so, 79% used an assay for activated partial thromboplastin time (58% of large vs 96% of small hospitals, P = .001), whereas 38% used an antifactor Xa assay (65% of large vs 18% of small hospitals, P = .001). CONCLUSIONS: Substantial variability in certain laboratory practices was evident. Where significant differences existed between the hospital groups, usually large hospitals adhered to accepted practice guidelines to a greater extent. Some reported practices are not consistent with current recommendations, showing a need to understand the reasons for noncompliance so that better adherence to accepted standards of laboratory practice can be promoted.