Longitudinal Qualitative and Quantitative Evaluation of SARS-CoV-2 Antibodies in Immunized Health Care Workers.

CONTEXT.­: Many studies have depended on qualitative antibody assays to investigate questions related to COVID-19 infection, vaccination, and treatment. OBJECTIVE.­: To evaluate immunoglobulin G (IgG) levels in vaccinated individuals over time and characterize limitations of qualitative and quantitative antibody assays. DESIGN.­: Longitudinal serum samples (n = 339) were collected from 72 health care workers vaccinated against COVID-19. SARS-CoV-2 IgG levels before, during, and after vaccination were measured by using a qualitative anti-spike protein IgG assay and a quantitative anti-S1 IgG assay. Assay results were compared to understand antibody dynamics related to vaccination. RESULTS.­: Qualitative testing demonstrated 100% seroconversion after the first vaccine dose, peak IgG levels after the second vaccine dose, and a progressive 50% decline during the next 8 months. Quantitative testing demonstrated that IgG levels during and after vaccination were above the analytical measurement range. CONCLUSIONS.­: Qualitative testing demonstrates expected changes in SARS-CoV-2 IgG levels related to sequential vaccine doses and time since antigen exposure. However, proportional changes in the associated numerical signals are very likely inaccurate. Adoption of standardized quantitative SARS-CoV-2 antibody testing with a broad analytical measurement range is essential to determine a correlate of protection from COVID-19 that can be scaled for widespread use.

Creation of a Quality Payment Program Measure for Mismatch Repair or Microsatellite Instability Biomarker Testing Status in Colorectal, Endometrial, Gastroesophageal, or Small Bowel Carcinoma.

CONTEXT.­: Quality measures that are supported by evidence-based clinical practice guidelines are preferred for assessing the quality of pathologists' practices. Careful testing of a measure ensures that scores obtained by that measure reflect the quality of a pathologist's practice. OBJECTIVE.­: To specify a new quality measure and to demonstrate through testing that it is suitable for measuring pathologists' appropriate incorporation of information regarding microsatellite instability (MSI) and/or mismatch repair (MMR) status in pathology reports for colorectal, endometrial, gastroesophageal, and small bowel carcinoma. DESIGN.­: The College of American Pathologists collaborated with the American Gastroenterological Association to specify and test the new measure. Face validity testing was used to investigate the validity of the measure. Feasibility testing was conducted to understand if data elements required by the measure specification were readily accessible. Signal-to-noise analysis was used to characterize the measure's reliability. RESULTS.­: Guideline recommendations for MSI and/or MMR testing supported specifications for the measure. Face validity testing indicated that the measure could distinguish the quality of care provided. Data elements required by the measure specification were found to be accessible, which supported the measure's feasibility. Reliability testing showed that differences in measure score were attributable to real differences in performance rather than random variation in scoring. CONCLUSIONS.­: The Mismatch Repair or Microsatellite Instability Biomarker Testing Status in Colorectal Carcinoma, Endometrial, Gastroesophageal, or Small Bowel Carcinoma measure was appropriately specified, and testing demonstrated that it is well suited for characterizing the quality of pathologists' communication of MMR and/or MSI status.

ABO Blood Groups Are Not Associated With COVID-19 Disease Incidence and Severity When Correcting for Ethnicity Differences in Blood Type.

OBJECTIVES: To determine if blood type is a risk factor for coronavirus disease 2019 (COVID-19) disease incidence and severity after correcting for ethnicity differences between novel infections and known ABO blood type frequency differences. METHODS: We performed a retrospective analysis on all severe acute respiratory system coronavirus 2 (SARS-CoV-2) infections and disease severity across two major testing sites in Colorado. We evaluated all individuals with a SARS-CoV-2 nucleic acid test (NAT) and a known blood type between March 1, 2020, and June 1, 2020. We then created a prediction algorithm based on the corrected blood types by ethnicity using data from the Colorado Department of Health and established blood types by ethnicity. We applied this prediction algorithm to all patients in our sample. RESULTS: Of 8,676 patients, 485 (5.6%) had a positive SARS-CoV-2 NAT test and 8,191 (94.4%) had a negative test. All patients had ABO blood types that mirrored the expected blood type distribution within the state of Colorado (P = .15, χ 2 statistic = 5.31). No differences in expected blood groups were present between ethnicity-adjusted SARS-CoV-2-negative and SARS-CoV-2-positive patients (χ 2 = 3.416313, P = .332). CONCLUSIONS: Blood type is not associated with COVID-19 disease incidence or severity after correcting for ethnicity differences in expected blood type frequencies.

Laboratory Detection and Initial Diagnosis of Monoclonal Gammopathies.

CONTEXT.­: The process for identifying patients with monoclonal gammopathies is complex. Initial detection of a monoclonal immunoglobulin protein (M protein) in the serum or urine often requires compilation of analytical data from several areas of the laboratory. The detection of M proteins depends on adequacy of the sample provided, available clinical information, and the laboratory tests used. OBJECTIVE.­: To develop an evidence-based guideline for the initial laboratory detection of M proteins. DESIGN.­: To develop evidence-based recommendations, the College of American Pathologists convened a panel of experts in the diagnosis and treatment of monoclonal gammopathies and the laboratory procedures used for the initial detection of M proteins. The panel conducted a systematic literature review to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, recommendations were created based on the available evidence, strength of that evidence, and key judgements as defined in the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework. RESULTS.­: Nine guideline statements were established to optimize sample selection and testing for the initial detection and quantitative measurement of M proteins used to diagnose monoclonal gammopathies. CONCLUSIONS.­: This guideline was constructed to harmonize and strengthen the initial detection of an M protein in patients displaying symptoms or laboratory features of a monoclonal gammopathy. It endorses more comprehensive initial testing when there is suspicion of amyloid light chain amyloidosis or neuropathies, such as POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome, associated with an M protein.

Developing Pathology Measures for the Quality Payment Program-Part I: A Quest for Meaningful Measures.

CONTEXT.­: Quality measures assess health care processes, outcomes, and patient perceptions associated with high-quality health care, which is commonly defined as care that is effective, safe, efficient, patient centered, equitable, and timely. Such measures are now being used in order to incentivize provision of high-quality health care. OBJECTIVE.­: To meet the goals of the Quality Payment Program, quality measures will be developed from clinical practice guidelines and relevant, peer-reviewed research identifying evidence that the measure addresses 3 areas: a high-priority aspect of health care or a specific national health goal or priority; a meaningful focus, such as leading to a desired health outcome; and a gap or variation in care. DESIGN.­: Within the College of American Pathologists (CAP), the Measures and Performance Assessment Subcommittee is tasked with developing useful performance measures. Participating practitioners can then select measures that are meaningful to their respective patients and practices, and reflect the quality of the services they provide. RESULTS.­: The CAP developed 23 quality measures for reporting to the Centers for Medicare & Medicaid Services that reflect rigorous clinical evidence and address areas in need of performance improvement. CONCLUSIONS.­: Because the implications of reporting on these pathology-specific metrics are significant, these measures and the process by which they were designed are presented here in peer-reviewed fashion. The measures described in this article (part 1) represent recent efforts by the CAP to develop meaningful measures that reflect rigorous clinical evidence and highlight areas with opportunities for performance improvement.

DNA-Based versus RNA-Based Detection of MET Exon 14 Skipping Events in Lung Cancer.

INTRODUCTION: Genomic variants that lead to MET proto-oncogenem receptor tyrosine kinase (MET) exon 14 skipping represent a potential targetable molecular abnormality in NSCLC. Consequently, reliable molecular diagnostic approaches that detect these variants are vital for patient care. METHODS: We screened tumor samples from patients with NSCLC for MET exon 14 skipping by using two distinct approaches: a DNA-based next-generation sequencing assay that uses an amplicon-mediated target enrichment and an RNA-based next-generation sequencing assay that uses anchored multiplex polymerase chain reaction for target enrichment. RESULTS: The DNA-based approach detected MET exon 14 skipping variants in 11 of 856 NSCLC samples (1.3%). The RNA-based approach detected MET exon 14 skipping in 17 of 404 samples (4.2%), which was a statistically significant increase compared with the DNA-based assay. Among 286 samples tested by both assays, RNA-based testing detected 10 positives, six of which were not detected by the DNA-based assay. Examination of primer binding sites in the DNA-based assay in comparison with published MET exon 14 skipping variants revealed genomic deletion involving primer binding sequences as the likely cause of false negatives. Two samples positive via the DNA-based approach were uninformative via the RNA-based approach due to poor-quality RNA. CONCLUSIONS: By circumventing an inherent limitation of DNA-based amplicon-mediated testing, RNA-based analysis detected a higher proportion of MET exon 14 skipping cases. However, RNA-based analysis was highly reliant on RNA quality, which can be suboptimal in some clinical samples.

Quality Control Practices for Chemistry and Immunochemistry in a Cohort of 21 Large Academic Medical Centers.

OBJECTIVES: In the United States, minimum standards for quality control (QC) are specified in federal law under the Clinical Laboratory Improvement Amendment and its revisions. Beyond meeting this required standard, laboratories have flexibility to determine their overall QC program. METHODS: We surveyed chemistry and immunochemistry QC procedures at 21 clinical laboratories within leading academic medical centers to assess if standardized QC practices exist for chemistry and immunochemistry testing. RESULTS: We observed significant variation and unexpected similarities in practice across laboratories, including QC frequency, cutoffs, number of levels analyzed, and other features. CONCLUSIONS: This variation in practice indicates an opportunity exists to establish an evidence-based approach to QC that can be generalized across institutions.

A Primer on Health Economic Evaluations in Thoracic Oncology.

There is growing interest for economic evaluation in oncology to illustrate the value of multiple new diagnostic and therapeutic interventions. As these analyses have started to move from specialist publications into mainstream medical literature, the wider medical audience consuming this information may need additional education to evaluate it appropriately. Here we review standard practices in economic evaluation, illustrating the different methods with thoracic oncology examples where possible. When interpreting and conducting health economic studies, it is important to appraise the method, perspective, time horizon, modeling technique, discount rate, and sensitivity analysis. Guidance on how to do this is provided. To provide a method to evaluate this literature, a literature search was conducted in spring 2015 to identify economic evaluations published in the Journal of Thoracic Oncology. Articles were reviewed for their study design, and areas for improvement were noted. Suggested improvements include using more rigorous sensitivity analyses, adopting a standard approach to reporting results, and conducting complete economic evaluations. Researchers should design high-quality studies to ensure the validity of the results, and consumers of this research should interpret these studies critically on the basis of a full understanding of the methodologies used before considering any of the conclusions. As advancements occur on both the research and consumer sides, this literature can be further developed to promote the best use of resources for this field.