Ethical Checklists for Clinical Research Projects and laboratory medicine: two tools to evaluate compliance with bioethical principles in different settings.

OBJECTIVES: To develop two ethical checklists to evaluate (i) management of ethical concerns in research projects and (ii) awareness of ethical conduct of healthcare laboratory professionals. METHODS: Comprehensive discussion among the members of IFCC Task Force on Ethics based on pertinent literature. RESULTS: This Checklist for Clinical Research Projects should be useful to evaluate research proposals from an ethical perspective before submitting it to an IRB or its equivalent, thereby diminishing rejection rates and resulting in more time-effective projects. The checklist designed to evaluate the ethical conduct in laboratory medicine could be useful for self evaluation (internal audits) and for certification/accreditation processes performed by third parties. CONCLUSIONS: These checklists are simple but powerful tools useful to guide professionals to adhere to ethical principles in their practice, especially in developing countries where accredited ethics committees may be difficult to find.

Tennessee hospital noncompliance with price transparency legislation for 8 common laboratory tests.

OBJECTIVES: The goal of this study was to assess hospital compliance with federal price transparency mandates and barriers to pricing information in Tennessee. METHODS: All hospitals websites were queried for gross, cash, and BlueCross BlueShield of Tennessee prices for 8 high-frequency laboratory tests in 2 Centers for Medicare & Medicaid Services-mandated pricing sources: (1) a machine-readable file of all available services and (2) a consumer-friendly display of 300 shoppable services. Barriers, including click counts, data availability, and intrahospital price discrepancies, were noted. RESULTS: Of the 145 Tennessee hospitals assessed, 97.2% were noncompliant with the Centers for Medicare & Medicaid Services final rule. Subanalysis of available machine-readable files, price estimators, and shoppable services files demonstrated 49.6%, 95.1%, and 78.6% noncompliance, respectively. Barriers to pricing information included requiring protected health information (55.9%), missing at least 1 pricing source (7.6%), having no pricing sources available (6.2%), and involving more than 3 clicks to access the cash price in machine-readable files (54.1%) and price estimators (68.6%.) Average intrahospital discrepancy for basic metabolic panel cash prices across pricing sources was $101.30 (range, $0-1012.40). CONCLUSIONS: Our study showed high levels of noncompliance with price transparency laws, inconsistent and inaccessible pricing, and continued challenges facing patients in Tennessee.

Spironolactone metabolite causes falsely increased progesterone in the Abbott Architect immunoassay.

BACKGROUND: Immunoassays are important for routine clinical testing and medical diagnosis. However, they are limited by cross-reactivity especially at low analyte concentrations. There is a critical need to investigate compounds that can interfere with immunoassays. Herein, we describe the identification of canrenone, a spironolactone metabolite that falsely increases progesterone concentrations on the Abbott Architect i2000 Immunoassay. METHODS: Serum samples and assay diluents were spiked with spironolactone or canrenone and progesterone concentrations were measured on the Architect i2000 and Immulite XPi immunoassay platforms. Blood samples from patients taking spironolactone were analyzed with liquid chromatography-tandem mass spectrometry to evaluate the intrinsic response of progesterone concentrations to the presence of canrenone. RESULTS: We measured approximately 10-fold higher progesterone concentrations on the Abbott Architect i2000 compared to reference immunoassay analyzers (Siemens Immulite XPi and Roche Cobas e601/602), suggesting an analytical error which is unique to the Architect i2000 antibody and/or assay conditions. By measuring serum progesterone after addition of spironolactone or canrenone to serum samples, we found that canrenone falsely increased progesterone on the Architect i2000 immunoassay. However, this interference was more pronounced at low serum progesterone concentrations. Moreover, a strong positive correlation was seen between canrenone and measured serum progesterone concentrations. CONCLUSIONS: Our investigations are important for individuals who require progesterone measurements using the Architect i2000 immunoassay, especially because it is unlikely for clinicians to order canrenone measurements alongside progesterone measurements for individuals taking spironolactone. Further research is needed to determine whether canrenone can influence progesterone measurements on other immunoassay systems.

Performance of Three Anti-SARS-CoV-2 Anti-S and One Anti-N Immunoassays for the Monitoring of Immune Status and Vaccine Response.

This study aimed to evaluate and compare the performance of three anti-S and one anti-N assays that were available to the project in detecting antibody levels after three commonly used SARS-CoV-2 vaccines (Pfizer, Moderna, and Johnson & Johnson). It also aimed to assess the association of age, sex, race, ethnicity, vaccine timing, and vaccine side effects on antibody levels in a cohort of 827 individuals. In September 2021, 698 vaccinated individuals donated blood samples as part of the Association for Diagnostics & Laboratory Medicine (ADLM) COVID-19 Immunity Study. These individuals also participated in a comprehensive survey covering demographic information, vaccination status, and associated side effects. Additionally, 305 age- and gender-matched samples were obtained from the ADLM 2015 sample bank as pre-COVID-19-negative samples. All these samples underwent antibody level analysis using three anti-S assays, namely Beckman Access SARS-CoV-2 IgG (Beckman assay), Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG (Ortho assay), Siemens ADVIA Centaur SARS-CoV-2 IgG (Siemens assay), and one anti-N antibody assay: Bio-Rad Platelia SARS-CoV-2 Total Ab assay (BioRad assay). A total of 827 samples (580 COVID-19 samples and 247 pre-COVID-19 samples) received results for all four assays and underwent further analysis. Beckman, Ortho, and Siemens anti-S assays showed an overall sensitivity of 99.5%, 97.6%, and 96.9%, and specificity of 90%, 100%, and 99.6%, respectively. All three assays indicated 100% sensitivity for individuals who received the Moderna vaccine and boosters, and over 99% sensitivity for the Pfizer vaccine. Sensitivities varied from 70.4% (Siemens), 81.5% (Ortho), and 96.3% (Beckman) for individuals who received the Johnson & Johnson vaccine. BioRad anti-N assays demonstrated 46.2% sensitivity and 99.25% specificity based on results from individuals with self-reported infection. The highest median anti-S antibody levels were measured in individuals who received the Moderna vaccine, followed by Pfizer and then Johnson & Johnson vaccines. Higher anti-S antibody levels were significantly associated with younger age and closer proximity to the last vaccine dose but were not associated with gender, race, or ethnicity. Participants with higher anti-S levels experienced significantly more side effects as well as more severe side effects (e.g., muscle pain, chills, fever, and moderate limitations) (p < 0.05). Anti-N antibody levels only indicated a significant correlation with headache. This study indicated performance variations among different anti-S assays, both among themselves and when analyzing individuals with different SARS-CoV-2 vaccines. Caution should be exercised when conducting large-scale studies to ensure that the same platform and/or assays are used for the most effective interpretation of the data.

College of American Pathologists Quality Cross Check -Chemistry and Therapeutic Drug Monitoring as a tool for biannual instrument correlations.

BACKGROUND: Biannual instrument-correlation studies are required for nonwaived assays performed on multiple instruments. OBJECTIVE: To determine the feasibility of using College of American Pathologists (CAP) Quality Cross Check-Chemistry and Therapeutic Drug Monitoring (CZQ) to assess instrument correlations among multiple analyzers, analyzer models, and Clinical Laboratory Improvement Amendments (CLIA) licenses for 55 unique analytes. METHODS: Instrument correlation studies were performed on 9 Abbott ARCHITECT instruments (c4000 [n = 4], c8000 [n = 2], and c16000 [n = 3]) over 3 CLIA licenses using CZQ materials. The mean (SD) values, concentration difference, percent bias, and peer data for each individual level of CZQ were determined for each individual analyzer. Acceptable concentration and percentage for each analyte were set using criteria from CAP or other reputable sources such as the American Association of Bioanalysts or the Royal College of Pathologists of Australasia. Peer data were provided by CAP with the CZQ kit. RESULTS: Correlations using CZQ materials showed that 94.5% of assays studied were within the acceptability criteria by percent bias only and 98.2% were within acceptability criteria by concentration difference. CONCLUSIONS: The use of CZQ provides support to standardized correlation studies among instruments within and across separate CLIA licenses. However, widespread adoption of CZQ may be limited due to concerns regarding matrix effects, analyte ranges, and ease of data analysis.

Large-Scale Scientific Study Led by a Professional Organization during the COVID-19 Pandemic: Operations, Best Practices, and Lessons Learned.

In 2021, the Association for Diagnostics & Laboratory Medicine (ADLM) (formerly the American Association for Clinical Chemistry [AACC]) developed a scientific study that aimed to contribute to the understanding of SARS-CoV-2 immunity during the evolving course of the pandemic. This study was led by a group of expert member volunteers and resulted in survey data from 975 individuals and blood collection from 698 of those participants. This paper describes the formulation and execution of this large-scale scientific study, encompassing best practices and insights gained throughout the endeavor.

Cannabis positivity rates in 17 emergency departments across the United States with varying degrees of marijuana legalization.

BACKGROUND: Many states in the United States have progressed towards legalization of marijuana including decriminalization, medicinal and/or recreational use. We studied the impact of legalization on cannabis-related emergency department visits in states with varying degrees of legalization. METHODS: Seventeen healthcare institutions in fifteen states (California, Colorado, Connecticut, Florida, Iowa, Kentucky, Maryland, Massachusetts, Missouri, New Hampshire, Oregon, South Carolina, Tennessee, Texas, Washington) participated. Cannabinoid immunoassay results and cannabis-related International Classification of Diseases (ninth and tenth versions) codes were obtained for emergency department visits over a 3- to 8-year period during various stages of legalization: no state laws, decriminalized, medical approval before dispensaries, medical dispensaries available, recreational approval before dispensaries and recreational dispensaries available. Trends and monthly rates of cannabinoid immunoassay and cannabis-related International Classification of Diseases code positivity were determined during these legalization periods. RESULTS: For most states, there was a significant increase in both cannabinoid immunoassay and International Classification of Diseases code positivity as legalization progressed; however, positivity rates differed. The availability of dispensaries may impact positivity in states with medical and/or recreational approval. In most states with no laws, there was a significant but smaller increase in cannabinoid immunoassay positivity rates. CONCLUSIONS: States may experience an increase in cannabis-related emergency department visits with progression toward marijuana legalization. The differences between states, including those in which no impact was seen, are likely multifactorial and include cultural norms, attitudes of local law enforcement, differing patient populations, legalization in surrounding states, availability of dispensaries, various ordering protocols in the emergency department, and the prevalence of non-regulated cannabis products.

Opportunities for recycling in an automated clinical chemistry laboratory produced by the comprehensive metabolic panel.

OBJECTIVES: Clinical laboratories perform a variety of tests for which biomedical waste is a byproduct. Of these, the complete metabolic panel (CMP) produces a significant portion of this waste. We investigated specific waste subsequent to performing CMPs over the course of a year and analyzed what percentage of the waste produced could have been recycled. METHODS: Patient testing volumes were collected retrospectively from July 14, 2021, to July 14, 2022, for individual assays within the CMP performed on Abbott Alinity c instruments (n = 6). The average weights for components of the reagent kits, which includes wedges, boxes, and package inserts, were calculated. These weights, in conjunction with total patient testing volumes, were used to determine the amount of waste produced. RESULTS: A total of 1089.2 kg of reagent kit waste was estimated to be produced by performing CMPs throughout a year. Of this waste, most (855.5 kg) was not recyclable, but a subset (233.6 kg) was. Overall, 21.4% of the total specific waste weight was found to be recyclable. CONCLUSIONS: The CMP contributes a substantial amount of waste when performed on chemistry analyzer platforms in the clinical laboratory. Paper inserts and cardboard packaging, however, presented opportunities for recycling.

T Cell Responses Correlate with Self-Reported Disease Severity and Neutralizing Antibody Responses Predict Protection against SARS-CoV-2 Breakthrough Infection.

OBJECTIVES: The objective of this prospective study was to investigate the role of adaptive immunity in response to SARS-CoV-2 vaccines. DESIGN AND METHODS: A cohort of 677 vaccinated individuals participated in a comprehensive survey of their vaccination status and associated side effects, and donated blood to evaluate their adaptive immune responses by neutralizing antibody (NAb) and T cell responses. The cohort then completed a follow-up survey to investigate the occurrence of breakthrough infections. RESULTS: NAb levels were the highest in participants vaccinated with Moderna, followed by Pfizer and Johnson & Johnson. NAb levels decreased with time after vaccination with Pfizer and Johnson & Johnson. T cell responses showed no significant difference among the different vaccines and remained stable up to 10 months after the study period for all vaccine types. In multivariate analyses, NAb responses (<95 U/mL) predicted breakthrough infection, whereas previous infection, the type of vaccine, and T cell responses did not. T cell responses to viral epitopes (<0.120 IU/mL) showed a significant association with the self-reported severity of COVID-19 disease. CONCLUSION: This study provides evidence that NAb responses to SARS-CoV-2 vaccination correlate with protection against infection, whereas the T cell memory responses may contribute to protection against severe disease but not against infection.

The impact of environmental factors on external and internal specimen transport.

The environment that a clinical specimen is exposed to is an important preanalytical factor in laboratory testing. There are numerous environmental conditions that a specimen may experience before it arrives at the clinical laboratory for analysis. Specimens collected at offsite locations are typically stored at the site and transported to the clinical laboratory via courier. Depending on the geographic location, season, method of storage and method of transport, the specimen can experience varying climate conditions that can lead to inaccurate test results. Specimens collected within the healthcare institution are not exempt from suboptimal storage and transport environments. For example, specimens transported via pneumatic tube systems can experience extreme agitation and rapid accelerations and decelerations. Suboptimal storage and transport temperatures occur less frequently within health systems due to multiple regulatory requirements for temperature monitoring; however, temperature monitoring may not occur at every stage of the preanalytical phase. This review will highlight both internal and external environmental conditions that can cause preanalytical errors in clinical laboratory testing. Strategies to mitigate environmentally-induced preanalytical errors and regulatory gaps for environmental monitoring in the preanalytical phase will also be discussed.