Challenges in the manufacture, storage, distribution and regulation of traditional and novel vaccines

Since the onset of the COVID-19 pandemic, there has been a significant surge in interest of COVID-19 vaccines in particular, and other traditional vaccines in general. This strong interest is expected to continue as the industry strives to manufacture safer and more effi cacious vaccines against COVID-19 and other infectious diseases. Vaccines are a unique class of products, being biologicals that are administered to healthy individuals to prevent diseases. The equitable distribution and availability of safe, efficacious and good quality vaccines are of utmost importance in preventing and controlling infections and safeguarding public health. The continued existence of poor- quality vaccines suggests a lack of control of manufacturing, storage, distribution, and possibly, their associated regulation. Nonetheless, all these situations - whether positive or negative, present opportunities for improvements. As regulatory authorities step up efforts in regulating existing traditional vaccines, advancements in vaccine research and development churn out novel vaccines that pose further manufacturing and regulatory challenges. This manuscript provides an overview of vaccines, both traditional and novel, and strives to identify challenges in the manufacture, storage, distribution, handling and their associated regulation. It also evaluates whether current regulatory frameworks are adequate, and where applicable, recommends areas for improvements. International harmonization and convergence of national regulatory framework with the view to facilitate quicker approval of safe, efficacious and good quality vaccines, that are accessible and affordable to patients worldwide, are also explored.

Health post COVID-19: Supranational regulatory reliance and coordination

The dominant position of the U.S. Food and Drug Administration (FDA) as the most influential regulator in the world has been particularly salient during the COVID-19 pandemic, in the context of COVID-19 vaccines' emergency use authorizations. In the context of adjustment toward a post-COVID-19 regulatory order of harmonization for medicines approval, this essay proposes a critical reflection about the justifications and political dynamics behind the FDA's power and its impact in latinamerican countries' regulatory systems, considering the already regulatory reliance on the FDA. In particular, this essay asks whether regulatory 'agility' and 'coordination' will benefit countries of the region in addressing the problems of scarcity and inequitable access to medicines that have become evident with the pandemic. © 2023 The Author(s). Oxford University Press and New York University School of Law. All rights reserved.

Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes: Design, Recruitment, and Technical Challenges of a Multicenter, Observational Neuroimaging Study.

Patients with hypoplastic left heart syndrome who have been palliated with the Fontan procedure are at risk for adverse neurodevelopmental outcomes, lower quality of life, and reduced employability. We describe the methods (including quality assurance and quality control protocols) and challenges of a multi-center observational ancillary study, SVRIII (Single Ventricle Reconstruction Trial) Brain Connectome. Our original goal was to obtain advanced neuroimaging (Diffusion Tensor Imaging and Resting-BOLD) in 140 SVR III participants and 100 healthy controls for brain connectome analyses. Linear regression and mediation statistical methods will be used to analyze associations of brain connectome measures with neurocognitive measures and clinical risk factors. Initial recruitment challenges occurred that were related to difficulties with: (1) coordinating brain MRI for participants already undergoing extensive testing in the parent study, and (2) recruiting healthy control subjects. The COVID-19 pandemic negatively affected enrollment late in the study. Enrollment challenges were addressed by: (1) adding additional study sites, (2) increasing the frequency of meetings with site coordinators, and (3) developing additional healthy control recruitment strategies, including using research registries and advertising the study to community-based groups. Technical challenges that emerged early in the study were related to the acquisition, harmonization, and transfer of neuroimages. These hurdles were successfully overcome with protocol modifications and frequent site visits that involved human and synthetic phantoms.

Assay Harmonization Study To Measure Immune Response to SARS-CoV-2 Infection and Vaccines: a Serology Methods Study.

The Coronavirus disease 2019 (COVID-19) pandemic presented the scientific community with an immediate need for accurate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology assays, resulting in an expansion of assay development, some without following a rigorous quality control and validation, and with a wide range of performance characteristics. Vast amounts of data have been gathered on SARS-CoV-2 antibody response; however, performance and ability to compare the results have been challenging. This study seeks to analyze the reliability, sensitivity, specificity, and reproducibility of a set of widely used commercial, in-house, and neutralization serology assays, as well as provide evidence for the feasibility of using the World Health Organization (WHO) International Standard (IS) as a harmonization tool. This study also seeks to demonstrate that binding immunoassays may serve as a practical alternative for the serological study of large sample sets in lieu of expensive, complex, and less reproducible neutralization assays. In this study, commercial assays demonstrated the highest specificity, while in-house assays excelled in antibody sensitivity. As expected, neutralization assays demonstrated high levels of variability but overall good correlations with binding immunoassays, suggesting that binding may be reasonably accurate as well as practical for the study of SARS-CoV-2 serology. All three assay types performed well after WHO IS standardization. The results of this study demonstrate there are high performing serology assays available to the scientific community to rigorously dissect antibody responses to infection and vaccination. IMPORTANCE Previous studies have shown significant variability in SARS-CoV-2 antibody serology assays, highlighting the need for evaluation and comparison of these assays using the same set of samples covering a wide range of antibody responses induced by infection or vaccination. This study demonstrated that there are high performing assays that can be used reliably to evaluate immune responses to SARS-CoV-2 in the context of infection and vaccination. This study also demonstrated the feasibility of harmonizing these assays against the International Standard and provided evidence that the binding immunoassays may have high enough correlation with the neutralization assays to serve as a practical proxy. These results represent an important step in standardizing and harmonizing the many different serological assays used to evaluate COVID-19 immune responses in the population.

Advances in Microbiome-Derived Solutions and Methodologies Are Founding a New Era in Skin Health and Care.

The microbiome, as a community of microorganisms and their structural elements, genomes, metabolites/signal molecules, has been shown to play an important role in human health, with significant beneficial applications for gut health. Skin microbiome has emerged as a new field with high potential to develop disruptive solutions to manage skin health and disease. Despite an incomplete toolbox for skin microbiome analyses, much progress has been made towards functional dissection of microbiomes and host-microbiome interactions. A standardized and robust investigation of the skin microbiome is necessary to provide accurate microbial information and set the base for a successful translation of innovations in the dermo-cosmetic field. This review provides an overview of how the landscape of skin microbiome research has evolved from method development (multi-omics/data-based analytical approaches) to the discovery and development of novel microbiome-derived ingredients. Moreover, it provides a summary of the latest findings on interactions between the microbiomes (gut and skin) and skin health/disease. Solutions derived from these two paths are used to develop novel microbiome-based ingredients or solutions acting on skin homeostasis are proposed. The most promising skin and gut-derived microbiome interventional strategies are presented, along with regulatory, safety, industrial, and technical challenges related to a successful translation of these microbiome-based concepts/technologies in the dermo-cosmetic industry.

A deep neural architecture for harmonizing 3-D input data analysis and decision making in medical imaging

Harmonizing the analysis of data, especially of 3-D image volumes, consisting of different number of slices and annotated per volume, is a significant problem in training and using deep neural networks in various applications, including medical imaging. Moreover, unifying the decision making of the networks over different input datasets is crucial for the generation of rich data-driven knowledge and for trusted usage in the applications. This paper presents a new deep neural architecture, named RACNet, which includes routing and feature alignment steps and effectively handles different input lengths and single annotations of the 3-D image inputs, whilst providing highly accurate decisions. In addition, through latent variable extraction from the trained RACNet, a set of anchors are generated providing further insight on the network's decision making. These can be used to enrich and unify data-driven knowledge extracted from different datasets. An extensive experimental study illustrates the above developments, focusing on COVID-19 diagnosis through analysis of 3-D chest CT scans from databases generated in different countries and medical centers.

Salud postpandemia: influencia supranacional y coordinacion regulatoria Health post COVID-19: Supranational regulatory reliance and coordination

The dominant position of the U.S. Food and Drug Administration (FDA) as the most influential regulator in the world has been particularly salient during the COVID-19 pandemic, in the context of COVID-19 vaccines' emergency use authorizations. In the context of adjustment toward a post-COVID-19 regulatory order of harmonization for medicines approval, this essay proposes a critical reflection about the justifications and political dynamics behind the FDA's power and its impact in latinamerican countries' regulatory systems, considering the already regulatory reliance on the FDA. In particular, this essay asks whether regulatory 'agility' and 'coordination' will benefit countries of the region in addressing the problems of scarcity and inequitable access to medicines that have become evident with the pandemic.

C-reactive protein and clinical outcome in COVID-19 patients: the importance of harmonized measurements.

C-reactive protein (CRP) is a cytokine-mediated acute phase reactant with a recognized role in inflammatory conditions and infectious disease. In coronavirus disease 2019 (COVID-19), elevated CRP concentrations in serum were frequently detected and significantly associated with poor outcome in terms of disease severity, need for intensive care, and in-hospital death. For these reasons, the marker was proposed as a powerful test for prognostic classification of COVID-19 patients. In most of available publications, there was however confounding information about how interpretative criteria for CRP in COVID-19 should be derived, including quality of employed assays and optimal cut-off definition. Assuring result harmonization and controlling measurement uncertainty in terms of performance specifications are fundamental to allow worldwide application of clinical information according to specific CRP thresholds and to avoid risk of patient misclassification.

A Path to Real-World Evidence in Critical Care Using Open-Source Data Harmonization Tools.

COVID-19 highlighted the need for use of real-world data (RWD) in critical care as a near real-time resource for clinical, research, and policy efforts. Analysis of RWD is gaining momentum and can generate important evidence for policy makers and regulators. Extracting high quality RWD from electronic health records (EHRs) requires sophisticated infrastructure and dedicated resources. We sought to customize freely available public tools, supporting all phases of data harmonization, from data quality assessments to de-identification procedures, and generation of robust, data science ready RWD from EHRs. These data are made available to clinicians and researchers through CURE ID, a free platform which facilitates access to case reports of challenging clinical cases and repurposed treatments hosted by the National Center for Advancing Translational Sciences/National Institutes of Health in partnership with the Food and Drug Administration. This commentary describes the partnership, rationale, process, use case, impact in critical care, and future directions for this collaborative effort.

Design and Implementation of a Collaborative Clinical Practice and Research Documentation System Using SNOMED-CT and HL7-CDA in the Context of a Pediatric Neurodevelopmental Unit.

This paper introduces a prototype for clinical research documentation using the structured information model HL7 CDA and clinical terminology (SNOMED CT). The proposed solution was integrated with the current electronic health record system (EHR-S) and aimed to implement interoperability and structure information, and to create a collaborative platform between clinical and research teams. The framework also aims to overcome the limitations imposed by classical documentation strategies in real-time healthcare encounters that may require fast access to complex information. The solution was developed in the pediatric hospital (HP) of the University Hospital Center of Coimbra (CHUC), a national reference for neurodevelopmental disorders, particularly for autism spectrum disorder (ASD), which is very demanding in terms of longitudinal and cross-sectional data throughput. The platform uses a three-layer approach to reduce components' dependencies and facilitate maintenance, scalability, and security. The system was validated in a real-life context of the neurodevelopmental and autism unit (UNDA) in the HP and assessed based on the functionalities model of EHR-S (EHR-S FM) regarding their successful implementation and comparison with state-of-the-art alternative platforms. A global approach to the clinical history of neurodevelopmental disorders was worked out, providing transparent healthcare data coding and structuring while preserving information quality. Thus, the platform enabled the development of user-defined structured templates and the creation of structured documents with standardized clinical terminology that can be used in many healthcare contexts. Moreover, storing structured data associated with healthcare encounters supports a longitudinal view of the patient's healthcare data and health status over time, which is critical in routine and pediatric research contexts. Additionally, it enables queries on population statistics that are key to supporting the definition of local and global policies, whose importance was recently emphasized by the COVID pandemic.

Pharmacovigilance practices in South Asian Association for Regional Cooperation countries: the need for collaboration

Objectives: One-fifth of the world's population lives in eight countries that constitute the South Asian Association for Regional Cooperation (SAARC). There is very little coordination among SAARC countries regarding the harmonization of pharmaceutical regulations and medicines safety. Pakistan, India and Bangladesh have experienced medicine-related tragedies where many patients have died. This study aims to examine current pharmacovigilance activity in the SAARC region to improve pharmacovigilance practices and to make recommendations for building a platform for collaboration to improve the safety monitoring of medicines in the region. The current review utilized secondary data. We reviewed the official websites of all SAARC countries' national regulatory authorities for pharmacovigilance-related information. A data set with eleven pharmacovigilance indicators were gathered and synthesized. Key Findings: All eight SAARC member countries have pharmacovigilance systems with full membership in the WHO Program for International Drug Monitoring. Out of eleven pharmacovigilance indicators, India met ten;Pakistan, Bangladesh and Bhutan nine;Maldives and Afghanistan seven;Nepal and Sri Lanka five. The SAARC countries do not have a harmonized pharmacovigilance system or centralized database. Due to positioning in different WHO regions, it is proposed to create a consortium on medicine safety among SAARC countries like other regional organizations of the world to strengthen the pharmacovigilance systems and harmonize the pharmacovigilance practices among member countries. Summary: To improve the quality of medicines and to strengthen regional medicine safety, the SAARC secretariat should consider forming a technical group of all member countries' regulatory authorities.Copyright © 2022 The Author(s). Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved.

Bike Sharing and Health

Civil Aviation is a vital sector of the global economy. The US National Airspace System (NAS) provides a network of airspace, air navigation facilities, equipment, services, airports, technical information, and personnel needed for the operation of civil aviation in the United States. The capacity of the airspace in the current system is primarily limited by the ability of the air traffic controllers to maintain situational awareness and provide separation services to the aircraft. Currently, there is an unprecedented decline of between 56% and 60% in air traffic demand due to the outbreak of corona virus (COVID-19) pandemic in China and its rapid spread to the rest of the world. Before the pandemic, the 2020 FAA forecast predicted the air traffic demand to grow over the next 20 years with an annual growth rate of about 2%. This anticipated increase in traffic will put a further strain on the airports and the airspace;it will result in large delays, airline schedule breakdown, and adverse environmental impact. The system needs to address developments and anticipated explosive growth in low speed and low-cost urban air mobility vehicles. This article provides an overview of Air Traffic Management (ATM) in the United States, brief review of current aviation operations, research under development, and technology and infrastructure upgrades currently being deployed to enable the current aviation system to meet the needs of future aviation systems. Air traffic operations need to be harmonized across all parts of the globe to achieve standardization and efficiency of operations. © 2021 Elsevier Ltd. All rights reserved

The DataHarmonizer: a tool for faster data harmonization, validation, aggregation and analysis of pathogen genomics contextual information.

Pathogen genomics is a critical tool for public health surveillance, infection control, outbreak investigations as well as research. In order to make use of pathogen genomics data, they must be interpreted using contextual data (metadata). Contextual data include sample metadata, laboratory methods, patient demographics, clinical outcomes and epidemiological information. However, the variability in how contextual information is captured by different authorities and how it is encoded in different databases poses challenges for data interpretation, integration and their use/re-use. The DataHarmonizer is a template-driven spreadsheet application for harmonizing, validating and transforming genomics contextual data into submission-ready formats for public or private repositories. The tool's web browser-based JavaScript environment enables validation and its offline functionality and local installation increases data security. The DataHarmonizer was developed to address the data sharing needs that arose during the COVID-19 pandemic, and was used by members of the Canadian COVID Genomics Network (CanCOGeN) to harmonize SARS-CoV-2 contextual data for national surveillance and for public repository submission. In order to support coordination of international surveillance efforts, we have partnered with the Public Health Alliance for Genomic Epidemiology to also provide a template conforming to its SARS-CoV-2 contextual data specification for use worldwide. Templates are also being developed for One Health and foodborne pathogens. Overall, the DataHarmonizer tool improves the effectiveness and fidelity of contextual data capture as well as its subsequent usability. Harmonization of contextual information across authorities, platforms and systems globally improves interoperability and reusability of data for concerted public health and research initiatives to fight the current pandemic and future public health emergencies. While initially developed for the COVID-19 pandemic, its expansion to other data management applications and pathogens is already underway.

Three rounds of a national external quality assessment reveal a link between disharmonic anti-SARS-CoV-2 antibody quantifications and the infection stage.

OBJECTIVES: The WHO's standardized measuring unit, "binding antibody units per milliliter (BAU/mL)," should allow the harmonization of quantitative results by different commercial Anti-SARS-CoV-2 immunoassays. However, multiple studies demonstrate inter-assay discrepancies. The antigenic changes of the Omicron variant affect the performance of Spike-specific immunoassays. This study evaluated the variation of quantitative Anti-SARS-CoV-2-Spike antibody measurements among 46, 50, and 44 laboratories in three rounds of a national external quality assessment (EQA) prior to and after the emergence of the Omicron variant in a diagnostic near-to-real-life setting. METHODS: We analyzed results reported by the EQA participant laboratories from single and sequential samples from SARS-CoV-2 convalescent, acutely infected, and vaccinated individuals, including samples obtained after primary and breakthrough infections with the Omicron variant. RESULTS: The three immunoassays most commonly used by the participants displayed a low intra-assay and inter-laboratory variation with excellent reproducibility using identical samples sent to the participants in duplicates. In contrast, the inter-assay variation was very high with all samples. Notably, the ratios of BAU/mL levels quantified by different immunoassays were not equal among all samples but differed between vaccination, past, and acute infection, including primary infection with the Omicron variant. The antibody kinetics measured in vaccinated individuals strongly depended on the applied immunoassay. CONCLUSIONS: Measured BAU/mL levels are only inter-changeable among different laboratories when the same assay was used for their assessment. Highly variable ratios of BAU/mL quantifications among different immunoassays and infection stages argue against the usage of universal inter-assay conversion factors.

Standardization of SARS-CoV-2 Cycle Threshold Values: Multisite Investigation Evaluating Viral Quantitation across Multiple Commercial COVID-19 Detection Platforms.

The demand for testing during the coronavirus disease 2019 (COVID-19) pandemic has resulted in the production of several different commercial platforms and laboratory-developed assays for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This has created several challenges, including, but not limited to, the standardization of diagnostic testing, utilization of cycle threshold (CT) values for quantitation and clinical interpretation, and data harmonization. Using reference standards consisting of a linear range of SARS-CoV-2 concentrations quantitated by viral culture-based methods and droplet digital PCR, we investigated the commutability and standardization of SARS-CoV-2 quantitation across different laboratories in the United States. We assessed SARS-CoV-2 CT values generated on multiple reverse transcription-PCR (RT-PCR) platforms and analyzed PCR efficiencies, linearity, gene targets, and CT value agreement. Our results demonstrate the inappropriateness of using SARS-CoV-2 CT values without established standards for viral quantitation. Further, we emphasize the importance of using reference standards and controls validated to independent assays, to compare results across different testing platforms and move toward better harmonization of COVID-19 quantitative test results. IMPORTANCE From the onset of the COVID-19 pandemic, the demand for SARS-CoV-2 testing has resulted in an explosion of analytical tests with very different approaches and designs. The variability in testing modalities, compounded by the lack of available commercial reference materials for standardization early in the pandemic, has led to several challenges regarding data harmonization for viral quantitation. In this study, we assessed multiple commercially available RT-PCR platforms across different laboratories within the United States using standardized reference materials characterized by viral culture methods and droplet digital PCR. We observed variability in the results generated by different instruments and laboratories, further emphasizing the importance of utilizing validated reference standards for quantitation, to better harmonize SARS-CoV-2 test results.

Converting to an international unit system improves harmonization of results for SARS-CoV-2 quantification: Results from multiple external quality assessments.

BACKGROUND: The detection of SARS-CoV-2 vRNA in clinical samples has relied almost exclusively on RT-qPCR as the gold standard test. Published results from various external quality assessments ("ring trials") worldwide have shown that there is still a large variability in results reported for the same samples. As reference standards of SARS-CoV-2 RNA are available, we tested whether using standard curves to convert Ct values into copies/mL (cp/mL) improved harmonization. METHODS: Nine laboratories using 23 test systems (15 of which were unique) prepared standard dilution curves to convert Ct values of 13 SARS-CoV-2 positive samples to cp/mL (hereafter IU/mL). The samples were provided in three rounds of a virus genome detection external quality assessment (EQA) scheme. We tested the precision and accuracy of results reported in IU/mL, and attempted to identify the sources of variability. RESULTS: Reporting results as IU/mL improved the precision of the estimated concentrations of all samples compared to reporting Ct values, although some inaccuracy remained. Variance analysis showed that nearly all variability in data was explained by individual test systems within individual laboratories. When controlling for this effect, there was no significant difference between all other factors tested (test systems, EQA rounds, sample material). CONCLUSIONS: Converting results to copies/mL improved precision across laboratory test systems. However, it seems the results are still very specific to test systems within laboratories. Further efforts could be made to improve accuracy and achieve full harmonization across diagnostic laboratories.

New development: The development of standardized charts of accounts in public sector accounting

IMPACTCharts of Accounts (CoAs) in the public sector are important to control accounting records. They support the preparation of accurate and reliable financial statements and consolidated reporting. Standardized CoAs at the national level are desirable but specificities of different public sector areas must be considered, as well as harmonization with budget and Government Finance Statistics (GFS) classifications. Having broad international guidance for each country to develop its own CoA, while fostering public sector financial reporting harmonization, would allow for improved comparability of fiscal effects during difficult periods, such as the Covid 19 pandemic.This article addresses the development of standardized Charts of Accounts (CoAs) in public sector accounting and reporting. In particular, it focuses on matters concerning the role CoAs have, or should have, at a national level, their main technicalities and the expected impact of using them as a bookkeeping instrument on the accuracy of accounting records and, ultimately, on the reliability and usability of the financial information for different purposes. Empirical evidence is provided from a survey to representatives of accounting international and national (Belgium, Brazil, Estonia and Portugal) standard-setters and preparers.

EU Public Procurement Policy During Covid-19: A Turning Point for Legitimate EU Governance?

Public procurement is a policy area located between two contradictory tendencies. On the one hand, the European Commission strives for greater competition to widen procurement markets. On the other hand, the boosting of competition encounters resistance among the member states. This article investigates how these colliding tendencies played out during the initial stages of the Covid-19 crisis and, more specifically, how changes in the field of procurement affected legitimate governance in the EU. Based on institutionalist and EU governance theories, the study contributes to the literature with three principal findings. First, it demonstrates that the pandemic enabled exogenously driven changes in the field of public procurement with new policies and guidelines, while the EU’s overall aims in this field were upheld. Second, the study demonstrates that the Commission was the main driver of change and that it enhanced the harmonisation of procurement rules and supranational integration despite the crisis. Third, while these changes strengthened the role of supranational actors, the study demonstrates that the changes introduced allow member states increased flexibility when it comes to the implementation. In practice, however, this flexibility has the potential to undermine the EU’s initial aims, thereby jeopardising the EU’s legitimacy.

Issues With Variability in Electronic Health Record Data About Race and Ethnicity: Descriptive Analysis of the National COVID Cohort Collaborative Data Enclave.

BACKGROUND: The adverse impact of COVID-19 on marginalized and under-resourced communities of color has highlighted the need for accurate, comprehensive race and ethnicity data. However, a significant technical challenge related to integrating race and ethnicity data in large, consolidated databases is the lack of consistency in how data about race and ethnicity are collected and structured by health care organizations. OBJECTIVE: This study aims to evaluate and describe variations in how health care systems collect and report information about the race and ethnicity of their patients and to assess how well these data are integrated when aggregated into a large clinical database. METHODS: At the time of our analysis, the National COVID Cohort Collaborative (N3C) Data Enclave contained records from 6.5 million patients contributed by 56 health care institutions. We quantified the variability in the harmonized race and ethnicity data in the N3C Data Enclave by analyzing the conformance to health care standards for such data. We conducted a descriptive analysis by comparing the harmonized data available for research purposes in the database to the original source data contributed by health care institutions. To make the comparison, we tabulated the original source codes, enumerating how many patients had been reported with each encoded value and how many distinct ways each category was reported. The nonconforming data were also cross tabulated by 3 factors: patient ethnicity, the number of data partners using each code, and which data models utilized those particular encodings. For the nonconforming data, we used an inductive approach to sort the source encodings into categories. For example, values such as "Declined" were grouped with "Refused," and "Multiple Race" was grouped with "Two or more races" and "Multiracial." RESULTS: "No matching concept" was the second largest harmonized concept used by the N3C to describe the race of patients in their database. In addition, 20.7% of the race data did not conform to the standard; the largest category was data that were missing. Hispanic or Latino patients were overrepresented in the nonconforming racial data, and data from American Indian or Alaska Native patients were obscured. Although only a small proportion of the source data had not been mapped to the correct concepts (0.6%), Black or African American and Hispanic/Latino patients were overrepresented in this category. CONCLUSIONS: Differences in how race and ethnicity data are conceptualized and encoded by health care institutions can affect the quality of the data in aggregated clinical databases. The impact of data quality issues in the N3C Data Enclave was not equal across all races and ethnicities, which has the potential to introduce bias in analyses and conclusions drawn from these data. Transparency about how data have been transformed can help users make accurate analyses and inferences and eventually better guide clinical care and public policy.

Harmonization of Multiple SARS-CoV-2 Reference Materials Using the WHO IS (NIBSC 20/136): Results and Implications.

Background: There is an urgent need for harmonization between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology platforms and assays prior to defining appropriate correlates of protection and as well inform the development of new rapid diagnostic tests that can be used for serosurveillance as new variants of concern (VOC) emerge. We compared multiple SARS-CoV-2 serology reference materials to the WHO International Standard (WHO IS) to determine their utility as secondary standards, using an international network of laboratories with high-throughput quantitative serology assays. This enabled the comparison of quantitative results between multiple serology platforms. Methods: Between April and December 2020, 13 well-characterized and validated SARS-CoV-2 serology reference materials were recruited from six different providers to qualify as secondary standards to the WHO IS. All the samples were tested in parallel with the National Institute for Biological Standards and Control (NIBSC) 20/136 and parallel-line assays were used to calculate the relevant potency and binding antibody units. Results: All the samples saw varying levels of concordance between diagnostic methods at specific antigen-antibody combinations. Seven of the 12 candidate materials had high concordance for the spike-immunoglobulin G (IgG) analyte [percent coefficient of variation (%CV) between 5 and 44%]. Conclusion: Despite some concordance between laboratories, qualification of secondary materials to the WHO IS using arbitrary international units or binding antibody units per milliliter (BAU/ml) does not provide any benefit to the reference materials overall, due to the lack of consistent agreeable international unit (IU) or BAU/ml conversions between laboratories. Secondary standards should be qualified to well-characterized reference materials, such as the WHO IS, using serology assays that are similar to the ones used for the original characterization of the WHO IS.