OBJECTIVE: We discuss implications of potential ascertainment biases for studies examining diabetes risk following SARS-CoV-2 infection using electronic health records (EHRs). We quantitatively explore sensitivity of results to misclassification of COVID-19 status using data from the U.S.-based Diabetes in Children, Adolescents and Young Adults (DiCAYA) Network on children (≤17 years) and young adults (18-44 years). MATERIALS AND METHODS: In our retrospective case study from the DiCAYA Network, SARS-CoV-2 was identified using labs and diagnoses from June 1, 2020 to December 31, 2021. Patients were followed through December 31, 2022 for new diabetes diagnoses. Sites examined incident diabetes by COVID-19 status using Cox proportional hazards models. Results were pooled in meta-analyses. A bias analysis examined potential impact of COVID-19 misclassification scenarios on results, guided by hypotheses that sensitivity would be <50% and would be higher among those who developed diabetes. RESULTS: Prevalence of documented COVID-19 was low overall and variable across sites (children: 4.4%-7.7%, young adults: 6.2%-22.7%). Individuals with documented COVID-19 were at higher risk of incident diabetes compared to those with no documented infection, but results were heterogeneous across sites. Findings were highly sensitive to COVID-19 misclassification assumptions. Observed results could be biased away from the null under several differential misclassification scenarios. DISCUSSION: Although EHR-based documentation of COVID-19 was associated with incident diabetes, COVID-19 phenotypes likely had low sensitivity, with considerable variation across sites. Misclassification assumptions strongly impacted interpretation of results. CONCLUSION: Given the potential for low phenotype sensitivity and misclassification, caution is warranted when interpreting analyses of COVID-19 and incident diabetes using clinical or administrative databases.

OBJECTIVE: To construct a data quality (DQ) system that incorporates combinations of methods to evaluate data characteristics and analytic fitness across research questions for multiple uses. MATERIALS AND METHODS: Drawing from experience of other data quality programs, network data extraction needs, and recurring study requirements, we developed 5 standards to guide development of a modular, multifaceted data quality system. These included annotation and documentation, ability to measure research readiness, reproducibility across networks, flexibility for the user, and interpretability to research and project teams. Implementation of checks based on these principles focused on reusability and interactive visualization of results. RESULTS: We identified 10 check types producing over 444 check applications and deployed them in 2 multi-institutional networks. Check types span structural conformance to a data model, utility for common research needs, and study-specific customization. All check types are customizable without dependencies between them. A dashboard visualizes results, permitting adjustments based on number of data sources, need for source masking, and the user's focus. All components can be applied as written to any data source using OMOP and are readily modified for other data models. DISCUSSION: We have extended previous work through our novel and multifaceted approach to data quality assessment, addressing needs in both network data improvement and research usage. We developed a capable and deployable system rather than tailoring to specific use cases. CONCLUSION: Our novel DQ assessment system provides essential components for future standardization and collaboration to improve fitness of clinical data for intended use.

OBJECTIVE: This article describes the implementation of a privacy-preserving record linkage (PPRL) solution across PCORnet®, the National Patient-Centered Clinical Research Network. MATERIAL AND METHODS: Using a PPRL solution from Datavant, we quantified the degree of patient overlap across the network and report a de-duplicated analysis of the demographic and clinical characteristics of the PCORnet population. RESULTS: There were ∼170M patient records across the responding Network Partners, with ∼138M (81%) of those corresponding to a unique patient. 82.1% of patients were found in a single partner and 14.7% were in 2. The percentage overlap between Partners ranged between 0% and 80% with a median of 0%. Linking patients' electronic health records with claims increased disease prevalence in every clinical characteristic, ranging between 63% and 173%. DISCUSSION: The overlap between Partners was variable and depended on timeframe. However, patient data linkage changed the prevalence profile of the PCORnet patient population. CONCLUSIONS: This project was one of the largest linkage efforts of its kind and demonstrates the potential value of record linkage. Linkage between Partners may be most useful in cases where there is geographic proximity between Partners, an expectation that potential linkage Partners will be able to fill gaps in data, or a longer study timeframe.

We provide a generalizable framework for the systematic analysis of complicated, longitudinal clinical features in pediatric cancer. We use a threefold pipeline of exploratory data analysis, ontological categorization through a multi-modal data transformation process towards predictive analytics. We derive a data-driven phenotype from a subset of a sample of over 1900 brain tumor cases focused specifically on High-Grade Gliomas. We implement an analyst-friendly process to make machine learning-ready data sets based on domain ontologies ready for enumeration and vectorization. The results are clinical domain expert readable data points from 4.3 million observational events across 16,000 patient days. In this research, we address the gap in phenotypic data features by utilizing extensive harmonized observational clinical data and identify resources and specific processes for their use in rare tumor research.

Observational data resources based on the capture of clinical data in the electronic health record (EHR) have produced significant learning opportunities in many areas of medicine. These large data resources can span multiple hospital systems and employ common semantics, ontologies, and data models. They have uncovered critical safety issues for patients, and spurred observational research and clinical decision support. In the age of precision medicine there is also an increased need to obtain genomic and clinical data to discover novel treatments for the deadliest of diseases. With this, there are efforts to create deep-dive disease specific repositories that include tissue in biobanks. The latter require significant human annotation of biospecimens. Securing the data is especially critical in rare pediatric brain tumors. In the specific case of The Children's Brain Tumor Tissue Consortium (CBTTC) an international rare pediatric brain tumor repository, the number of patients that need to be followed prospectively is outpacing the ability of human annotation. In this preliminary study, we perform a prescribed data exploration analysis on simulation data in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) employed by the pediatric data network PEDSNet with the intention to ascertain feasibility in automatic annotation of patient records in the CBTTC.

OBJECTIVE: PEDSnet is a clinical data research network (CDRN) that aggregates electronic health record data from multiple children's hospitals to enable large-scale research. Assessing data quality to ensure suitability for conducting research is a key requirement in PEDSnet. This study presents a range of data quality issues identified over a period of 18 months and interprets them to evaluate the research capacity of PEDSnet. MATERIALS AND METHODS: Results were generated by a semiautomated data quality assessment workflow. Two investigators reviewed programmatic data quality issues and conducted discussions with the data partners' extract-transform-load analysts to determine the cause for each issue. RESULTS: The results include a longitudinal summary of 2182 data quality issues identified across 9 data submission cycles. The metadata from the most recent cycle includes annotations for 850 issues: most frequent types, including missing data (>300) and outliers (>100); most complex domains, including medications (>160) and lab measurements (>140); and primary causes, including source data characteristics (83%) and extract-transform-load errors (9%). DISCUSSION: The longitudinal findings demonstrate the network's evolution from identifying difficulties with aligning the data to a common data model to learning norms in clinical pediatrics and determining research capability. CONCLUSION: While data quality is recognized as a critical aspect in establishing and utilizing a CDRN, the findings from data quality assessments are largely unpublished. This paper presents a real-world account of studying and interpreting data quality findings in a pediatric CDRN, and the lessons learned could be used by other CDRNs.

A learning health system (LHS) integrates research done in routine care settings, structured data capture during every encounter, and quality improvement processes to rapidly implement advances in new knowledge, all with active and meaningful patient participation. While disease-specific pediatric LHSs have shown tremendous impact on improved clinical outcomes, a national digital architecture to rapidly implement LHSs across multiple pediatric conditions does not exist. PEDSnet is a clinical data research network that provides the infrastructure to support a national pediatric LHS. A consortium consisting of PEDSnet, which includes eight academic medical centers, two existing disease-specific pediatric networks, and two national data partners form the initial partners in the National Pediatric Learning Health System (NPLHS). PEDSnet is implementing a flexible dual data architecture that incorporates two widely used data models and national terminology standards to support multi-institutional data integration, cohort discovery, and advanced analytics that enable rapid learning.