Leveraging a global, rederated, real-world data network to optimize investigator-initiated pediatric clinical trials: The TriNetX Pediatric Collaboratory Network

Clinical research networks facilitate collaborative research, but data-sharing remains a common barrier. The**** TriNetX platform provides real-time access to electronic health record-derived, anonymized data from 173 healthcare organizations (HCOs) and tools for queries and analysis. In 2022, four pediatric HCOs worked with TriNetX leadership to found the Pediatric Collaboratory Network (PCN), facilitated via a multi-institutional data use agreement (DUA). The DUA enables collaborative study design and execution, with institutional review board (IRB)-approved transfer of complete datasets for further analyses on a per-protocol basis. Of the 41.2 million children with TriNetX records, the PCN represents nearly 10%. The PCN assisted several early-career investigators in bringing study concepts from conception to an international scientific meeting presentation and journal submission. The PCN facilitates EHR vendor-agnostic multicenter pediatric research on the global TriNetX platform. Continued growth of the PCN will advance knowledge in pediatric health.

Methods
TriNetX platform: The TriNetX platform is a global, federated network where users can access continuously updated, anonymized electronic health records (EHR) data, including demographics, encounters, diagnoses, procedures, medications, laboratory values, vitals, and genomics. TriNetX provides sites with mapping to their common data model, which reduces onboarding burden. Compared to other popular data models such as i2b2 or OMOP, HCOs with limited IT and data resources benefit from the data harmonization and TriNetX’s EHR-agnostic infrastructure, which allows secure access to information shared from their data warehouses and EHRs. The TriNetX platform includes self-service tools that allow patient data to be aggregated and queried based on the inclusion/exclusion criteria for a given research project. Users can perform cohort comparison and analysis across clinical profiles and longitudinal measures. Publications drawing on TriNetX have demonstrated utility in answering research questions and gaining access to representative cohorts across diverse care settings.

PCN framework and infrastructure: The PCN, founded in 2022, permits federated pediatric queries across sites in TriNetX to facilitate collaboration between investigators and subject-matter experts with similar interests. As active contributors to the network, each PCN member applies a data-driven approach to their work, repurposing EHR data for clinical investigation. Although aggregated data from member sites is visible in the TriNetX Global Health Research Network, the “added value” of the PCN master data-use agreement (DUA) is to improve collaborations by making it simpler for investigators to meet experts at other PCN member sites. The PCN is visible in the global TriNetX portal as a selectable network, and results are returned immediately with patient counts and abundant clinical data for each participating site (Figure 2; Table 1). A key feature is that no additional IRB reviews are needed to participate in or query the PCN. However, if a specific collaboration requires the collection and sharing of additional data not already provided to TriNetX, IRB approval or a letter of exemption is necessary. A steering committee of institutionally designated representatives, including biostatistics experts, from the four core sites and two TriNetX representatives, meets monthly to discuss data governance, coordination efforts, and new site engagement. To mitigate barriers to entry, the steering committee designed the membership process to be inclusive while ensuring that the structure and underlying mission of the PCN are maintained. Steering committee members can invite junior faculty to present research concepts and ongoing work that could benefit from PCN participation and PCN-based analyses. Investigators working under the master DUA can obtain aggregated counts at each of the PCN sites and ask the established point of contact at PCN sites for introductions to potential collaborators or learn how to share additional information unavailable through TriNetX. This might include, subject to IRB approval, obtaining de-identified data or validation of data at participating sites.

RESULTS

By relying on the Common Data Model provided by TriNetX, PCN members can focus their efforts on data exploration and collaboration. One clear advantage is that early-career investigators can design and execute single-center and multicenter data queries and out-of-the-box analytics in support of their research aims with little to no investment (e.g., research funding, personnel) [Figure 3]. While members of the TriNetX Global Health Research Network can execute queries across the entire network, the community created by the PCN—which shares a common interest in pediatric research to learn from each other’s experiences and recommendations—may be of greatest utility. The PCN provides a consultative forum in which junior investigators can optimize the design of their queries and analytic approaches, as well as obtain guidance in preparing IRB protocols where warranted.