Standardization of clinical trials subject ID schematics: A portfolio-wide model to enhance data integrity and regulatory compliance

Background: Subject identification is a cornerstone of data integrity and regulatory compliance in clinical trials. Legacy, study-specific subject ID conventions may cause risk of duplication, hinder traceability of rescreened participants, and complicate regulatory submissions-particularly in large global portfolios where multiple trials for similar disease areas from the same sponsor are handled by the same site and the same PI. Regulatory guidance from the U.S. Food and Drug Administration (FDA Technical Conformance Guide), the Clinical Data Interchange Standards Consortium (CDISC SDTM), and ICH E6(R2) mandates unique subject traceability throughout a study's lifecycle. Aim: This paper introduces, validates, and evaluates a standardized subject-identification schema designed to eliminate risk of duplication, ensure traceable rescreening, and harmonize subject IDs across an organization's clinical portfolio while aligning with global regulatory requirements. Methods: A cross-functional Biogen team spanning Global Clinical Operations, Data Systems, IT, Clinical Supply, with inputs from external partners (CROs and IXRT vendors) designed a new schema (SSSS-PYZ-XXXA). The structure encodes site (SSSS), program (P), phase (Y), study sequence (Z), subject number (XXX), and screening attempt (A). Validation comprised retrospective pressure testing with historical data, pilot implementation in active trials, and benchmarking against CDISC SDTM and FDA TCG standards. Results: The standardized schema eliminated subject-ID overlap across parallel studies, enabled seamless rescreen tracking without creating multiple USUBJIDs, and proved compatible with EDC, CTMS, IXRT, and LIMS systems. As of 2025, the schema had been adopted in at least 59 new trials across multiple therapeutic areas, improving SDTM mapping and regulatory preparedness. Conclusion: A portfolio-wide standardized subject-ID schema provides a sustainable, scalable framework that strengthens data integrity, streamlines operations, and enhances regulatory compliance across clinical development programs.