(161) Linking clinical trial participants to their U.S. real-world data through tokenization: a practical guide

Background: The use of real-world data (RWD) has augmented our understanding of patients’ health care experiences and the effects of treatments beyond clinical trials. Although electronic health record (EHR) data integration at clinical trial sites is a widely adopted practice, primarily for recruitment and data capture, a challenge to data utility is the fragmentation of health data across different sources. Linking RWD sources to each other and to trial data -- while preserving patient privacy through tokenization -- aids in filling evidence gaps with outcome data and facilitates the generalization of effects from controlled trial environments to real-world settings.

Objectives: 1. Describe the applications of RWD linkage and how they benefit both clinical development and real-world decision-making.
2. Address the operational aspects of linking trial data to RWD, emphasizing the importance of using privacy-preserving record linking systems with established metrics of accuracy and precision, managing consent, and providing the necessary training and resources at trial sites to inform participants about providing access to their RWD through data linkage.

Methods: A review of the purposes of trial-RWD linkage and best practices for operationalizing linkage was done.

Results: Trial benefits include improving interpretability and generalizability (e.g., by remediating missing data or losses to follow-up), enabling validation of RWD variables against trial measures, extending follow-up beyond trial closeout, and characterizing the applicability of trial results to under-represented groups.
Operationalization occurs in four steps: 1) select a privacy-preserving record linking system (PPRLS) that can be used with most -- if not all -- RWD sources of interest; 2) develop consent processes; 3) enable sites to consent patients to tokenization and to collect and manage personally identifiable information (PII); and 4) identify fit-for-purpose RWD for linkage.

Conclusions: Integrating fragmented health data can result in a more complete representation of the patient's experience than any one RWD source or clinical trial can offer on its own. Linkage across RWD sources or between RWD and trial data can confer gains in scientific understanding, as well as improving recruitment efficiency and data quality. Technologic advances in PPRLS and benchmarking have improved linkage accuracy, although record and variable validation studies remain an essential component of reliable evidence generation. For trial-RWD linkage, patient consent and linkage operational hurdles are surmountable with appropriate planning and supporting materials for sites to inform study participants.