Combining Real-World and Clinical Trial Data Through Privacy-Preserving Record Linkage: Opportunities and Challenges—A Narrative Review

Abstract

Background and Aims

Despite their widespread use, randomized clinical trials (RCTs) face challenges like differential loss to follow-up, which can impact validity. Real-world evidence (RWE) from real-world data (RWD) is increasingly used to address these limitations, but RCTs and RWE have provided complementary, disconnected observations of the patient journey. Privacy-preserving record linkage (PPRL) enables the integration of patient records across these data sources. This narrative review explores the potential use cases of PPRL to overcome the limitations of both RCTs and RWD for clinical research and regulatory decision-making.

Methods

This manuscript is a narrative review and did not involve the collection or analysis of primary research data. The authors aimed for comprehensive topic coverage and a synthesis of key concepts from the current literature, rather than adhering to a formal systematic review protocol (e.g., PRISMA).

Results

PPRL can generate a more comprehensive understanding of patient interaction with the healthcare system. For example, long-term information about participants before and after a trial can assist in identifying predictors of drug response or intolerance, reducing patient burden, and providing alternatives to traditional study designs. Linked data applications include expanding patient health histories and creating comprehensive patient data repositories that enable innovative trial designs. However, opportunities remain to demonstrate the provenance, quality, and completeness of RWD sources to ensure scientific rigor.

Conclusion

Combining RCTs and RWD through PPRL offers significant and insufficiently explored potential for advancing drug development research, reducing operational costs, and enhancing data availability. Further consideration of PPRL use cases may drive innovative trial designs augmented with RWD, improving the ability of this collected data to support informed decision-making.