UK MHRA Guidance: Use of Real-World Data in Clinical Studies to Support Regulatory Decisions (July 2025 Update)
- Sharan Murugan
- Jul 19
- 3 min read
In July 2025, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) released updated and expanded guidance on the use of real-world data (RWD) in clinical studies to support regulatory decisions. This update represents a significant milestone in the evolution of regulatory science, reflecting the growing importance of data generated outside traditional randomized controlled trials (RCTs).
What Is Real-World Data?
RWD refers to data relating to patient health status or healthcare delivery, collected outside traditional clinical studies. This includes:
Electronic health records (EHRs)
Primary and secondary care databases
Disease and patient registries
Administrative data (e.g., births and deaths)
Patient-reported outcomes (PROs)
Data from wearable devices and digital health technologies
Real-world evidence (RWE) is the information derived from the analysis of RWD and may inform regulatory decisions regarding efficacy and safety.
Why Use RWD?
Efficiency and Feasibility: Utilizing RWD can accelerate drug development and lower costs, making previously unfeasible studies possible.
Representativeness: RWD studies may provide more generalizable evidence of treatment effects in real-world settings.
Potential Applications: RWD is frequently used in post-marketing safety monitoring, and its use is expanding into supporting regulatory approvals, especially for label changes, new indications, or repurposing of licensed products.
MHRA Guidance Series Highlights
Applicability: The guidance applies to studies globally, not just those in the UK.
Data Quality: The data source must be of high quality—accurate, valid, reliable, and representative. Sponsors must assess:
Origin and processing of data
Linkage with other data sources
Interoperability challenges
Privacy regulations and security
Frequency and completeness of data capture
Validation: Any tools, methods, and technology (including digital health products) used to collect RWD must be validated for their specific use case1.
Oversight and Inspection: The MHRA conducts risk-based inspections to assess systems and data integrity, focusing on aspects such as randomization, data management, and safety reporting.
Scope: The guidance is tailored for prospective RCTs that use RWD as the principal data source (excluding purely observational studies or trials using RWD only as a control arm).
Value for Regulation: If the trial is well-designed and data quality robust, evidence from RCTs using RWD is considered as valuable as traditional RCTs in regulatory assessments.
Trial Categories: The guideline distinguishes trial types by risk:
Type A: No greater risk than routine care, often involving already licensed products or established off-label uses.
Type B/C: Increasing risk, such as new indications, higher dosages, or unlicensed products, with additional regulatory scrutiny.
Endpoints and Blinding: Objective endpoints (like mortality) routinely captured in EHRs are ideal for open-label, RWD-based RCTs. Blinding and hybrid designs may be required when endpoints are less objective or not systematically recorded.
Safety Monitoring: Legal requirements around adverse event reporting apply. A risk-adapted approach to safety monitoring is permitted, depending on prior knowledge of the product and the nature of data capture.
Feasibility Studies Recommended: Sponsors should perform preliminary assessments to ensure essential variables are well-captured in RWD sources.
The updated MHRA guidance marks an important step forward in modernizing clinical research and regulatory science. By outlining clear principles and pathways for using RWD and real-world RCTs, the agency offers industry and researchers a practical roadmap to harness the wealth of data generated in everyday healthcare.
This blog is based on the following updated MHRA guidance documents (July 2025):
Comments