UK MHRA's Guidance: Use of Real-World Data in Clinical Studies for Regulatory Decisions

The integration of real-world data (RWD) in clinical research is revolutionizing the pharmaceutical landscape. The Medicines and Healthcare products Regulatory Agency (MHRA) has released comprehensive guidance on utilizing RWD to support regulatory decisions, emphasizing its potential to enrich clinical studies and ultimately enhance healthcare outcomes.

Real-World Data

RWD refers to data collected outside traditional clinical trials, derived from sources such as electronic health records, insurance claims, and patient registries. The MHRA recognizes its value in providing broader evidence on treatment effects in real-world settings, potentially offering insights that controlled clinical trial environments may not capture.

Guidance Structure and Updates

MHRA guidance on the use of real-world data in clinical studies to support regulatory decisions

The MHRA guidance, last updated on 20 May 2025, is a comprehensive framework outlining methodologies for integrating RWD into clinical studies. This guidance is essential for industry stakeholders looking to leverage real-world evidence alongside traditional clinical trial data to support regulatory submissions.

• Data Quality and Validity: The guidance lays out stringent criteria for data quality, emphasizing that RWD must be robust, reliable, and relevant. It includes standards for ensuring that the data accurately reflect real-world patient experiences and outcomes. The focus is on reducing biases and ensuring the data's statistical validity to make it suitable for regulatory use.

• Appropriate Contexts for RWD Applications: The guidance provides context-specific recommendations on where RWD can be most effectively applied. It encourages its use in post-market surveillance and for providing supplementary evidence in submissions where clinical trial data alone may not suffice.

MHRA draft guideline on the use of external control arms based on real-world data to support regulatory decisions

The draft guideline is currently open for consultation and focuses on the novel use of RWD to create external control arms in clinical studies. This approach is particularly valuable for conditions where traditional randomized control groups are not feasible or ethical.

• External Control Arms: These are comparator groups sourced from existing real-world data rather than randomized clinical trials. This methodology can provide comparative effectiveness information, especially in areas such as rare diseases, where patient recruitment for control groups can be challenging.

The open consultation allows stakeholders to provide feedback and insights to refine these guidelines, fostering a collaborative regulatory environment.

Regulatory Considerations

The guidance outlines critical regulatory considerations when employing RWD:

• Data Integrity and Relevance: The MHRA stresses the importance of maintaining data integrity and ensuring relevance to the clinical question at hand. This involves rigorous validation and cleaning processes to ensure the reliability of the data used in analyses.

• Transparency and Methodological Rigor: Regulatory expectations include transparent reporting of methodologies and adherence to rigorous analytical standards. This ensures that RWD can be a credible component of regulatory decision-making processes, supporting claims regarding safety and efficacy.

Overall, the guidance fosters the use of RWD under structured methodologies, emphasizing its potential to supplement traditional data and enrich the evidentiary landscape in clinical research.

These updates reflect the MHRA's commitment to embracing innovative approaches to drug development and regulation, aligning with global trends and promoting the effective integration of RWD in healthcare decisions.ata-driven evidence in their clinical and regulatory endeavours.