Advancing real-world evidence harmonization: lessons from the UK, EMA and global policy frameworks

Area of Science:

• Health policy
• Regulatory science
• Health technology assessment

Background:

• Real-world evidence (RWE), derived from real-world data (RWD), is crucial for regulatory and health technology assessment (HTA) decisions.
• Existing RWE policy frameworks are inconsistent across jurisdictions due to varying applications (safety, effectiveness, health economics).
• This fragmentation can lead to inefficiencies and delays in patient access to new therapies.

Purpose of the Study:

• To compare RWE guidance from twelve major regulatory and HTA agencies.
• To analyze frameworks across data quality, statistical methods, registry governance, and transparency.
• To identify opportunities for harmonization in RWE generation and evaluation.

Main Methods:

• A narrative comparative policy review of RWE guidance documents.
• Analysis of frameworks from agencies including MHRA, EMA, FDA, and CADTH.
• Comparison across four key domains: data quality, statistical methods, governance, and transparency.

Main Results:

• High-level principles for RWE show convergence, but operational expectations diverge significantly.
• Agencies like MHRA, EMA, and FDA have distinct approaches (flexibility vs. consistency vs. comprehensive guidance).
• HTA bodies add criteria for comparative effectiveness and value, further fragmenting RWE use.

Conclusions:

• RWE fragmentation stems from both functional differences and operational misalignment.
• Harmonization necessitates shared minimum standards and transparency, not just more guidelines.
• Collaborative pilots, particularly leveraging the UK's post-Brexit position, can support pragmatic alignment.