As Rare Communities Drive Real-World Evidence (RWE) Innovation, Are They Carrying Its Burden?
In the last five years, RWE has become more widely accepted by payers to address data gaps for rare disease indications, and it is particularly crucial when an RCT is not feasible and/or would be unethical to conduct. Moreover, RWE can provide unique insights into natural history and patient experiences when these data are unattainable through conventional methods (e.g. when a prospective natural history study is no longer feasible due to widespread treatment uptake). However, challenges must still be overcome to ensure robust RWE can be obtained from different settings. Considering the unique features of individual health data systems across Europe, stakeholders need to be cautious about the validity of findings derived from amalgamated datasets. There is therefore an urgent need for standardised methodologies and stronger collaboration across Europe to harmonise RWE practices. While ongoing pilot studies, such as DARWIN EU’s natural history study in rare blood cancers,6 may promote consensus among HTA bodies on the use of RWE, manufacturers will need to strategise and engage early to ensure RWE data sources are relevant and useful.
European Reference Networks (ERNs) have helped to generate robust RWE for rare disease management and research, as highlighted at the World Orphan Drug Congress 2023. ERNs, connecting over 1600 healthcare units and 400 hospitals,7 form a unique component of the European healthcare ecosystem. By addressing regional governance and institutional barriers, ERNs position Europe as a leader in real-world data collection for rare diseases. The conference spotlighted the Together for Rare Diseases (Together4RD) initiative, targeting tangible and perceived barriers to ERN-industry collaboration, for example by consolidating good practices from disease-related pilots to demonstrate how ERNs can work with industry.8 Graham Slater of EURORDIS described this opportunity to advance ERN research as significant, given the >30 million people in the EU living with a rare disease.9
The increasing development of advanced therapy medicinal products, with claims of long-term (or lifelong) effectiveness, leads to a growing need for RWE to demonstrate sufficient clinical value to justify high one-off treatment costs. With smaller populations requiring fewer resources to support this evidence generation, RWE efforts often centre in the rare disease space. This threatens rare disease communities with the increased burden of supporting RWE innovation, particularly given that rare conditions are often complex and heterogeneous. This creates the risk that already underserved rare disease communities bear the brunt of failed experimentation or substandard methods for RWE analysis; it is therefore critical that the HEOR community as a whole works to further best practices for use of RWE, to ensure its application in the rare disease setting is appropriate and fully realises its potential to benefit these patients.