Real-world evidence (RWE) is becoming foundational in how health technology assessment (HTA) agencies evaluate therapeutic value under real-world conditions. But integrating RWE into decision-making raises critical questions: What makes it robust? How should it be tested and evaluated? And what infrastructure ensures consistent, scalable use?
Earlier this month, I joined HTA leaders, researchers, and policymakers at the SUSTAIN-HTA Advisory Group meeting in Budapest. The initiative, funded by the European Commission, is designed to help agencies integrate existing and emerging methods into their procedures and processes. SUSTAIN-HTA is organized around four core workstreams: identifying methodological gaps across agencies, fostering collaboration between HTA bodies and academic institutions, supporting training and capacity-building, and establishing a sandbox environment for testing methods in applied settings.
While SUSTAIN-HTA is focused on HTA methods and processes in general, Aetion has been involved in similar activities that focus specifically on developing methods, processes, and workforce capabilities to integrate RWE in HTA decision-making:
- Creating sandbox environments to test and validate RWE methods before broad adoption.
- Building institutional capability through workforce training and cross-agency coordination.
Sandbox testing as a foundation for real-world evidence in HTA
SUSTAIN-HTA’s sandbox model gives agencies a structured space to evaluate new methods in practice. Aetion®’s real-world collaborations reflect this approach, demonstrating how methodologically sound RWE can reduce uncertainty and improve HTA decision-making.
In collaboration with the National Institute for Health and Care Excellence (NICE), Aetion led a comparative effectiveness study of apixaban versus rivaroxaban for atrial fibrillation, using UK general practice data. The project addressed a critical evidence gap: the absence of head-to-head randomized controlled trial data comparing direct oral anticoagulants. It also allowed NICE to test advanced methodologies—including STaRT-RWE and target trial emulation—in a real-world setting, contributing to developing its broader real-world evidence framework.
We’ve also applied this model with the Institute for Clinical and Economic Review (ICER). In hereditary angioedema, real-world claims data were used to reexamine assumptions around attack frequency and dosing, materially influencing cost-effectiveness estimates. In sickle cell disease, RWE added critical context around treatment delivery in underserved populations and complex care environments.
Aetion has also developed methodological frameworks—such as the Structured Process to Identify Fit-For-Purpose Data (SPIFD) and the Structured Pre- and Post-Approval Comparative Study Design Framework to Generate Valid and Transparent Real-World Evidence for Regulatory Decisions (SPACE)—to guide structured study planning, external validity assessment, and fit-for-purpose evaluation. These are increasingly used in HTA settings to support reproducibility and transparency.
These efforts show that sandbox testing is not theoretical—it works. When agencies can test methods through applied projects, they gain operational confidence and clearer pathways for integration.
Method testing is essential, but implementation is the harder task
While sandbox projects are vital for methodological development, their long-term impact depends on internal capability. Sustained integration of newly developed or existing methods—including real-world evidence in HTA—requires teams trained to assess methodological fit, apply protocols appropriately, and interpret results within a decision-grade framework.
This need is global. HTA bodies in the EU and payers in the U.S. are investing in workforce development to improve decision-making. For example, AMCP is leading efforts to educate the U.S. payer workforce on how and when to use RWE in formulary and coverage decisions, with Aetion contributing to those initiatives. Similarly, SUSTAIN-HTA supports agency staff in building broader methodological literacy across all HTA domains.
Collectively, these investments reflect a shared priority: equipping evaluators with the tools and training needed to apply best practices and ensure RWE is used consistently, appropriately, and confidently.
Method maturity comes through use—not just guidance
Publishing RWE frameworks is essential, but adoption depends on whether those frameworks are paired with operational methods that can be tested, refined, and scaled. Method maturity comes not from position papers, but from real use—through replication, demonstration, and iterative learning in policy settings.
That process is already underway. As more HTA agencies institutionalize RWE into their assessments, regulatory alignment, methodological standards, and operational readiness will define the next adoption phase.
Aetion Supports the Infrastructure for RWE at Scale
As HTA agencies move from interest in RWE to structured, routine use, Aetion® provides the infrastructure to support that shift, combining validated frameworks, transparent analytics, and real-world implementation experience with organizations like NICE and ICER.
Whether through sandbox testing, workforce training, or method development, Aetion is helping agencies build the readiness to apply RWE consistently across therapeutic and policy contexts.
Schedule a consultation with our team to learn how Aetion Evidence Platform®, our data partnerships, and our scientific services support applied RWE in HTA.