The Future of Real-World Evidence: Insights from Shirley Wang's Keynote at the Health Data Forum Global Hybrid Summit 2024

Shirley Wang's keynote presentation offered a fascinating exploration of the ongoing efforts to bridge the gap between real-world evidence (RWE) and randomized clinical trials (RCTs). Her talk highlighted the groundbreaking RCT Duplicate Project, which focuses on using real-world data (RWD) to emulate clinical trials, uncover lessons, and address challenges in this emerging field.

Lessons from the RCT Duplicate Project

Over five years, the RCT Duplicate Project has emulated more than 30 trials, aiming to validate RWE studies by comparing their results to completed trials. Wang underscored the dual goals of improving the credibility of RWE and addressing scepticism about its ability to generate causal inferences. Key lessons included:

1. The Role of Trial Design Emulation: Accurate RWE emulations require meticulous attention to trial design. Divergences in results often stem from design differences rather than inherent bias in RWE.
2. Placebo Control Challenges: Emulating placebo-controlled trials proved particularly difficult. Active comparators often introduced confounding variables, as seen in trials involving diabetes medications.
3. Time-Dependent Effects and Adherence: Trials with delayed or time-varying effects—such as osteoporosis treatments—posed unique challenges, especially when real-world adherence was low.

Expanding the Boundaries of Real-World Data

Wang also shared updates on the project’s ongoing initiatives, which include:

• Oncology Trials: The team is now working to emulate 12 oncology trials using speciality electronic health record (EHR) data.
• Pediatric Trials: Addressing the unique challenges of RWE in children, where irregular healthcare visits complicate confounding adjustments.
• Predicting Trial Outcomes: Efforts to predict outcomes for trials that were ongoing when protocols were registered are yielding promising insights.
• Methodological Innovations: Developing tools like the "Benchmark Expand Calibrate" methodology to refine emulations and guide expansion to supplemental indications.

The Impact of RWE on Healthcare

One of the most significant takeaways from Wang’s presentation was the growing acceptance of RWE as a complement—not a replacement—to RCTs. The work done by Wang's team has already influenced regulatory bodies and health technology assessment agencies worldwide. For instance, the Harper Protocol Template has been endorsed as a standardized approach to enhance reproducibility in RWE studies.

The implications of this work extend far beyond academia. Governments and policymakers stand to benefit from the integration of RWE into decision-making processes, enabling more efficient allocation of resources and improved healthcare outcomes for millions.

The Role of AI in the Future of RWE

When asked about the role of AI in advancing RWE, Wang highlighted its potential in areas like phenotype identification and natural language processing for data extraction. However, she cautioned that validation studies remain essential to ensure AI-generated insights are reliable and meaningful.

Conclusion

Wang's keynote was a compelling reminder of the transformative potential of RWE when conducted rigorously and transparently. By addressing the challenges of design emulation, leveraging new methodologies, and integrating cutting-edge technologies like AI, the field is poised to revolutionize healthcare decision-making.

As RWE continues to gain credibility, initiatives like the RCT Duplicate Project will serve as critical benchmarks, shaping a future where clinical trials and real-world evidence work hand in hand to improve patient care and outcomes.

Watch the presentation