Nonrandomized Real-World Evidence to Support Regulatory Decision Making: Process for a Randomized Trial Replication...

Area of Science:

• Health economics
• Biostatistics
• Regulatory science

Background:

• Recent legislation requires the US Food and Drug Administration (FDA) to provide guidance on using real-world evidence (RWE) for regulatory decisions.
• Concerns exist regarding the validity of nonrandomized RWE, particularly for assessing medication effectiveness, when compared to randomized controlled trials (RCTs).

Purpose of the Study:

• To assess the comparability of results from nonrandomized RWE, derived from healthcare claims data, with those from RCTs.
• To systematically evaluate the ability of nonrandomized RWE to replicate multiple RCTs.
• To provide insights into the strengths and limitations of using nonrandomized RWE from claims for regulatory decision-making.

Main Methods:

• An initiative was designed to compare nonrandomized RWE from healthcare claims data against existing RCTs.
• Forty RCTs were selected for this comparative analysis.
• A structured implementation process was developed to ensure consistency, transparency, and reproducibility in attempted replications.

Main Results:

• Approximately 30 attempted replications of RCTs using nonrandomized RWE are estimated to be completed after feasibility analyses.
• This initiative represents the first systematic evaluation of nonrandomized RWE's ability to replicate multiple RCTs.

Conclusions:

• The study's results will offer crucial insights into the reliability of nonrandomized RWE from claims data for regulatory purposes.
• Understanding the strengths and limitations of nonrandomized RWE is essential for informing FDA guidance on its use in decision-making.