Real-World Evidence in Medical Device Approvals: Strengthening the Path to Regulatory Success

Expanding the Role of Real-World Evidence in Medical Device Regulation

Regulatory agencies are placing greater emphasis on real-world evidence (RWE) to complement randomized controlled trials (RCTs) in evaluating medical devices. RCTs provide invaluable information on efficacy; however, they do not always capture information on effectiveness, such as how a device performs across varied patient populations or in routine clinical practice. Real-world data (RWD) fills these gaps by offering a broader view of safety, effectiveness, and long-term outcomes beyond controlled trial settings.

The increasing reliance on RWE brings both opportunities and challenges. RWE must be rigorous, transparent, and reproducible to be relevant in regulatory decision-making. Not all RWE studies meet these criteria, and inconsistencies in data sources and methodologies can undermine their credibility. Ensuring that RWE studies adhere to scientific and regulatory standards is essential for RWE use in pre-market approvals, post-market surveillance, and health technology assessments (HTA).

NEST’s Role in Catalyzing RWE for Medical Devices

The National Evaluation System for Health Technology (NEST) Coordinating Center was created through a U01 Cooperative Agreement with the FDA and is helping establish clear scientific and methodological approaches for using RWE in medical device evaluation. Through its Medical Device Real-World Evidence Marketplace, NEST provides medical device manufacturers access to high-quality, real-world data sources and facilitates connections with research partners. This effort increased confidence among manufacturers and regulators that RWE studies are generated and applied in a way that meets regulatory and scientific expectations.

Key areas of focus include:

• Defining criteria for regulatory-grade RWE: Ensuring data sources meet accuracy, completeness, and reliability requirements.
• Facilitating collaborations between manufacturers, regulators, and research organizations: Strengthening the integration of RWE into regulatory decision-making.
• Advancing methodological rigor: Developing best practices to improve study designs and minimize bias in real-world studies.

NEST’s work is critical in supporting the broader adoption of RWE in medical device regulation. It provides a structured approach that helps manufacturers navigate evolving regulatory requirements.

Aetion’s Role in Generating Regulatory-Grade RWE

As part of NEST’s Medical Device Real-World Evidence Marketplace, Aetion® collaborates with NEST and medical device manufacturers to ensure their RWE studies meet the highest scientific and regulatory standards. By applying validated epidemiologic methods and causal inference techniques, Aetion’s approaches strengthen the reliability of real-world studies used in regulatory submissions.

Aetion works with NEST to implement the NEST Mark approach for evaluating the regulatory feasibility of RWE studies, helping manufacturers:

• Identify data sources that align with regulatory expectations
• Structure real-world studies to generate credible, interpretable findings
• Apply rigorous methodologies to ensure transparency, reproducibility, and regulatory alignment

Aetion’s collaboration with NEST on this approach helps manufacturers reduce uncertainty and strengthen regulatory submissions by ensuring that RWE studies meet the highest scientific standards.

RWE as a Cornerstone of Medical Device Evaluation

Regulatory agencies expect well-designed RWE studies to support medical device submissions and post-market surveillance. Manufacturers must incorporate real-world data strategies into their evidence-generation plans to keep pace with these expectations. This approach allows for:

• A more efficient regulatory review process by complementing clinical trial data with real-world insights
• Stronger post-market safety monitoring through ongoing real-world surveillance
• Reduced time to market by structuring the approach to evidence generation to support regulatory approval pathways

Organizations such as NEST and Aetion provide the expertise, data infrastructure, and analytical frameworks necessary to elevate RWE's role in regulatory decision-making. 

Aetion’s Expertise in Regulatory-Grade RWE

Aetion’s leadership in regulatory-grade RWE is demonstrated through its collaborations with medical device manufacturers, regulators, and research organizations. The application of high-quality RWE in regulatory decision-making has already shaped key approvals and labeling updates, reinforcing the value of real-world data in supporting safety and effectiveness claims.

For instance, regulatory decisions based on RWE have included retrospective analyses of long-term survival rates and comparative effectiveness assessments. By leveraging structured, de-identified healthcare claims data and applying rigorous causal inference methodologies, Aetion has contributed to regulatory submissions that resulted in labeling changes reflecting real-world clinical outcomes. These applications demonstrate how well-designed RWE studies can complement traditional clinical trial data, providing regulatory bodies with a comprehensive understanding of device performance in real-world settings.

As expectations for RWE evolve, Aetion remains committed to ensuring that manufacturers can access scientifically rigorous, transparent, and reproducible real-world studies that meet the highest regulatory standards.

For more information on how Aetion supports medical device manufacturers in leveraging RWE for regulatory success, contact us today.