What FDA's Real-World Evidence 2025 Update Means for Medical Device Companies

By Tracy Case, MS, MBA, with Jose Pablo Morales, MD contributing

On December 15, 2025, the U.S. FDA "...removed a barrier to real-world evidence (RWE) in medical device submission. In its updated guidance, “Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices.” The agency policy position is now to accept RWE without always requiring submission of identifiable individual patient-level data from real-world data (RWD) sources. This change unlocked broader use of de-identified, large-scale registries, claims databases and electronic health record (EHR) networks to support a wide range of regulatory strategies and applications.

Veranex can help you understand and leverage these options before finalizing your clinical development plan. By leveraging established networks, we can make a meaningful difference in your product development program to keep your product in the market, expand your indications, or seek a new indication.

1. Post-market Surveillance Strategy

The FDA has long recognized and encouraged the use of RWE to support post-market surveillance (PMS) for medical devices, building on foundational frameworks and evolving policies.

The FDA's final guidance outlines the key success criteria for using RWE derived from RWD to support PMS for medical devices. This includes fulfilling post-approval studies (PAS), addressing Section 522 PMS orders, monitoring safety signals, and generating evidence for long-term performance or labeling updates.

To successfully use RWE for PMS of medical devices under FDA regulations, sponsors must ensure the underlying RWD is relevant and reliable. The study design must be fit-for-purpose, with a clear, prespecified protocol, rigorous analysis, and early FDA alignment through Q-Submissions.

Effective teams and their partners accelerate and de-risk this process by providing end-to-end support:

• Developing tailored RWE strategies and integrated evidence plans that align regulatory, clinical, and commercial needs;  
  

• Assessing and sourcing high-quality RWD sources, designing FDA-aligned PMS protocols;

• Preparing for and facilitating pre-submission meetings; managing data integration, quality controls, and bias mitigation;

• Compiling robust submission packages to maximize acceptance and efficiency.

2. Indication Expansion Strategy

If there is an established registry in your device space, particularly one that captures outcomes beyond the currently approved indications, these real‑world data may support an indication expansion without the need to initiate a new pivotal trial.

Success depends on demonstrating to the FDA that the existing evidence meets their standards for relevance and reliability, and that the RWE is fit-for-purpose.

How This Approach Works

The core mechanism is extraction and submission of real-world evidence from your ongoing registry. During routine registry data collection, outcomes in off-label or extended use populations were captured as practice of medicine on clinical sites participating in the registry. Rather than launching a separate trial, you can develop a clinical and statistical plan to look at the registry data with the aim to meet the regulatory standards. With a well-defined plan in place, we can assist you with the analyzis and submission of this evidence to support a labeling expansion.

Here's what makes this approach viable: you're not asking the FDA to accept lower evidence standards. You're demonstrating that the evidence they need already exists in a properly structured registry that captures the right clinical variables, follows appropriate protocols, and documents outcomes that meet FDA standards for real-world evidence submissions.

The critical step is crafting a compelling regulatory justification that positions your RWD as both relevant and reliable, that the RWE is fit-for-purpose. Focus on demonstrating: 1) data provenance and governance, 2) clinical meaningful endpoints, 3) adequate follow-up and population representation, 4) methods to mitigate bias and confounding, 5) quality and monitoring standards. When these elements are well-justified in the submission, FDA has accepted registry-derived RWE for indication expansions in cardiovascular devices.

Strategic Planning Implication

For organizations with an established registry network, the focus should be on proactive assessment and enhancement of justification strategies. This requires evaluating current data against FDA’s expectations and preparing pre-submissions to obtain FDA’s alignment. Many companies collect valuable real-world data for post-market surveillance or physician-led studies but overlook building the documentation needed for regulatory reuse. Early review and gap analysis can avoid the need for supplemental trials later.

A pattern emerges repeatedly: companies invest heavily in registries for post-market surveillance or physician preference studies, but they don't always have the right data elements and quality controls that would make that same data acceptable as regulatory evidence. Then two years later, they realize they need exactly the data they've been collecting, but it's not structured properly for submission as an indication expansion. This pathway is most viable when:

This pathway may not be suitable when:

• Data quality meets 21 CFR Part 11 and can demonstrate robustness under FDA review.

• The registry protocol already captures comprehensive safety and effectiveness data relevant to the expanded indication.

• The indication expansion is a logical extension of the currently approved use.

• Real-world conditions in the registry closely align with the current clinical practice.

This pathway may not be suitable when:

• Fundamental shifts in mechanism of action, target anatomy or patient population (not a “logical extension” of current use).

• Some situations requiring tightly controlled randomization/blinding to answer the key safety/effectiveness question.

• Registries with high [absence] of data, inconsistent data dictionary, or weak registry infrastructure.

3. New Product Approval Strategy

If a pivotal clinical study under an investigational device exemption (IDE) is anywhere in your development roadmap for new product approval, exploring Option 3 before you finalize your trial design could unlock acceleration potential. Traditional, stand alone, pivotal trials often demand large-scale prospective enrollment, extended timelines, and substantial budgets. Yet a more efficient alternative, embedding the clinical IDE trial into the registry infrastructure, has long been discussed with FDA and remains underutilized.

How the Model Works

The core idea integrates a prospective component (the IDE study) with a large, established coordinated registry network (or similar real-world data source) that provides the foundational infrastructure — such as electronic data capture (EDC) systems, principal investigator (PI) networks, site workflows, standardized data elements, and ongoing surveillance capabilities. This approach aligns with FDA's recognition of fit-for-purpose RWE in device evaluations for new product approvals.

Prospective trial: the prospective trial focuses on FDA's key requirements for high-quality evidence: enrollment of patients in the intended population receiving the new device (or intervention), and prospective collection of essential device-specific procedure details, primary/secondary outcomes, follow-up assessments, adverse events, and safety/effectiveness endpoints. The prospective arm delivers direct, standardized evidence on the device in real-world use.

Registry: the registry serves as the operational backbone, supplying tools and processes to support study conduct. Key infrastructure includes:

• EDC systems and automated/semi-automated data capture (e.g., established case report forms with routine clinical variables).

• PI and site networks for patient identification, recruitment, and real-time screening of eligible cases.

• Standardized workflows for data accrual, quality checks, and long-term follow-up without redundant collection.

The model is governed by a pre-specified protocol that explicitly defines:

• Which data/elements are prospectively collected (e.g., device-specific details, targeted outcomes).

• How registry infrastructure supports the study (e.g., EDC integration, site coordination, automated elements).

• Statistical methods to ensure validity and minimize bias

This model significantly improves trial efficiency and reduces cost compared to fully standalone trials, accelerates enrollment, and produces scientifically robust evidence suitable for regulatory decisions.

For example, the SAFE-STEMI for Seniors trial (Rymer et al., 2019) represents a real-world example of implementing a prospective randomized investigational device exemption study within a Coordinated Registry Network infrastructure. The trial demonstrated faster enrollment, significantly reduced site workload and trial costs by around 30%. Such designs enable streamlined execution by minimizing redundant efforts and leveraging routine clinical workflows.

What's Required to Make This Work

This approach requires early planning and the right partnerships. You need:

• Registry infrastructure that captures the relevant patient population and outcomes

• Access to the registry data

• Study design that clearly delineates what data comes from registry versus prospective collection

• FDA alignment on your approach through a pre-submission meeting

• Operational capabilities to integrate registry data with your prospective study data

The companies that benefit from this approach are those who explore these options during early-stage clinical program assessment, not after they've committed to a traditional trial design.

FDA Signals on These Approaches

"From my experience at the FDA, I witnessed firsthand the agency's strong interest in registry-based approaches that leverage real-world data infrastructure," notes Pablo Morales, MD, Chief Medical Officer at Veranex and former Senior Medical Advisor in the FDA's Office of Clinical Policy. "All three approaches are viable and can be considered depending on the medical product, the stage of product development and evidentiary needs for the labeling change. The FDA has signaled clear support for these approaches when designed appropriately."

Early engagement with FDA via pre-submission meetings is essential to align on the real-world data source, the clinical protocol, the data integration and analysis plan, and the proposed indication for use, to ensure the data is fit-for-purpose.

For cardiovascular device companies, the question isn't whether real-world evidence will play a role in your development strategy. It's whether you'll recognize the opportunities early enough to actually benefit from them, or whether you'll discover these pathways exist after you've already committed millions to a conventional approach.

Questions about how these approaches might apply to your specific cardiovascular device program? Contact Tracy Case and the Veranex clinical research team to discuss your development strategy and explore whether real-world evidence pathways could accelerate your timeline.

About Clinical Research at Veranex
Clinical trials represent some of the largest investments in medical device development, and execution failures waste millions while patients wait. Veranex Clinical Research provides end-to-end CRO services for medical devices and IVDs, from trial design and site selection through monitoring, data management, and biostatistics. Our device-savvy CRAs understand surgical learning curves, UDI traceability, and ISO 14155 compliance in ways pharma-focused CROs do not. Upstream, our clinical teams build on human centered designs, human factors, preclinical evidence and regulatory strategy to design trials with endpoints that satisfy both regulators and payers, informed by commercial strategy insights on coverage requirements. Downstream, clinical data flows into regulatory submissions, medical writing for CERs and PERs, and HEOR models that support reimbursement applications. When clinical, regulatory, and commercial specialists work side by side, clinical trial design reflects the full picture from the start, compressing approval-to-coverage timelines making your business go faster.

About the authors:

Tracy Case is Director of Clinical Affairs. Tracy joined Veranex in 2025 and has over 15 years of experience in the medical device and life sciences industries. Prior to joining Veranex, Tracy held leadership roles at Medtronic and BD, where she led strategic initiatives in clinical evidence generation for new product development, indication expansion, and post-market surveillance.

With extensive expertise in designing and managing a wide range of clinical programs, Tracy has led projects across various stages, including feasibility studies, First-In-Human (FIH) studies, pivotal studies, post-approval studies, registries, real-world evidence (RWE) studies, and investigator-initiated studies. Her experience spans a diverse set of technologies, particularly in the areas of interventional cardiology, renal denervation, coronary stents, drug-eluting balloons, advanced energy devices, breast oncology devices, implantable devices, hemostatic devices, surgical mesh, and IVD products.

At Veranex, Tracy supports clients’ clinical and regulatory projects, including U.S. and international clinical study programs, from Early Feasibility Studies (EFS) to First-In-Human (FIH)/Feasibility Studies (FS) to pivotal trials and real-world evidence (RWE) initiatives in pursuit of medical device commercialization.

Jose Pablo Morales, MD is Chief Medical Officer at Veranex. Dr. Morales previously served in senior roles at FDA's Division of Cardiovascular Devices, where he supported and led some collaborations with registry networks such as the International Consortium of Vascular Registries (ICVR) and the Registry Assessment of Peripheral Intervention Devices (RAPID). These experiences involved harmonizing prospective and real-world data to support regulatory decision-making in cardiovascular devices. In his current role, he continues to advance registry-based strategies for efficient evidence generation.