When every respondent in a survey agrees, it’s more than a trend; it’s a mandate. In the 2025 TriNetX and studioID survey of 150 senior biopharma executives, all participants agreed that real-world evidence (RWE) has the potential to improve regulatory submissions. This rare unanimity underscores the urgency for sponsors to integrate RWE more strategically into their regulatory playbooks.
Why RWE Has Regulatory Appeal (and Where It Excels)
Bridging Gaps Trials Can’t Reach
RWE’s unique strength lies in its ability to fill critical evidence gaps that randomized controlled trials (RCTs) cannot always address. Whether due to ethical constraints, feasibility issues, or limitations in trial design, traditional studies don’t always tell the full story, particularly in rare diseases, vulnerable populations, or when evaluating long-term outcomes. RWE, grounded in real-world data (RWD) sources like electronic health records (EHRs), health insurance claims data, and registries, provides a valuable supplement (or in some cases, decisional) information when trials fall short.
Uncovering Insights from the Real World
While clinical trials offer insights under tightly controlled conditions, RWE brings a complementary perspective. It helps sponsors contextualize patient burden and treatment gaps, identify appropriate outcomes for trials, understand the background rate of possible adverse events to put trial data in broader context, and to support post-approval requirement discussions with robust RWD, potentially avoiding or minimizing onerous, costly, and sometimes impossible post marketing requirements.
Keeping Tabs After Approval
RWD captures how marketed therapies perform across diverse, real-world populations that include individuals with various comorbidities or complex care journeys. This broader lens helps sponsors paint a more complete picture of a treatment’s safety, effectiveness, and everyday impact, which are critical inputs not only for regulators, but also for public and private payors, clinicians, and policy makers. The integration of RWE into Health Economics and Outcomes Research (HEOR) frameworks is helping the industry assess value, inform access decisions, and elevate evidence generation strategies across the product lifecycle.
Post-market commitments are another area where RWE delivers. Increasingly, regulators require ongoing data to confirm benefit-risk profiles beyond approval. RWE supports this by enabling continuous monitoring, assessing long-term safety and effectiveness, and informing potential label expansions. As public and political scrutiny grows, especially around high-profile products like pediatric vaccines, ongoing real-world monitoring is becoming essential to maintaining trust and transparency.
Accelerating Access with Smarter Evidence
RWE can also reduce time to submission for select indications. For pathways such as accelerated approvals, rare disease treatments, or supplemental indications, it can streamline development by supplementing or, in some cases, substituting for trial data. This integrated approach has the potential to shorten timelines, improve decision-making, and expedite patient access to innovative therapies.
What Regulators Expect
The U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and other regulatory agencies have taken various steps to support the use of RWE, issuing frameworks and guidance documents that outline expectations and acceptable standards. But regulatory documents and supportive public statements don’t translate to acceptability by front-line regulatory decision-makers. Sponsors must be prepared to meet high regulatory expectations with scientific rigor, methodological clarity, patience, and ongoing engagement to help regulatory staff who are comfortable with clinical trial data become comfortable with the inherent uncertainty around RWD and the related methods.
This begins with ensuring the data is fit-for-purpose for the intended use and study design. RWD must offer longitudinal depth, clear provenance, and appropriate capture of key data elements across care settings and time. Methodologically, study designs should be robust and grounded in transparent, reproducible analytics. Regulators are not simply looking for results; they’re looking for results they can understand and trust, supported by clear reasoning and credible data.
How to Make RWE Submission-Ready
Making RWE regulatory grade requires discipline across every phase of evidence generation. Five critical steps can guide sponsors toward more successful submissions:
- Ensure Data Integrity
The foundation of any regulatory-grade study is well-documented, high-quality, fully characterized, and harmonized data. Sponsors must scrutinize data sources for completeness, accuracy, and alignment with the research question and proposed methods. This includes assessing how the data are captured, identifying potential biases, and ensuring the population reflects real-world clinical scenarios. Ongoing quality assurance and transparent documentation are essential. - Use Validated Methods
Scientific credibility hinges on methodological rigor. Sponsors must rely on accepted statistical and epidemiological approaches that are well understood and broadly endorsed. Analytical tools and models must demonstrate robustness through sensitivity analyses and justification of assumptions. - Align Early with Regulators
Early engagement with agencies helps avoid missteps later. By seeking input on data sources, endpoints, and analytic approaches before initiating studies, sponsors reduce risk and foster alignment on expectations. These touchpoints create a shared understanding that can accelerate the review process. This engagement includes topics around data and methods, but also around regulatory pathways and flexibility. It’s good practice to also bring regulatory expertise to the table. - Document Everything
Transparency is non-negotiable. From cohort creation to analytic code, every step must be clearly recorded and developed with sharing in mind. Regulators expect access to all relevant material from programming code to standard operating procedures (SOPs) to data provenance documentation to the row-level patient data. - Match Use Case to Evidence Strength
Strategic discernment is vital. Not every research question is suitable for observational data. Knowing when and how to apply RWE (and when not to) is essential to maintaining scientific integrity and regulatory confidence.
With the right data, methods, and strategy, RWE generation can do more than support a regulatory submission; it can elevate it. The future of regulatory science is already unfolding, and RWE is at its core.
Ready to explore additional trends shaping the future of biopharma? Download the full TriNetX 2025 Industry Survey Report to discover the latest in AI adoption, patient-centricity, and the evolution of trial design.
About Jeffrey Brown, PhD
With more than 25 years of experience in research and consulting, Jeff is an internationally recognized expert in the use of RWD to support the evidentiary needs of regulatory agencies and medical product sponsors and an expert in the assessment of data quality of RWD resources.