FDA releases latest figures on real-world evidence use in regulatory submissions

The latest FDA report shows a substantial increase in real-world evidence (RWE) submissions to CDER, continued use of RWE in regulatory decision-making, and growing diversity in study designs used to support drug development.

The Baseline

• CDER received 31 RWE protocol submissions in FY2025, nearly three-times the number reported in FY2024, while ten NDA/BLA submissions containing RWE received regulatory action.
• RWE contributed to four FDA approvals, and the annual analysis included externally controlled trials and a randomized controlled trial for the first time, alongside continued use of observational studies.
• The report forms part of the FDA's broader landscape analysis of RWE use and reflects the agency's ongoing commitment to transparency around how RWE informs regulatory decision-making.

New data from the US Food and Drug Administration (FDA) indicates a growing use of RWE across drug development, with a notable rise in submissions to Center for Drug Evaluation and Research (CDER) and the continued use of RWE to support regulatory decision-making.

The agency's latest annual summary of RWE submissions to CDER and the Center for Biologics Evaluation and Research (CBER), published under its Prescription Drug User Fee Act (PDUFA VII) commitments, provides an overview of submissions containing real-world data (RWD) intended to support regulatory decisions for drugs and biologics during Fiscal Year (FY) 2025.

The publication follows an earlier this month to its public catalogue of RWE examples used in regulatory decision-making, which added new case studies from across multiple product centers. Both initiatives form part of the agency's broader landscape analysis of RWE use and are intended to provide stakeholders with greater transparency into how RWD are being incorporated throughout the product lifecycle and applied in regulatory evaluations.

The latest figures suggest that while observational studies remain the predominant approach, the range of study designs and regulatory applications continues to expand. The substantial increase in CDER activity, coupled with multiple approvals in which RWE contributed to FDA decision-making, further illustrates the growing role of RWD in the evaluation of drugs and biologics.

Strong growth in CDER submissions

The FY2025 data show a substantial increase in RWE activity within CDER compared with previous years.

In contrast, activity within CBER declined from the elevated levels observed in FY2024.

CDER: Expansion across the product lifecycle

CDER received 31 protocol submissions containing RWD in FY2025, nearly three-times the number reported in FY2024. These submissions included both new protocols and protocol amendments adding RWD to existing studies.

Of the 31 submissions, 15 were intended to support effectiveness and 16 focused on safety. The largest proportion were designed to fulfil postmarketing obligations, with 16 supporting postmarketing requirements (PMRs) and eight supporting postmarketing commitments (PMCs).

Four protocols were intended to support the demonstration of safety and/or effectiveness for products not yet approved by FDA, while three were designed to support labeling changes for approved products, including modifications to indications, dosing, and expansion into new patient populations.

The data also provide insight into the types of RWD being used. Registries were the most frequently cited source, appearing in 12 protocol submissions, followed by electronic health records (11) and medical claims data (7). Ten submissions used other data sources.

One notable development in FY2025 was the appearance of study designs not previously reported in the FDA's annual analysis. While non-interventional observational studies continued to dominate, accounting for 25 of the 31 submissions, the report also included one randomized controlled trial and five externally controlled trials. The emergence of these designs reflects the growing diversity of approaches being explored for generating RWE in regulatory settings.

RWE contributes to multiple regulatory decisions

CDER reported ten NDA or BLA submissions containing RWE that received regulatory action during FY2025, compared with just one in FY2024.

The ten submissions included four approvals in which RWE contributed to FDA's decision-making: ACETADOTE (acetylcysteine), ONAPGO (apomorphine), ISTURISA (osilodrostat), and GAMIFANT (emapalumab-lzsg).

The total also included one approved application in which RWE was submitted but did not contribute to FDA's decision, four complete response actions, and one refuse-to-file decision.

As in previous years, the FDA notes that the reported figures include submissions where RWE was present irrespective of whether it influenced the regulatory outcome.

CDER also received six final study reports intended to satisfy PMRs or PMCs, continuing a trend first observed in FY2024 and highlighting the ongoing role of RWE in postmarketing evidence generation.

CBER: Activity lessens following previous increase

After the sharp rise reported in FY2024, CBER received eight protocol submissions containing RWD in FY2025.

The submissions were evenly split between effectiveness and safety objectives, with four protocols focused on each. Four submissions were intended to satisfy PMRs and two supported PMCs.

Two protocols aimed to support the demonstration of safety and/or effectiveness for products not previously approved by FDA, while two were intended to support labeling changes, including indication expansion and modifications.

The data sources used mirrored those seen in CDER, including electronic health records, medical claims, and registries. All CBER submissions were based on non-interventional observational study designs.

Unlike FY2024, when CBER reported two biologics license applications incorporating RWE, there were no NDA or BLA submissions containing RWD or RWE for which CBER took regulatory action in FY2025. The center received one final study report intended to satisfy a PMC.