What clinops professionals need to know
The FDA will now publish FAERS adverse event data daily, a shift aimed at faster and more transparent safety monitoring. In parallel, the agency released over 200 previously confidential CRLs, highlighting deficiencies that prevented drug approvals. While these steps mark progress in transparency, recent CRLs to companies like Replimune and Capricor have raised concerns about increased scrutiny of trial design and shifting expectations from FDA reviewers. Clinical operations professionals should anticipate closer regulatory evaluation of study design, sample sizes, and data robustness.
The FDA has announced it will now be publishing adverse event data from the FDA Adverse Event Reporting System (FAERS) on a daily basis. The agency stated that this action represents a “significant step forward” in modernizing safety monitoring as well as its continued commitment to improving transparency.1
FDA launches daily FAERS reporting
In an FDA news release, Commissioner Marty Makary, MD, MPH, said: “Adverse event reporting should be fast, seamless, and transparent. People who navigate the government’s clunky adverse event reporting websites should not have to wait months for that information to become public. We’re closing that waiting period and will continue to streamline the process from start to finish.”
The FDA's principal database for collecting and analyzing adverse event reports, FAERS, encompasses an array of information such as:
- Serious medication errors,
- product quality complaints for prescription drugs and therapeutic biologics,
- and reports submitted by healthcare professionals, consumers, and manufacturers.
FDA increases transparency with CRL publications
Earlier in July, the FDA revealed another initiative geared towards increasing transparency, publishing over 200 complete response letters (CRLs) issued between 2020 and 2024 in response to drug and biologic applications.
In an FDA news release from the time, Makary said: “For far too long, drug developers have been playing a guessing game when navigating the FDA. Drug developers and capital markets alike want predictability. So today we’re one step closer to delivering it to them, with an ultimate goal of bringing cures and meaningful treatments to patients faster.”2
Prior to this announcement, CRLs were only shared with product sponsors, limiting broader industry visibility into the specific deficiencies that prevented approval.
A 2015 analysis conducted by the FDA revealed that 85% of safety and efficacy concerns raised in CRLs were not publicly disclosed by sponsors. Furter, in about 40% of cases in which the agency called for new clinical trials to address safety or efficacy issues, details regarding the issues were not released to the public.2
Industry response and concerns
While the FDA has made its approach to radical transparency known through these initiatives, there are still questions regarding the agency’s execution. Around the same time the 200 CRLs were made available through openFDA, Replimune and Capricor were handed CRLs which both companies considered to be surprising.
The CRL to Replimune concerned its BLA for RP1 (vusolimogene oderparepvec) in combination with nivolumab, noting that the Phase I/II IGNYTE clinical trial (NCT03767348) did not constitute an adequate and well-controlled study.
Meanwhile, in the CRL to Capricor for Deramiocel, the FDA cited the need for additional data, despite the cell therapy being granted Priority Review in March, which was supported by findings from the Phase II HOPE-2 study (NCT03406780).
Implications for trial design
In an earlier statement to Applied Clinical Trials regarding these CRLs, Craig Lipset, co-chair, Decentralized Trials & Research Alliance (DTRA), said: “This is particularly challenging for those who have based development strategies and investments on the outcomes of meaningful communications strategies with FDA stakeholders prior to 2025. It raises questions for developers today as to whether past understandings still hold true, as well as the potential risks and benefits of re-engaging with FDA on active development programs based on those past agreements.”
Despite the FDA’s efforts to improve transparency, many in the industry are still unclear on the agency’s views regarding trial design. Outside of the recently issued CRLs, the FDA has also made a clear stance on tightening up studies for vaccines.
In a video interview with ACT regarding the FDA’s recent actions, Meri Beckwith, Co-CEO, Lindus Healt,h emphasized that there could be even more scrutiny of trial design on the horizon as the agency transitions to new reviewers.
“…maybe over the next year or two, there's a pretty consistent pattern of the FDA rejecting more studies that aren't controlled or insisting on more robust results, more carefully scrutinizing sample sizes, those kinds of things, remains to be seen,” he said. “My view is that these decisions, it's just unpredictability, the result of one set of reviewers, maybe transitioning off or out of the FDA, and then a different set of reviewers with a different perspective coming in.”
References
1. FDA Begins Real-Time Reporting of Adverse Event Data. News release. FDA. August 22, 2025. Accessed August 25, 2025. https://www.fda.gov/news-events/press-announcements/fda-begins-real-time-reporting-adverse-event-data
2. FDA Embraces Radical Transparency by Publishing Complete Response Letters. News release. FDA. July 10, 2025. Accessed August 25, 2025. https://www.fda.gov/news-events/press-announcements/fda-embraces-radical-transparency-publishing-complete-response-letters
