The US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) on Friday held a webinar reviewing the agency’s real-world evidence (RWE) framework, which deals primarily in the postmarket space for drugs and biologics.
The agency unveiled
its RWE framework last December to provide a high-level view of how it is looking at the use of real-world data.
Jacqueline Corrigan-Curay, director of the Office of Medical Policy within CDER, explained the wide spectrum of real-world data (RWD) – from supplementing traditional randomized, controlled trials, or single-arm studies with historical controls, or the use of observational studies, with a registry or retrospective analysis of data.
Corrigan-Curay also raised questions about some observational studies.
“There has been a recognition that these database studies can be quite easy to perform, and can be replicated using complex statistical analyses, opening up the possibility that the data could be reanalyzed over and over until the desired result is obtained,” she said.
“This is something that’s very difficult to do when you’re talking about clinical trials that are conducted over many years and for which the protocol is preregistered in a public database. Therefore, we and other professional organizations involved in these studies are thinking about transparency and what does that look like. Transparency about study design and analysis before execution will be critical for ensuring confidence in the result and in sharing that with FDA before the study is executed,” she added.
But she noted that what transparency will look like from a public-facing standpoint “will require more discussion.”
As far as what’s to be expected in the future, she also discussed how CDER is preparing three guidance documents:
- On observational study designs using RWD, including whether and how these studies might provide RWE to support product effectiveness in regulatory decision making
- On considerations for using RWD in randomized clinical trials for regulatory purposes, including use of pragmatic design elements
- On the use of RWD to generate external control arms
David Martin, associate director for real world analytics in CBER’s Office of Medical Policy, said guidance will be made public before the end of 2021.
Corrigan-Curay also discussed FDA demonstration projects related to RWE, which come in three buckets: Data, RWE tools and RWE study design. One of the projects FDA is funding at UC San Francisco
is integrating a standards-based tool into the electronic health record (EHR) to combine health care and research as part of the breast cancer trial called I-SPY.
Sean Khozin, acting associate director of oncology, regulatory science and informatics at FDA’s Oncology Center of Excellence, previously said
an upcoming guidance document will specifically address the use of data from EHRs. Another guidance document on mobile technology is also currently under development, while another will look at the use of registries.
On a question from the audience Friday about use of RWD as external controls in a confirmatory study, in lieu of a placebo-controlled confirmatory study for full approval, she said FDA is “interested in those studies in which a single-arm study is appropriate to look at whether the control could be an external control from RWD,” but the question of whether a placebo-controlled confirmatory study is necessary is a review division question and would be decided on a case-by-case basis.
Another question asked about cross-collaboration among centers on RWE and Corrigan-Curay said the RWE framework is used across CBER and CDER, “but we make a concerted effort to have regular contacts with colleagues at CDRH to make sure we’re moving in similar direction.”