While uses for AI in pharma have ramped up, the FDA has been working to develop standards to inform the industry on future regulatory frameworks for the technology. Now, the FDA’s Center for Drug Evaluation and Research is launching a new solution to may help address this gap.
In April, the agency announced the creation of the Center for Clinical Trial Innovation (C3TI), which aims to boost innovative approaches to clinical trials. The center will act as a hub within CDER to implement efficiencies by allowing trial sponsors to work with CDER staff. Initial demonstrations of the program can be used as case examples for future implementation.
“We have championed innovation for a long time,” Kevin Bugin, lead for C3TI and deputy director of operations in the office of new drugs, told PharmaVoice in an emailed statement. “In fact, CDER has been a leader in navigating the complexities of a rapidly changing drug development ecosystem. However, as drug development continues to evolve, clinical trials must evolve accordingly.”
The center’s launch includes three project areas that may open the door to more AI uses in clinical trial and drug development programs, including point-of-care or pragmatic trials, Bayesian analyses — which uses “multi-level statistical models” to describe data elements — and trials leveraging selective safety data collection.
“Through its engagement and coordination efforts, C3TI will also work to further enhance the adoption of innovations involving AI/[machine learning] and support the development of new CDER AI initiatives as related to clinical trials,” Bugin said. “We will also facilitate information sharing with external parties about AI/ML as appropriate, and will support knowledge sharing internally through various mechanisms, such as discussion forums and communications.”
Clinical trials lack innovation
In general, clinical trials are “not very innovative,” according to Charles Fisher, CEO of Unlearn.AI, an AI company that creates digital twins and offers a web-based app for clinical trial planning.
“By and large, clinical trials are run by really large pharmaceutical companies,” Fisher said. “The big pharma companies don't move very fast [so] it always takes them a long time to adopt new things.”
However, Big Pharma argues that the regulatory environment around clinical trials has been one of the biggest impediments to innovation.
“One reason for the lack of consistent, widespread adoption of innovative approaches is that efforts to revise FDA’s regulations have not kept up with the breadth and pace of change and advancement in the industry,” said Eli Lilly’s senior vice president of clinical capabilities Janelle Sabo in a public comment to the FDA.
C3TI isn’t the agency's first foray into attempts at innovation. In the last few years, the FDA has launched a string of programs aiming to improve clinical trials, including the Complex Innovative Trial Design Paired Meeting Program, which was introduced in 2022 and aimed to advance “the use of complex adaptive, Bayesian and other novel clinical trial designs;” the Innovative Science and Technology Approaches for New Drugs Pilot Program, which supports “novel approaches to drug development” such as AI-based algorithms; and the Fit-for-Purpose Initiative, which creates a regulatory pathway for drug development programs that use “dynamic tools.”
C3TI is specific to innovation in clinical trials, but the program may have “similar objectives” to past programs, the FDA said.
“There’s really broad confusion within the whole industry as to how AI can be used in clinical trials."
Charles Fisher
CEO, Unlearn.AI
“We see C3TI as a continuing evolution of our longstanding clinical trial innovation efforts,” Bugin said. “By acting as a hub, C3TI plans to strengthen the implementation of current innovation efforts and encourage the development of new ones through enhanced communication and collaboration.”
Despite this history, some companies have found these initiatives lacking in real-world guidance.
“Currently, most guidances on innovative approaches provide an outline of FDA expectations and concerns about the uncertainties of the approach, but lack practical instruction on implementation,” Dr. Mwango Kashoki, senior vice president, global head of regulatory strategy at Parexel, wrote in the company’s comment to the FDA.
And the FDA’s top-down approach to innovation may not be impacting how trials are run.
“The agility of the FDA regulatory review process impacts innovation,” Kashoki’s comment continued. “Although we are seeing a pragmatic, patient-focused approach from FDA leadership, this is not filtering down to the division and individual FDA staff member levels.”
Informing regulations
As part of the launch, CDER has said C3TI will include additional touchpoints with CDER staff, with expanded opportunities for “enhanced communication and collaboration.”
This belief that the FDA isn’t willing to accept innovation may be a false perception held by the pharma industry, according to Fisher.
“My experience, working with both the FDA and the [European Medicines Agency], has been that they're quite open to innovation, often encouraging innovation, but that's not the perception in the industry,” Fisher said. “Any programs that the regulators create to try to combat that perception and encourage the development of new innovative approaches is very welcome.”
With the addition of C3TI comes the question of how this initiative is different from the FDA’s past forays in innovation, and how the center will add clarity to the regulatory framework — something pharma companies say is impacting their decisions to get involved in pilot programs and demonstration projects.
“It is worth noting that there appears to be a disconnect between the public statements made by senior FDA leaders advocating for innovative approaches, and the feedback and views expressed within the review divisions and medical product centers,” Genentech said in its comment to the FDA. “Ultimately, such inconsistent feedback creates uncertainty and regulatory risk, which can discourage investment and participation in pilot programs.”
Without guidance from the FDA or CDER, the future of AI in clinical trials can’t be hammered out completely, Fisher said.
“There's really broad confusion within the whole industry as to how AI can be used in clinical trials, and even what it is, how it's going to be regulated,” Fisher said.
According to CDER, C3TI and its goals could help inform how the agency ultimately regulates AI.
“Initially, C3TI is considering how our regulatory framework could be optimized to support the rapid evolution in clinical trial design and conduct and the use of technological innovations,” Bugin explained. “We will consider whether targeted changes could help further accommodate and advance modern operational approaches to clinical trials; facilitate the incorporation of technological innovations that promote efficiency and enable diversity; and emphasize the importance of good risk assessment and management principles to the quality of clinical investigations.”
As pharma continues to leverage AI, some companies are seeking more information from the FDA on how to move forward.
“An important challenge is that although industry is moving (and needs to move) forward quickly with [AI], it will be many years before FDA issues guidance,” Kashoki wrote. “The FDA needs to share more quickly with industry and other stakeholders what the agency is learning, what are their areas of greatest focus and concern, and for what issues do they want more detailed information from industry.”
