The FDA today announced a new initiative to allow its reviewers to access information from clinical trials in real time, with two major industry players already taking part in a pilot program.
AstraZeneca and Amgen are both conducting trials that will report safety and efficacy signals to the FDA as they come in, the agency said, rather than waiting for data to be collected, analyzed and submitted.
“We’re announcing a bold new approach that could fundamentally transform this clinical trial landscape,” FDA Commissioner Marty Makary, M.D., said on a Tuesday morning call with reporters. “FDA regulators will view safety signals and clinical endpoints in the cloud in real time as they are occurring. This is one important step towards our broader goal of seeing more continuous trials.”
The effort stems from the well-known, lengthy drug development timeline, in which it typically takes 10 to 12 years for a promising new medicine to secure FDA approval and reach patients, Makary said. Between the start of a phase 1 trial and the submission for approval, almost half of clinical development time is spent on paperwork, he said.
“Forty-five percent of the time is dead time,” Makary said. “Instead of teams actively conducting a clinical trial, investigators and staff are doing paperwork.”
Adoption of real-time trials would help the U.S. boost its competitiveness in the international biopharma arena, Makary added, and also help respond to future pandemics.
Stephanie Morain, Ph.D., a bioethicist at Johns Hopkins University who has sat on institutional review boards that scrutinize plans for human research, welcomes efforts to cut down on administrative burden.
“I will readily accede that there are plenty of ways where, administratively, we could be moving faster,” Morain told Fierce Biotech. “I remain enthusiastic for seeing efforts that are being made in good faith to speed the trial timelines.”
AstraZeneca’s real-time trial is the phase 2 Traverse trial, which is testing the company’s BTK inhibitor Calquence in combination with AbbVie’s Venclexta and rituximab (Rituxan) for treatment-naïve mantle cell lymphoma. The FDA said it has already received and validated data from the trial through software company Paradigm Health’s platform.
“This program is an important first step towards strengthening clinical trial data collection,” Amy McKee, oncology senior vice president at AstraZeneca, said today at an FDA press conference. “The ultimate goal is to move data as quickly as possible across this ecosystem to accelerate our ability to bring new therapies to patients to make a meaningful difference in their lives.”
Amgen, meanwhile, is conducting a phase 1b trial for its DLL3 T-cell engager, Imdelltra, which is currently in the final stages of site selection, the FDA said.
“The new approach is designed to sit alongside traditional approaches to doing clinical research and randomized studies,” Amgen Chief Medical Officer Paul Burton, M.D., Ph.D., said during the press conference. “The pilot program that we are doing with tarlatamab, our small-cell lung cancer medicine, really exemplifies this.”
Another part of the effort is a pilot program set to launch this summer, the FDA said, with the goal of finding ways to optimize early trials using AI. The agency is currently seeking public comments (PDF) on this plan.
“This is a logical next step from the FDA rather than a major step-change, and is an example of regulators doing what they should do by responding to a fast-moving technology and beginning to define a workable pathway for its use,” analysts from Evercore ISI wrote in an April 28 note about the proposed AI pilot.
The goal is to “scale this across the agency,” Mallika Mundkur, M.D., the FDA’s deputy chief medical officer, said during the press conference, “in a way that adds the greatest value for public health.”
During the call with reporters, Makary highlighted the potential for FDA staff to keep up with trials as they are happening and potentially make regulatory decisions without having to wait for the trial to conclude.
“When a patient develops a fever, FDA regulators can see that a patient is experiencing a fever as they have that symptom,” the commissioner said. “If a tumor shrinks, FDA regulators can see that there is a response to the drug as the CAT scan is being read by the radiologist.”
This real-time review is not meant to replace formal meetings between sponsors and the agency, FDA Chief AI Officer Jeremy Walsh said on the call with reporters, and it will be up to the reviewers themselves to decide how the information is used.
“We’ll let the review committees decide what type of engagement that they feel like they need to have in order to get the answer they need, in order to get to a regulatory decision,” he said.
What could go wrong?
Real-time access to trial data could present privacy concerns for patients, but Walsh was quick to dispel these worries.
“We’re not interested in seeing that patient-level data right now,” Walsh said on the call. “What we’re interested in is, can the FDA make a regulatory decision on signals? Can we see what’s actually happening to be able to move you from an early phase 1 to a phase 2 trial without having to reanalyze all the data?”
In today’s press conference, Makary reiterated that the purview of the FDA’s real-time review will be limited to safety and efficacy endpoints that are agreed upon in advance.
“Initially, we will take both the data submitted the routine way and the data that we’re able to see in real time,” the commissioner said. “We’ll reassess at the end of the pilot to see what we can do better.”
So long as data protection procedures are in place and effectively communicated to trial participants, Morain sees no cause for concern either.
“The patient privacy piece wouldn’t concern me, provided appropriate protections are in place,” Morain told Fierce. She added that studies have found that trial participants are overwhelmingly okay with their patient-level data being shared, though this again is not planned for real-time trials.
The bigger concern for Morain comes down to the balancing act between fast drug development and the assurance that a new drug is thoroughly vetted.
“Patients want earlier access to new therapies, but they have interest in those therapies being safe and effective,” Morain said. Additionally, if a middling new therapy makes it onto market due to speedy review, other companies will be less likely to pursue their own novel drugs in that space.
Any effort that can speed up drug development without compromising safety and efficacy is “a step forward,” Fred Ledley, M.D., a former biotech executive and director of the Center for Integration of Science and Industry at Bentley University in Massachusetts, told Fierce Biotech.
Ledley agreed that the tension between speed and quality of reviews is a concern with the new real-time trial program, as it also is for other efforts like accelerated approvals and adaptive clinical trials with interim analyses.
“It is good that the FDA is introducing this only as a pilot program,” Ledley said. “It is important to evaluate this concept in practice, not in theory.”
Makary likened the real-time clinical trial initiative to other efforts undertaken by the FDA under his leadership, all with the goal of hastening drug development. These past efforts have faced their fair share of criticism, however—the generative AI tool Elsa has been accused of hallucinating false information, while the Commissioner’s National Priority Voucher program has been hit with concerns about corruption.
Makary’s tenure has also been marked by extensive layoffs and concerns of political interference expressed by former high-level officials.
“For all of the anxiety people at FDA and others had when Makary was coming in,” Morain said, she had colleagues there whom she knows were excited about the chance to cut bureaucratic red tape.
“There were people who’ve been the FDA a long time who could point to systems that were put in place decades ago that don’t necessarily match the way technology is today and don’t match the way clinical trials are done,” Morain said. “There are certainly opportunities,” but “these are very large ships to turn.”
Editor’s note: This story was updated at 2:45 p.m. ET with information from a press conference.
