Real-Time Trial Pilot Shows How Clinical Trial Data Reach FDA

The Food and Drug Administration said on April 28 that it has started receiving data in real time from two clinical trials, an early test of what it calls real-time clinical trials. In its announcement, the agency said AstraZeneca is running a Phase 2 trial, TRAVERSE, in previously untreated mantle cell lymphoma, with The University of Texas MD Anderson Cancer Center and the University of Pennsylvania taking part, and Amgen a Phase 1b trial, STREAM-SCLC, in limited-stage small cell lung cancer. FDA met each sponsor to set criteria for which signals would be reported in real time, and said it has received and validated signals from the AstraZeneca trial through Paradigm Health.

FDA also issued a request for information on a wider pilot, with comments due May 29. It said it intends to publish final selection criteria in July and pick participants in August.

How data travel now

FDA described the current model in one line: "Data is typically reported from sites to sponsors, who analyze and subsequently submit data to the FDA." Commissioner Marty Makary said key data signals "can take years to reach the FDA."

For drugs under an investigational new drug application, the timing of what FDA does see is set by regulation. Under 21 CFR 312.32, a sponsor must send FDA and all participating investigators an IND safety report on potential serious risks no later than 15 calendar days after determining that the information qualifies. That includes any suspected adverse reaction that is both serious and unexpected, with "suspected" meaning there is a reasonable possibility the drug caused the event. Unexpected fatal or life-threatening suspected adverse reactions carry a shorter clock: no later than 7 calendar days after the sponsor first receives the information.

The rest arrives more slowly. Under 21 CFR 312.33, a sponsor must submit a brief report on the progress of the investigation within 60 days of the anniversary of the date the IND took effect.

What real time would change

In the proof-of-concept setup, Paradigm Health's platform captures data from electronic health records and other sources, evaluates FDA-defined data points and reporting criteria as the trial runs, and sends only the signals needed for regulatory decisions to the sponsor and FDA at the same time, Clinical Research News reported. The outlet said the data are traceable and auditable and that the system minimizes the transfer of patient data.

FDA's stated aim goes beyond faster safety reporting. Most development happens in discrete phases, each run under its own protocol, with a hiatus between one phase and the next, the agency said. By letting FDA see key results as they accumulate, real-time trials could shorten or eliminate that gap, a step toward what it calls "continuous" trials.

The April 28 announcement describes proof-of-concept trials and a request for information on a pilot whose design is still open for comment. It does not amend the IND reporting regulations, so the 15-day and 7-day safety clocks and the annual reports remain the baseline for trials under an IND.