From MedPage Today:
FDA Touts New Adverse Reporting Rule
By John Gever, Senior Editor,
FDA officials took to the pages of the New England Journal of Medicine to highlight the agency's new system for reporting adverse events in clinical trials, which they hope will make such reports less numerous but more useful.
In an online Perspective article published Wednesday in the NEJM, Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, and other top CDER officials explain the rationale for the new regulation, which was announced in September 2010 and implemented this past March.
The new system shifts primary responsibility from individual investigators to trial sponsors for determining when adverse events seen in a clinical study are potentially related to the investigational drug, Woodcock and colleagues indicated.
At the same time, individual investigators will be required to report every adverse event to the trial sponsor.
Under the old system, sponsors were required to report to the FDA every individual adverse event that they knew about in a trial, irrespective of whether the trial drug may have been responsible.
But the individual investigators did not have to report every adverse event they saw to the sponsor. Instead, they were required to report only those events they believed were "probably" related to the trial drug.
This system misplaced the responsibility, because site investigators are in a relatively poor position to make such determinations, wrote Woodcock and colleagues.
"It's difficult ... for an investigator to attribute a serious adverse event to a drug on the basis of an isolated incident, and individual investigators often do not have timely access to the entire safety database," the officials argued.
Instead, they said, trial sponsors should be the ones to determine when adverse events are drug-related, and site investigators should report to the sponsors every serious adverse event they see.
"Causality of adverse events is best evaluated in the aggregate by the sponsor," according to the FDA officials.
Moreover, the only adverse event reports the agency wants to receive are those describing "serious, unexpected, suspected adverse reaction[s]," Woodcock and colleagues wrote. They suggested that episodes of Stevens-Johnson syndrome would likely qualify, since the condition is known to be associated with drug exposures and is highly unusual otherwise.
On the other hand, a stroke occurring in an elderly patient would not be unexpected and would seldom be a drug reaction.
The new regulation instructs sponsors not to report individual events like these that would be expected in the study population anyway, or that were prespecified endpoints in the trial.
In the past, the FDA received many such individual reports, and it could hardly ever make use of them.
"Large numbers of such uninterpretable single case reports can distract clinical investigators, the FDA, and IRBs from recognizing genuine drug-safety problems," Woodcock and colleagues wrote.
"The FDA expects that this new approach will reduce reporting-data noise that may mask true signals of significant adverse events, so that what is reported to the FDA, clinical investigators, and IRBs will be more meaningful and relevant to patients' safety," the officials wrote.
They added that trial sponsors are still expected to monitor and report nonserious adverse events as they have done in the past.
When sponsors do become aware of serious and unexpected events in a trial, the regulations give them 15 days to inform the FDA -- or seven days if an event is fatal.
