ROCKVILLE, MD—“One of the things the public has problems dealing with is uncertainty and building science around that uncertainty,” declared Jesse Goodman, MD, FDA’s science chief, at a recent meeting of the FDA Science Board. “We’ve seen a lot of things where people look at numbers based on bad data and because the numbers tell them something, they believe them.”

With the goal of applying the best science possible to a world of uncertainty, particularly the world of post-marketing drug surveillance, CDER has charged members of FDA’s Science Board with conducting a review of the agency’s pharmacovigilance programs, a function of the agency’s Center for Drug Evaluation and Review. Board members were asked to look at data sources for adverse event reporting, how those reports were submitted, and how they are processed and analyzed.

“How do we build science around the uncertainty of the findings,” Goodman asked the Science Board members. “We all recognize they’re uncertain, but how do we begin to define that in a much more rigorous way?”

One of the leaders of this review, Stephen Spielberg, MD, said that the group is in the very initial stages of the process and are still considering which issues deserve the most scrutiny. However, he and other board members have arranged discussions with people in FDA, starting with those who receive reports, then working to those that process the reports, and later moving on to FDA employees who analyze the reports.

One area of interest is adverse event reporting, and the group is hoping to determine what kind is most helpful. Are event reports from networks that capture a specific cohort of patients, such as the Pediatric Oncology Network, better sources of data than spontaneous reporting from individual physicians?

Spielberg described sample adverse event reports received from CDER, both on the liver toxicity of a certain drug. One was from a physician and the other was from a drug-induced liver injury network. The first was lacking entirely in detail. It did not even include the sex or age of the patient. The second included data that was exhaustive. “We’ll be talking about how to improve data sources. And we’ll probably go back to discussion of physician education and their responsibility to report potential adverse reaction and their responsibility to provide clinically useful information.”

Another area the group will be reviewing is in the examination of reports and separating out the pure positives from the false ones. “There’s a huge complexity in this. There are issues that range from what kind of analysis do you use, to how you manage the signal you detect, and how do you understand if there’s a public health facet to it.”

The group is planning on-site evaluations in October, with a full report due in February. “At most, we’re going to be able to lay out some areas for continued collaboration and interaction,” Spielberg said. “Hopefully we’ll get an understanding of how this process works and have some good recommendations on how to improve the process.”

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