Medical Device Daily Washington Editor

WASHINGTON — Post-marketing surveillance of products by the FDA is clearly coming to the forefront as more and more drugs and devices are being either withdrawn or found to have serious risks, and it is becoming obvious that the agency does not have sufficient resources for thorough post-market review. And what happens in the drug sector soon seems to appear in the device arena.

A Senate hearing last week focused on the recent report from the Institute of Medicine (Washington) that charged that the FDA is failing in the application of science to drug approvals and post-market assessment. And this discussion was combined with an evaluation of S. 3807, which is titled “Building a 21st Century FDA: Proposals to Improve Drug Safety and Innovation,” also indicating the need for upgrading the agency’s work in its post-market surveillance function.

Suggesting that there may have been either parallel thinking or prepublication consultation in preparation of the two documents, committee chairman Mike Enzi (R-Wyoming) said that some of the recommendations in the IOM were “part of the bill before the IOM report” made it into publication.

Speaking on behalf of IOM, Sheila Burke, who co-chaired the institute’s panel that produced the report on the FDA, said that the recommendations constitute “a lifecycle approach” to drug evaluation — from initial regulatory filings to an understanding of effectiveness in the market place. She said that this is not a new concept, but a concept only “implemented in a limited and fragmented manner.”

Burke hinted that absolute product safety is unattainable, remarking that “delaying approval until absolute safety has been established” and pulling a drug at the first hint of problems “are simply not options.” Still, she argued that the culture at the agency’s Center for Drug Evaluation and Review “is at times dysfunctional,” blaming “turnover and instability at the commissioner’s office.” She said that the agency might be better served if the post was assigned for “a six-year fixed term.”

Enzi suggested that the FDA has its share of organizational unhappiness but noted that this may be “because we don’t have an FDA commissioner.”

As for getting Andrew von Eschenbach’s nomination through the Senate, Enzi said he hoped that “we’ll do that before we leave” for the December recess. He said that von Eschenbach “left a job he loves ... for a thankless job” at the FDA and called on the Senate to get past partisan bickering and put von Eschenbach in place.

Sen. Ted Kennedy (D-Massachusetts) noted that while the FDA sees to the health and safety of 300 million Americans, he suggested that recent events indicate that “the FDA itself needs treatment.” The former and future chair of the committee pointed out that the agency’s budget amounts to less than $6 per year for each American citizen.

User fees found no more welcoming an audience at IOM than at industry gatherings.

“A substantial and sustained financial effort is needed” to enable the FDA to roll out the recommendations in the IOM report or in the Enzi/Kennedy bill [S. 3807], but “we prefer that the additional funding ... come from appropriated funds,” Burke said.

As for the notion of creating a separate body to review drug safety, Burke said “we do not believe ...setting up a freestanding” office for drug safety is a sensible way to go about the task of beefing up post-market tracking “because it is inconsistent with the lifecycle approach” advocated by IOM. Burke also noted that the IOM believes the lifecycle approach involves tracking a drug until it is no longer being used.

As for the IOM’s allegations that the culture at the Center for Drug Evaluation and Research is broken, Burke said that legislation alone cannot fix the problem. But a panel of outside experts could foster an atmosphere more to the liking of the disgruntled at the FDA, she said.

Kennedy asked Burke how important it is to pass S. 3807.

She replied that it is “enormously important” but that the agency “is starved for resources.” She pointed to the adverse events reports system as an example of a function that collects quantities of data that the FDA is not staffed to fully analyze.

She made the case for inserting “safety staff earlier in the approval process.”

Burke also said that “the agency needs far greater clarity in its authority,” suggesting that one of the agency’s beefed-up powers should include the ability to “call unilaterally for changes in labeling.”

The IOM’s aversion to increased reliance on user fees is not absolute. Pharmaceutical user fees have made “an enormous and positive difference in bringing drugs to market,” Burke said, and that if the federal government cannot come up with additional monies for more extensive post-market tracking, user fees should fund the effort.

Sen. Hillary Clinton (D-New York) complained about what she saw as a culture that puts politics over science at the FDA, adding: “I believe strongly in comparative effectiveness studies.”

Clinton mentioned as an example that a recent study of the efficacy of COX-2 inhibitors demonstrated “no difference in efficacy ... compared to OTC pain-relieving drugs.”

Burke said that this consideration was not part of the IOM charge, but seconded the idea.

Diane Thompson, VP for public policy and communications at the Elizabeth Glaser Pediatric AIDS Foundation (Washington), said the foundation does not “believe that patients should have to choose between safety and speedy access” to lifesaving drugs. The foundation’s position on user fees veered from that of the IOM, however. “Safety-related performance goals must be added to PDUFA,” Thompson argued.

Thompson said also that the agency should track off-label use of drugs since roughly 20% of prescriptions are written for such uses, and urged that phase II clinical trial data should be made available along with phase III data.

The proposal to require publication of phase II trial data was seconded by Jim Guest, President/CEO of Consumers Union (Yonkers, New York), but the idea drew little interest among the committee members in attendance.