23 mars, 2007 10:50

Improving Drug Safety -- we're in the news!

One of our concerns has been the misuse of FDA advisory committees. The committees are intended to provide "outside, independent expertise" on controversial approval decisions, but we conducted a study that found that they are usually "yes men" who recommend approval even when they doubt that the product is proven safe or effective.

The Food and Drug Administration said yesterday that it plans to make extensive changes in how it selects medical experts to serve on its advisory panels after years of complaints that many of them have financial ties to the companies whose products they evaluate.

The proposal would eliminate many experts who serve on the panels despite having such financial conflicts, FDA officials said. Experts with limited conflicts of interest would be allowed to participate in the discussions but not to vote on the recommendations made to the agency.

The advisory committees play a central role in regulating drugs, medical devices and diagnostic tests. Their decisions largely determine what drugs and medical products can be marketed to Americans -- because the agency nearly always follows the panels' guidance.

In recent years, concern about the composition of the panels has reached a crescendo. The FDA and others have argued that overly strict rules might eliminate many -- in some cases all -- of the panel candidates with the needed expertise.

Yesterday, officials maintained that the agency's procedures have not been biased in favor of industry, but the new guidelines implicitly acknowledge what critics have long said -- that it is possible to find enough qualified experts who do not have ties to drug and device manufacturers.

"This is one of several announcements the FDA has made in recent months whose timing suggests they are reactions both to the IOM report and the bills moving through Congress," said R. Alta Charo, a University of Wisconsin bioethicist who served on the institute's FDA review panel.

"The FDA is intent on getting out ahead of some of its critics as effectively as possible -- and that is a good thing," she said. Although the changes have not gone as far as urged -- capping the number of members with conflicts on any given panel -- Charo said: "The last thing I want to do is discourage incremental progress."

Under the new rules, any scientist or physician who has had $50,000 or more in financial ties to a company over the past 12 months, including stock or consulting arrangements, would be barred from panels evaluating that company's products. Those who have received less than $50,000 in the previous year might be allowed to participate in the discussion but could not vote.

In general, the FDA said, it will try to limit the participation of experts who are perceived to have a conflict of interest. If the FDA commissioner thinks an expert with financial conflicts is needed on a given panel, an exception can be made, but this will be rare, said Randall Lutter, the agency's acting deputy commissioner for policy.

Lutter and Jill Hartzler Warner, senior policy adviser and counselor in the FDA's Office of Policy and Planning, said it is not possible to say precisely how many experts who currently serve on advisory panels would be affected by the new rule, but they said it would have a significant impact. Agency officials did calculations to measure the impact of various cutoff points before deciding on $50,000.

"We are very interested in ensuring we have the best possible access to scientific experts," Lutter said. "At the same time, we seek to ensure we have the fullest public confidence in the integrity of our advisory committee process."

Lutter denied that the proposal, which will be open for public comment for 60 days, reflects FDA unease about the panels. Rather, he said, the step was being taken to ensure that the public's perception about the advisory panels' quality is in line with the agency's perception.

"We think we have done a very good job of ensuring the process deserves the respect of the American public," he said. "We are not aware of any instances where decisions have been unfairly or adversely affected by conflicts."

Lutter and Warner said the $50,000 figure would not apply to research grants made by pharmaceutical companies to universities where the scientists work, only to grants given directly to experts.

"A drug rep who takes someone to a memorable restaurant twice a year to chat about their research is spending relatively little money but is building a relationship that is likely to be more influential than giving a $2,000 honorarium -- perhaps even more than a $50,000 grant for a study funded by several companies," she said.

Zuckerman's center analyzed the votes of 11 FDA advisory committees from 1998 through 2005. She said the idea that experts with conflicts could serve on committees but not vote was not well thought out -- because nonvoting members play a substantial role in pushing the committees in one direction or another.

"Our study of advisory committee deliberations showed the collegial, consensus-building nature of these decisions," she said. "The votes are often unanimous because the group comes to a consensus, almost always to approve a product."

--------------------------

By Ricardo Alonso-Zaldivar

Los Angeles Times

March 22, 2007

The Food and Drug Administration said Wednesday that it would bar outside medical experts with a financial interest in a manufacturer from voting on advisory panels assessing whether drugs or other products made by that company are safe and effective.

The proposed restrictions -- which would also apply to experts with ties to competing firms -- would significantly strengthen the FDA's conflict-of-interest policy. One recent study suggests that more than one-fourth of FDA advisors may be prohibited from voting.

Industry supporters reacted cautiously to the announcement, saying it may limit the pool of qualified advisors the FDA can draw on. Consumer groups welcomed the move, although some said the proposed policy came with a considerable loophole.

That's because the FDA would still permit experts with as much as $50,000 in financial ties to manufacturers to participate on panels as nonvoting advisors, giving them an opening to sway those voting.

FDA officials said the agency was tightening its rules as part of a broader effort to regain the public's trust.

The withdrawal of the painkiller Vioxx and revelations about the suicide risks of antidepressants, along with other safety problems, have tarnished the FDA's image. A September report from the Institute of Medicine of the National Academies called on the FDA to adopt stronger policies to minimize conflicts of interest among advisory panel members.

Critics have accused the agency of becoming too cozy with industry, and Congress is working on legislation to strengthen the FDA's safety program.

Dozens of advisory committees guide much of the FDA's decision-making on drugs and other products. Panel members -- usually prominent physicians and academic researchers -- vote on issues such as whether risky medications should be taken off the market, or what information should be provided to patients and doctors.

The FDA generally follows the recommendations of the panels, which also may include nonvoting members representing consumers and industry.

The financial ties to be examined under the guidelines include individual research grants, contracts and consulting fees, and investments in company stock, the FDA said. The agency will look at conflicts in the year before an advisory panel meets.

"The major achievement here is that you cannot vote on an advisory panel if you have a conflict of interest," said Rep. Maurice D. Hinchey (D-N.Y.), who has been a sharp critic of the agency. "It's not perfect, it's not the end of the road -- but it is a step in the right direction."

But Diana Zuckerman, president of the National Research Center for Women & Families, said a $50,000 exemption was too generous.

"Think of all the members of Congress who have gotten into trouble for much less," she said. "People do crazy things for a lot less than $50,000 -- including people who earn a lot of money."

The new restrictions will take effect after a 60-day period for public comment.

Current FDA rules automatically bar outside experts from taking part in an advisory panel meeting if their investments in a company likely to be affected by the decision exceed $100,000 or account for at least 15% of their net worth. Those with smaller investments may take part, but must file a disclosure form. Such conflicts are routinely noted in an FDA statement at the start of each meeting.

The current policy allows many experts with consulting contracts or other financial ties to manufacturers to fully participate in advisory committee meetings that involve products made by the specific firms.

A study published last year in the Journal of the American Medical Assn. found that 28% of committee members disclosed financial conflicts, but only 1% recused themselves from voting under current rules.

FDA officials said they could not reliably estimate how many current advisors would be disqualified under the new policy.

"One of the difficulties in trying to come up with that exact number is that it's meeting-specific," said Jill Hartzler Warner, an FDA lawyer. "You have to know [in advance] the meeting topic." But officials said the agency would step up its efforts to recruit panel members without any conflicts.

The JAMA study found only a weak link between the participation of members with conflicts and the outcome of meetings. In a majority of cases, excluding the advisors with conflicts would have reduced the margin of approval for the drug that was being considered, but it would not have changed the final outcome.

"We think we have already done a good job" keeping FDA decisions free of any conflict, said Randall Lutter, acting deputy commissioner for policy. But he acknowledged that current conflict-of-interest rules had been unevenly applied across different advisory panels.

"We are committed to making the process even stronger and better-understood," Lutter said. The new policy will increase "consistency, predictability and transparency," he added.

But FDA officials would not say exactly how they arrived at the $50,000 figure as the threshold for financial conflicts.

Lutter said the threshold struck "an appropriate balance" between allowing the FDA to tap the expertise of academic scientists involved in industry-funded research and the need to reassure the public that the agency's decision-making process was sound.

Independent experts close to the pharmaceutical industry said the new policy appeared to mark a change in direction for the agency.

"I am surprised the FDA is doing this," said economist John E. Calfee of the American Enterprise Institute. "It's a more activist FDA than I would have expected."

Hinchey, the New York congressman, said newly confirmed FDA Commissioner Andrew C. von Eschenbach was making a concerted effort to respond to problems that critics had identified.

But Dr. Peter Lurie, author of last year's JAMA study that revealed the extent of FDA conflicts, said financial interests were not the only source of potential bias. Doctors treating patients in clinical practice, he said, are often more likely to approve a drug than are medical researchers, who focus on statistics.

"Conflict-of-interest guidelines are important, but they don't solve all the ills," said Lurie, deputy director of Public Citizen's Health Research Group, a consumer advocacy organization. "There's an inordinate focus on clinicians and an insufficient focus on statisticians and epidemiologists, who tend to look at the data in a more dispassionate way. The clinicians always want more toys."

By Catherine Larkin

March 21 (Bloomberg) -- The U.S. Food and Drug Administration proposed stricter rules to limit the role of outside advisers with financial ties to the industries it regulates.

Advisory committee members with financial conflicts wouldn't be allowed to vote on recommendations to the regulatory agency under the proposal made public today. Panelists who received $50,000 or less in the previous year from a company with an interest in a matter before the committee could get waivers to participate without voting.

The new rules replace an array of policies used to select committees. Lawmakers and consumer groups have criticized the agency for allowing experts with industry ties to serve on the panels. Some called the proposal a step forward.

``I'm very happy about it,'' said Representative Maurice Hinchey, a New York Democrat, in a telephone interview today. ``This is something that has created a lot of danger by having people make decisions when they are likely to make them in their own financial interests rather than in the public interest.''

Committee members are paid to meet several times a year to recommend approval, rejection or further research on drugs, medical devices and biological products. The FDA usually follows the advice of its advisers, though it isn't required to do so.

`Significant Number'

The FDA doesn't know how many committee members would be affected by the new rules, though it probably would be a ``significant number,'' said Randall Lutter, the agency's acting deputy commissioner for policy, in a conference call.

Disqualifying financial ties under the new rules include stock, consulting fees, contracts, personal grants or other benefits received from a drugmaker whose medicine, or a competing product, is being considered by the committee. Research grants to a university employing an advisory panel member wouldn't be counted.

Panelists With Ties

More than a fourth of the panelists and consultants on FDA advisory panels had financial ties to a drugmaker whose product was being considered or to a competitor, according to a study by the Public Citizen consumer group that appeared in the April 26 edition of the Journal of the American Medical Association.

The FDA's Lutter said he's not aware of any cases in which advisers' financial ties ``unfairly or inappropriately'' affected the outcome in a committee.

Under the new policy, waivers may be given to panelists who received less than $50,000 if they have unique qualifications or if it's difficult to find experts without financial ties. The FDA commissioner could also allow committee members with interests exceeding $50,000 to participate ``in exceptional instances,'' Lutter said.

One consumer advocacy group said the waivers leave a ``giant loophole.''

``Everybody is going to know that guy is sitting there, but he can't vote,'' Lurie said in a telephone interview. ``It's going to, in effect, create tiers within the advisory committee: those who can vote and those who cannot.''

The public will have 60 days to comment on the FDA's proposal after it is published in the Federal Register on March 23.

A Cleaner Food and Drug Agency

Some patient advocates believe the $50,000 exclusion is too generous, and the agency needs to explain more fully how it decided that was the proper cutoff point. It also needs to address whether nonvoting experts — those with smaller financial ties — might still unduly sway a committee’s decision.