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IOM Report Faults FDA Drug-Safety Process Print E-mail
Friday, 22 September 2006

A report by the Institute of Medicine is sharply critical of FDA's drug safety monitoring system: "The report’s conclusions are striking and often damning – particularly when discussing the agency’s Center for Drug Evaluation and Research, known as C.D.E.R." 

The report fully validates the concern expressed by critics of the agency who have watched in horror as thousands have suffered preventable harm while senior FDA officials at CDER have sacrificed safety for the sake of expediency-- pretending not to notice, serving as the drug industry's guardians.

 "The Institute described an agency split by fierce disagreements that have not been resolved by repeated reorganizations and management efforts. Indeed, managers’ failure to address such disagreements competently “has played an important role in damaging the credibility” of the F.D.A.."

The IOM panel made important recommendations that would put the agency back on track to fulfill its mission of protecting the public health instead of industry's cash flow:

•  Put a symbol on the packages of new drugs to denote that the medicine's benefits and risks may not be fully understood. It would remain in     pace  for two years.
•  Ban advertising directed at patients during that two-year period.
•  Review the risks and benefits of all new drugs after five years.
•  Bolster the Food and Drug Administration's safety staff and give it an integral role in drug approval.
•  Give FDA legal authority to order drug companies to conduct safety studies and to institute other precautions to protect patients.
•  Modernize and extend the FDA's databases for tracking serious reactions to prescription drugs.
•  Create an Internet registry to post results of clinical drug trials.
•  Adopt stronger policies to minimize conflicts of interest among outside advisors who serve on the panels that guide much of the FDA's   work.
•  Establish a six-year term for the FDA commissioner, who now serves at the pleasure of the president, to provide stable leadership.

Grdiner Harris notes: "Couched in formal language and careful footnotes, the report’s boring exterior belies an incendiary heart. With each page, it paints a devastating picture of a dysfunctional agency that is unable to ensure the safety of the nation’s drug supply."
 
The report is available at: http://www.iom.edu/ CMS/3793/26341/37329.aspx
 
Contact: Vera Hassner Sharav
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http:// www.nytimes.com/2006/09/22/business/22fdacnd.html  
 THE NEW YORK TIMES
September 22, 2006
Report Lists Faults of F.D.A. Drug-Safety Process
By GARDINER HARRIS

WASHINGTON, Sept. 22 — The nation’s system for approving and monitoring the safety of medicines is inadequate and needs far-reaching reforms, and the Food and Drug Administration  is plagued with poor management and persistent internal squabbling, according to a long-anticipated study of the agency.
The report by the Institute of Medicine is likely to intensify a debate about the safety of the nation’s drug supply and the adequacy of the F.D.A.’s oversight. The debate began in earnest in September 2004 when Merck  withdrew its popular arthritis drug, Vioxx.

The Institute of Medicine, a nonprofit organization created by Congress to advise the federal government on health issues, conducted the study at the request of the F.D.A.
Susan Bro, an F.D.A. spokeswoman, said that the agency appreciated the work of the institute. “While we have done a lot of work over the past two years to improve the drug-safety enterprise at F.D.A., we recognize that work still remains to be done,” she said.
Citing the Vioxx withdrawal, which happened when long-term studies revealed risks to patients five years after the drug was approved, several prominent senators have already proposed significant reforms of the F.D.A., some of which the report seems to endorse.

The report’s conclusions are striking and often damning – particularly when discussing the agency’s Center for Drug Evaluation and Research, known as C.D.E.R.
“Every organization has its share of dysfunctions, unhappy staff members and internal disputes, but the committee came away from various encounters with C.D.E.R staff and management with a deep concern about C.D.E.R.’s organizational health,” the report said.

The report made these recommendations, most of which would require Congressional authorization:

 ¶ Drugs should only be approved for five-year periods so that the F.D.A. can thoroughly review post-approval safety questions.
¶ Newly-approved drugs should display a black triangle on their labels to warn consumers that their safety is more uncertain than that of older drugs.
¶ Drug advertisements should be banned during this initial period.
¶ The F.D.A. should be given the authority to issue fines, injunctions and withdrawals when drug makers fail -- as they often do -- to complete required safety studies.
¶ The F.D.A. commissioner should be appointed to a six-year term.

The Institute described an agency split by fierce disagreements that have note been resolved by repeated reorganizations and management efforts. Indeed, managers’ failure to address such disagreements competently “has played an important role in damaging the credibility” of the F.D.A., the report said.

Critics of the F.D.A. have long been divided into two, warring camps. Some say the agency fails to approve life-saving medicines quickly enough, while others complain that it is so intent on rapid approvals that it fails to ensure the safety of the drugs.

The Institute’s report champions the latter view by calling for greater caution. It suggests that one of the F.D.A.’s biggest problems is a deal struck in 1992 between Congress and the drug industry in which drug makers agreed to pay millions in fees in order to speed reviews.

This deal has increased pressures on drug reviewers to act quickly and it has limited “the ability of reviewers to examine safety signals as thoroughly as they might like,” the report said.
“Some also have serious concerns that the regulator has been ‘captured’ by industry it regulates, that the agency is less willing to use the regulatory authority at its disposal,” the report said.

It criticizes the agency’s regulatory tools as “all-or-nothing.”
“The agency needs a more nuanced set of tools to signal uncertainties, to reduce advertising that drives rapid uptake of new drugs, or to compel additional studies in the actual patient populations who take the drug after its approval,” the report states.

Couched in formal language and careful footnotes, the report’s boring exterior belies an incendiary heart. With each page, it paints a devastating picture of a dysfunctional agency that is unable to ensure the safety of the nation’s drug supply.

The report will almost certainly bolster efforts by some in Congress to pass fundamental reforms.

Sen. Michael B. Enzi, Republican of Wyoming and chairman of the Health, Education, Labor and Pensions Committee, and Sen. Edward M. Kennedy   of Massachusetts, the ranking Democrat on the committee, have jointly proposed a bill that would undertake at least some of the reforms advocated by the report.

Another bill sponsored by Sen. Charles Senator Charles E. Grassley , Republican of Iowa and chairman of the Senate Finance Committee, and Senator Christopher J. Dodd , Democrat of Connecticut, offers similar proposals. There is little chance that Congress will act on any of these proposals before next year, when it must reauthorize the 1992 funding deal with the drug industry. Negotiations between the drug industry and F.D.A. about the parameters of that deal are already under way.

Despite its fierce criticisms, the report may bolster the confirmation prospects of Dr. Andrew von Eschenbach, who is presently the agency’s acting commissioner. A senate committee approved Dr. von Eschenbach’s nomination on Wednesday, but two Republican senators have vowed to block it.

Over the past 10 years, no commissioner has served more than two years. The report decried this “lack of stable leadership.”
“Without stable leadership strongly and visibly committed to drug safety, all other efforts to improve the effectiveness of the agency or position it effectively for the future will be seriously, if not fatally, compromised,” the report states.

The report recommends that the commissioner be nominated for a six-year term, but such a change may not solve the problem of early exits. President Bush has nominated two previous commissioners. The first left for another job within the administration; the second left amid allegations of financial improprieties.
The report recommends that Michael O. Leavitt, the secretary of health and human services, appoint an independent board to advise the agency’s commissioner “to implement and sustain the changes necessary to transform” the agency’s culture.

The report rejects suggestions made by Mr. Grassley and others that the F.D.A. create a center for drug safety charged with monitoring the safety of drugs after approval.
“Achieving a balanced approach to the assessment of risks and benefits would be greatly complicated, or even compromised, if two separate organizations were working in isolation from one another,” the report concludes.

The F.D.A. asked the Institute of Medicine to review its drug safety system shortly after the Vioxx withdrawal in 2004. The agency has agreed to pay $3 million for the study.
Copyright 2006 .The New York Times Company <http://www.nytco.com/>

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http://www.latimes.com/news/nationworld/nation/la-na-fda23sep23,0,3587507.story?coll=la-home-headlines
THE LOS ANGELES TIMES
Drug Safety Overhaul Is Urged
The FDA spends far more time on approvals than on follow-ups, a review finds. Calls for reform include warning labels and limits on ads.
By Ricardo Alonso-Zaldivar and Denise Gellene

September 23, 2006

WASHINGTON — The government's drug safety system is seriously out of balance, devoting too much attention to approving new medications and not enough follow-up to uncovering risky side effects, a blue-ribbon scientific panel concluded in a major report released Friday.

Convened at the request of the Food and Drug Administration after a popular painkiller was linked to heart attacks, the experts in medicine, pharmacology, law and other fields issued a sweeping call for reform. Its 25 recommendations include establishing a fixed term for the FDA commissioner, restricting ubiquitous drug commercials and placing a special cautionary symbol on the packaging of newly approved medications.

The panel found "an imbalance in the regulatory attention and the resources available before and after approval" of new drugs, said Chairwoman Sheila Burke, a former Republican Senate staffer who now is chief operating officer of the Smithsonian. "Staff and resources devoted to pre-approval are substantially greater than those available post-approval."

The panel urged greater legal authority for FDA regulators to compel drug companies to carry out safety monitoring and called for significant increases in agency funding — although it failed to spell out exactly how much and where it would come from.

Consumer groups and advocates of overhauling the FDA hailed the report, while the drug industry issued a cautionary reaction. "Though there is always room for improvements, it would be a mistake to accept the notion that the FDA drug safety system is seriously flawed," Caroline Loew, vice president of the Pharmaceutical Research and Manufacturers of America, said in a statement.

The recommendations will frame a legislative debate over the future of the FDA, expected to be joined in earnest next year when Congress must renew user-fee legislation that provides much of the agency's funding.

The 15-member panel operated under the auspices of the Institute of Medicine, part of the National Academy of Sciences, which provides scientific advice to the government.

The FDA requested the review after the sudden withdrawal of Vioxx in 2004 generated a firestorm of criticism over its drug safety program. The widely used drug was pulled from the market by manufacturer Merck & Co. after a company-sponsored study confirmed that patients taking Vioxx were more likely to suffer heart attacks than those who did not.

An FDA safety reviewer, Dr. David Graham, had reached the same conclusion months earlier, only to have his warnings dismissed by superiors.

FDA officials on Friday were guarded in their reaction to the report. While praising the panel's effort, Acting Commissioner Andrew C. von Eschenbach said it would take time to review the findings. "We are at a point where we are assessing and analyzing the report," he said. "We are very committed to an effort of continuous improvement."

The head of the agency's drug review center expressed disappointment that the report focused closely on infighting between the scientists who evaluate new medications and those who monitor their safety after approval.

"I don't think there is any question that there are some cultural issues in the center," said Dr. Steven K. Galson, director of the Center for Drug Evaluation and Research. "What the report doesn't do really well is explain that the vast majority of the interactions within the center are very successful."

A previous investigation by the congressional Government Accountability Office had also concluded that the center's powerful new drugs branch — which gets the lion's share of funding and staff — treated the safety office as a sort of bureaucratic stepchild. Some FDA officials complained the new report did not take sufficient note of what it called two years of internal efforts to improve communication, both within the agency and with doctors and patients.

Graham, the FDA's most well known whistle-blower, saw vindication in the findings, although he said the recommendations did not go far enough. "The language is amazingly harsh," Graham said of the report. "This … was written by academicians by consensus, and to have strong language come through as it does means things are terribly, terribly bad at the FDA."

The report did not mince words:

"The committee found that the drug safety system is impaired by the following factors: serious resource constraints that weaken the quality and quantity of the science that is brought to bear on drug safety; an organizational culture that is not optimally functional; and unclear and insufficient regulatory authorities, particularly with respect to enforcement."

Although some leading reformers — including Graham — advocate the creation of an independent safety center within the FDA, the panel took another approach. It urged that a beefed-up safety office should work closely with the new drugs office in reviewing medications and, more important, in tracking potential problems after approval.

"A drug tested on a few hundred or a thousand people is much different when it is being used by millions over a long period of time," said Burke, the panel chairwoman. "Approval does not signify the end of uncertainty about a drug, and continued monitoring is necessary after approval."

To drive that point home to patients, the panel urged that newly approved drugs bear a special symbol — such as a black triangle — for the first two years after approval, as a reminder that their benefits and risks may not be fully understood. It also recommended a moratorium on advertising directly to patients during that period.

The panel also called on Congress to give the FDA specific legal authority to compel drug companies to carry out safety studies of approved drugs and to establish programs that would work with doctors and patients to mitigate risks. The agency currently must negotiate such steps with manufacturers.

The report's recommendation to closely integrate the work of FDA drug evaluators and safety reviewers tracks a proposal put forward over the summer in legislation by Sens. Michael B. Enzi (R-Wyo.) and Edward M. Kennedy (D-Mass.). That bill could emerge as the leading congressional proposal for FDA reform.

Another leading advocate of FDA reform, Sen. Charles E. Grassley (R-Iowa), called on President Bush to adopt the report as a blueprint to overhaul the agency. "Mr. President, the … report is an opportunity to finally address the criticisms lodged against the FDA over the last few years," Grassley said in a letter delivered to the White House.

But some academic experts worried that the report's recommendations, if followed to the letter, could have a chilling effect on drug approvals. Dr. Raymond L. Woosley, president of the Critical Path Institute, a nonprofit that works with the FDA and industry to streamline drug development, said the committee should have also addressed the question of bottlenecks in developing drugs for diseases such as Alzheimer's.

"Many of the things in the report are right on target, but they do not address the broader question of the role of the FDA in getting better healthcare from science," he said.

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Alonso-Zaldivar reported from Washington and Gellene from Los Angeles.

(INFOBOX BELOW)

Findings of FDA review

Here are some of the major recommendations of the Institute of Medicine report on reforming the nation's drug safety system:

•  Put a symbol on the packages of new drugs to denote that the medicine's benefits and risks may not be fully understood. It would remain in place for two years.

•  Ban advertising directed at patients during that two-year period.

•  Review the risks and benefits of all new drugs after five years.

•  Bolster the Food and Drug Administration's safety staff and give it an integral role in drug approval.

•  Give FDA legal authority to order drug companies to conduct safety studies and to institute other precautions to protect patients.

•  Modernize and extend the FDA's databases for tracking serious reactions to prescription drugs.

•  Create an Internet registry to post results of clinical drug trials.

•  Adopt stronger policies to minimize conflicts of interest among outside advisors who serve on the panels that guide much of the FDA's work.

•  Establish a six-year term for the FDA commissioner, who now serves at the pleasure of the president, to provide stable leadership.

Source: Institute of Medicine report
Copyright 2006 Los Angeles

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