Friday, September 22, 2006

http://www.nytimes.com/2006/09/22/business/22fdacnd.html?hp&ex=1158984000&en=0c27c1350fcf4c8b&ei=5094&partner=homepage
September 22, 2006

Report Lists Faults of F.D.A. Drug-Safety Process

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.


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