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

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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.

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. B. Enzi, Republican of Wyoming and chairman of the Health,

Education, Labor and Pensions Committee, and Sen. 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. Senator E. Grassley, Republican

of Iowa and chairman of the Senate Finance Committee, and Senator 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. 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 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.