More FDA stuff::
From USA Today
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Number of drug experts available is limited
By Dennis Cauchon, USA TODAY
In October, pharmaceutical giant Johnson & Johnson sent a team of executives
to a Holiday Inn ballroom in Silver Spring, Md.
Their job: persuade the Food and Drug Administration's panel of independent
experts that an expensive antibiotic, Levaquin, should be the first drug approved
to treat penicillin-resistant pneumonia.
For Johnson & Johnson executives, the
FDA's Anti-Infective Drug Advisory
Committee included some familiar faces. At
least two of the experts were paid
consultants to the drug company and had
worked on the very same medicine that
they were being asked to evaluate for
approval in an important new market.
The expert panel's "consumer
representative," whose assignment is to
defend consumers' interests, had the most
extensive financial relationship with Johnson
& Johnson. Keith Rodvold, a pharmacy
professor at the University of
Illinois-Chicago, serves on a company
anti-infective drug advisory board, according
to Johnson & Johnson spokesman Marc
Monseau. Rodvold advised the company on
how to design and analyze the clinical trials
that got the drug approved. In 1999, he
designed a study to measure how Levaquin is absorbed in the lungs. The
company also uses him regularly as an consultant on a variety of issues,
Monseau says.
Rodvold declined to discuss his relationship with Johnson & Johnson and his
work on Levaquin. The company declined to say how much Rodvold had been
paid during the five years he has consulted for it.
The case of Levaquin reveals how deeply pharmaceutical industry money and
influence penetrates the drug approval process. FDA advisory committees
consist almost entirely of pharmaceutical industry consultants and
researchers. Even consumers' and patients' representatives on the committees
often receive drug company money.
At least one committee member had a financial stake in the topic under review
at 146 of 159 FDA advisory committee meetings, according to a USA TODAY
study of advisory committee meetings held from Jan. 1, 1998, through June 30,
2000. At 88 of those meetings, at least half the advisory committee members
had financial interests in the topic being evaluated.
Powerful panels
Eighteen FDA advisory committees play a crucial role in nearly every major
decision on drug regulation. They help decide what drugs should be approved
and how the pharmaceutical industry should be regulated. In recent years, the
FDA has followed every advisory committee recommendation to approve or
reject a medicine - except once, FDA spokeswoman Susan Cruzan says. (The
FDA approved the flu drug Relenza in July 1999 despite an advisory committee
voting 13-4 against approval.)
Investors follow advisory committees closely. A committee vote can add or
subtract hundreds of millions of dollars from a drug company's stock market
value.
The FDA is required by law to screen all committee members for financial
conflicts. The law says members have conflicts when committee action could
have the "direct and predictable effect" of causing the member a financial gain
or loss. The federal agency is forbidden from using experts with financial
conflicts unless a waiver is granted, usually on the grounds that the experts'
value outweighs the seriousness of the conflict. The FDA grants these waivers
routinely.
In the period analyzed by USA TODAY, the FDA granted 803 conflict-of-interest
waivers. Seventy-one other times, members had financial conflicts that were
voluntarily disclosed but did not require a waiver. In the 746 other member
appearances on the committees, there was no conflict of interest.
The FDA says granting waivers lets it tap the nation's leading researchers,
most of whom do work for the pharmaceutical industry.
"The system is designed to bring together the best scientific experts we can
find," says FDA associate commissioner Linda Suydam, who approves
waivers.
She says conflict-of-interest waivers go through as many as eight levels of
review before they are granted. But Larry Sasich, a pharmacist who works for
the Ralph Nader-founded Public Citizen's Health Research Group, says, "It is
outrageous that the pharmaceutical industry's influence is so great that even
some consumer representatives are on drug companies' payrolls."
Sasich says it might sometimes make sense to let experts with financial
conflicts participate, but "it should be rare and that person should not be
allowed to vote."
Financial conflicts were most common when committees considered broader
issues, such as warnings labels for pregnant women or how cancer studies
should be designed. At the 57 meetings on regulatory policy, committee
members had conflicts 91% of the time.
At the 102 meetings involving specific drugs, 33% of committee members had
a direct financial stake in the outcome.
It is impossible to determine how advisory committee decisions might have
been influenced by the financial relationships its members have. The FDA
stopped making details of financial conflicts public in 1992, after controversies
about whether the financial interests of committee members had biased
decisions on breast implants, Prozac and a drug to treat Alzheimer's disease.
The FDA says it stopped releasing details on conflicts because of concerns
about violating the privacy rights of committee members, not because of the
controversies.
Types of conflicts
Financial conflicts include stock ownership, consulting fees, research grants, a
spouse's employment and payments for speeches and travel. The conflict could
be a tie to the company whose drug is under consideration or to a company
that sells a competing drug.
Many financial conflicts are considered too small to require disclosure or a
waiver and were not counted in USA TODAY's study. For example, a
committee member can be paid up to $50,000 a year by a drug company
without any financial conflict being disclosed if the work was on a topic other
than what the committee is evaluating, according to FDA guidelines.
Committee members also can own up to $5,000 in stock in the company
appearing before the committee.
Advisory committees include many of the nation's leading researchers. The pay
is not high considering the stature of many members: about $400 a day for
meetings, plus travel expenses, and nothing for work done outside a meeting.
However, the assignments are prestigious, and committee members, whose
terms last four years, are in heavy demand as industry consultants.
Conflicts are most common on the committees that consider heart drugs.
Forty-eight percent of experts had financial conflicts when considering the
worthiness of specific heart medicines.
"The greater degree of expertise, the greater the potential for conflicts," says
Milton Packer, chairman of the Cardiovascular and Renal Drugs Advisory
Committee.
Packer is a good example. He is a leading figure in cardiovascular research
and has helped pioneer the development of drugs to treat congestive heart
failure. Last year, he led an effort by 150 leading cardiac researchers to
establish consensus guidelines on how to treat congestive heart failure, which
is suffered by 5 million Americans.
But his work with pharmaceutical companies creates many financial conflicts.
The FDA granted him a waiver that allowed him to participate in a meeting May
2 on the drug Refludan, which treats clotting. (Packer says he doesn't recall
what the conflict was.) And Packer did not participate in a meeting May 1 on
the heart drug Altace because of a financial conflict. (He declines to say what
the conflict was.)
Packer says consolidation in the pharmaceutical industry has increased the
potential for conflicts because there are fewer companies and nearly all have
heart drugs.
Financial conflicts are so common that eight of 10 members who evaluated the
drug Aggrastat, made by Merck, had conflicts of interest.
Packer says he doesn't believe that financial conflicts distort the
recommendations of advisory committees: " There are so many checks and
balances, it would be almost impossible for a single individual to steer the
committee."
At the meeting on October 20, 1999, on Levaquin, the chairman of the
committee and one other member stepped aside because of financial conflicts.
Of the 10 members remaining, four had received conflict-of-interest waivers from
the FDA.
In addition to Rodvold, New Jersey physician Carl Norden had consulted for
Johnson & Johnson in 1997 on the design of Levaquin studies for illnesses
other than the treatment of penicillin-resistant pneumonia, the company said.
Johnson & Johnson says having its consultants on the advisory committee
didn't create bias.
"We don't believe (advisory panel members) would let a consulting arrangement
compromise their reputation and stature in the medical community," says
Monseau, the Johnson & Johnson spokesman.
The advisory committee voted unanimously to recommend that Levaquin, an
$8-per-pill antibiotic, be approved for treatment of penicillin-resistant
pneumonia. The FDA ratified the decision in February. Levaquin has been on
the market since 1997, but the FDA's action allows Johnson & Johnson to
market the medicine as the first antibiotic approved for the more than 25% of
pneumonia cases that are resistant to penicillin.
Industry influence on advisory committees will increase later this year. As
required by a law approved in 1997, the FDA will add official industry
representatives to the committees. The industry officials will participate in
deliberations, but they will not be allowed to vote. |
