USA TODAY analyzed financial conflicts of interest
on the 18 expert advisory committees established by the Food
and Drug Administration's Center for Drug Evaluation and Research.
These committees vote on whether new drugs should be approved
and what regulations should govern the drug approval process.
The newspaper created a database of financial conflicts disclosed
at all 159 advisory committee meetings from Jan. 1, 1998,
through June 30, 2000. About 250 members appeared 1,620 times
during those meetings.
As required by law, FDA advisory committees disclose when
members have a financial interest in the subject of the meeting.
Financial interest is defined in FDA regulations "as
the potential for gain or loss as a result of government action
on a particular matter."
FDA Advisers Tied to Industry
By Dennis Cauchon, USA TODAY
More than half of the experts hired to advise the government
on the safety and effectiveness of medicine have financial
relationships with the pharmaceutical companies that will
be helped or hurt by their decisions, a USA TODAY study found.
These experts are hired to advise the Food and Drug Administration
on which medicines should be approved for sale, what the warning
labels should say and how studies of drugs should be designed.
The experts are supposed to be independent, but USA TODAY
found that 54% of the time, they have a direct financial interest
in the drug or topic they are asked to evaluate. These conflicts
include helping a pharmaceutical company develop a medicine,
then serving on an FDA advisory committee that judges the
drug.
The conflicts typically include stock ownership, consulting
fees or research grants.
Federal law generally prohibits the FDA from using experts
with financial conflicts of interest, but the FDA has waived
the restriction more than 800 times since 1998.
These pharmaceutical experts, about 300 on 18 advisory committees,
make decisions that affect the health of millions of Americans
and billions of dollars in drugs sales. With few exceptions,
the FDA follows the committees' advice.
The FDA reveals when financial conflicts exist, but it has
kept details secret since 1992, so it is not possible to determine
the amount of money or the drug company involved.
A USA TODAY analysis of financial conflicts at 159 FDA advisory
committee meetings from Jan. 1, 1998, through last June 30
found:
At 92% of the meetings, at least one member had a financial
conflict of interest.
At 55% of meetings, half or more of the FDA advisers had
conflicts of interest.
Conflicts were most frequent at the 57 meetings when broader
issues were discussed: 92% of members had conflicts.
At the 102 meetings dealing with the fate of a specific
drug, 33% of the experts had a financial conflict.
"The best experts for the FDA are often the best experts
to consult with industry," says FDA senior associate
commissioner Linda Suydam, who is in charge of waiving conflict-of-interest
restrictions.
But Larry Sasich of Public Citizen , an advocacy group,
says, "The industry has more influence on the process
than people realize."
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.
These
articles originally appeared in the USA TODAY September 25,
2000
|
