FDA ADVISERS TIED TO INDUSTRY
By Dennis
Cauchon
USA TODAY
09/25/00 - Updated 12:24 AM ET
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."
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NUMBER OF DRUG EXPERTS AVAILABLE IS LIMITED
By Dennis
Cauchon
USA TODAY
09/24/00 - Updated 11:56 PM ET
[SIDEBAR: 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."]
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 absorbedin 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
financialconflicts participate, but "it should be rare and
that person should not be allowed to vote."
Financial conflicts were most common when committees considered
broaderissues, 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 havebeen 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.
Any personal reports, thoughts or response on this?