On September 30, 2004, in the biggest
recall ever of a prescription drug in the United States,
the blockbuster arthritis and pain medication rofecoxib
(Vioxx) was removed from the market when evidence emerged
that it doubled the risk for heart attack and stroke.
The recall comes on the heels of a
barrage of negative news about prescription medications.
First, there was the report from the Women's Health
Initiative that hormone replacement therapy (HRT)
increases the risk for stroke. (See Daily Health News,
August 24, 2004.) This was quickly followed by an ugly
controversy in which the US Food and Drug Administration
(FDA) tried to silence one of its own scientists from
exposing serious concerns about antidepressant use in
young people. (See Daily Health News, June 29, 2004.)
And now there is Vioxx. To learn
more about the Vioxx debacle and its broader implications
for drug safety, I spoke with Eric J. Topol, MD,
chairman of the department of cardiovascular medicine
at the Cleveland Clinic. Dr. Topol served on the FDA
advisory committee that originally approved Vioxx and
other painkilling COX-2 inhibitor drugs. He told me
that a congressional investigation already has been
launched into the effectiveness of FDA drug-safety
monitoring. This latest news is bound to intensify
that effort.
In the meantime, when it comes
to prescription drugs, there are steps that you
can take to protect yourself and your family...
QUESTIONS ABOUT SAFETY MONITORING
This blizzard of bad drug news
raises significant questions about the safety of
our medications. Is the FDA doing its job? Can you
trust the medicine your doctor prescribes? How much
influence do the pharmaceutical companies really
have? The history of Vioxx exposes a number of
very big holes in the pharmaceutical safety
system, such as...
A lack of follow-through.
As I have said before, the research presented
in support of new drugs does not necessarily tell
the whole story. There was early evidence showing
that COX-2 inhibitors could affect the heart.
However, in spite of the FDA advisory committee's
strong urging that the FDA require Vioxx manufacturer
Merck to conduct more rigorous studies, there was no
follow-through. To make matters worse, the most recent
studies that confirmed the connection were actually
testing Vioxx's impact on colon polyps -- and in
that study, Merck deliberately excluded people who had
heart disease. Meanwhile, the public assumes that this
approved drug was rigorously tested in a
scientifically pure way.
According to Dr. Topol,
the FDA could have and should have taken further
and more timely action, including demanding
additional clinical studies of people with heart
disease, as well as issuing earlier warnings
to the public.
Silence was golden. It turns
out that shortly before Merck voluntarily withdrew
Vioxx, FDA higher-ups "muzzled" investigator David
Graham, MD, associate director for science in the
FDA Drug Center's Office of Drug Safety. Poised to
report on the increased cardiovascular risks of Vioxx,
he was told that his conclusions were too strongly worded.
"Dr. Graham described an environment
where he was 'ostracized,' 'subjected to veiled threats'
and 'intimidation,' " reported Senator Chuck Grassley
(Republican-Iowa) in a statement issued by his office.
The senator continued, "Instead of acting as a public
watchdog, the Food and Drug Administration was busy
challenging its own expert."
The power of advertising. While
some doctors argue that direct-to-consumer advertising
has helped educate patients, the fact of the matter is
that since the FDA loosened the prohibitions against
it in 1997, the dollars spent on marketing drugs directly
to the public have skyrocketed. Vioxx became a best-selling
drug largely due to the strength of TV, newspaper and
magazine ads. Sales of Vioxx were definitely fueled and
amplified by direct-to-consumer advertising, confirms Dr.
Topol. He believes that there should be no direct-to-consumer
advertising unless it is a question of survival -- for example,
to prevent a heart attack or stroke. In his opinion, these
ads should not be permitted for quality-of-life issues, such
as relief of arthritis pain or erectile dysfunction.
On a related note, you must be on guard
when your doctor writes a prescription for a new drug. (See
Daily Health News, September 23, 2004.) Doctors have become
increasingly reliant on the pharmaceutical companies to educate
them about new drugs. Our sister publication, Bottom Line/Health,
spoke with Marcia Angell, MD, former editor-in-chief of The New
England Journal of Medicine and author of a very powerful new
book entitled, The Truth About the Drug Companies: How They
Deceive Us and What To Do About It. In her book, Dr. Angell
details how deeply dependent doctors are on the pharmaceutical
companies for education. In 2001, drug companies paid more than
60% of the costs for continuing medical education for doctors.
In addition, there is roughly a 1:6 ratio of sales reps to
practicing physicians in this country. These reps attend
medical conferences and give doctors such "boondoggles"
as fine dinners, tickets to sports events and family vacations.
When it comes to drugs, newer is not
necessarily better. Ask your physician to prescribe medicines
that are not only effective for your condition but that also
have the longest track record for safety. When available,
also request less expensive generic and over-the-counter
alternatives.
THE FDA MUST DO MORE
Congress is looking more closely
into the internal workings of the FDA, in an effort
to ensure that the conclusions of its own safety experts
receive proper consideration.
Additionally, scientists and doctors
emphasize that the FDA must take steps to monitor the
safety of a drug once it arrives on the market. Dr. Topol
notes that Vioxx was approved after being used in a clinical
trial that involved fewer than 1,000 patients. After its
approval, millions of people suddenly were taking it, but
the close surveillance was at an end. Once a drug hits the
market, the FDA's monitoring is more reactive than proactive --
that is, it primarily responds to reports of adverse events.
In the future, Dr. Topol believes that we
need a stronger regulatory agency that will more closely
monitor and respond to possible health risks once a drug has
been approved... compel drug companies to conduct appropriate
clinical trials, even after the drugs are on the market... and
permit direct-to-consumer advertising only when there are
substantial health benefits and negligible risks.
On November 5, 2004, the FDA announced
the intention to address mounting safety concerns and
restore public confidence in its surveillance system. To
that end, it is sponsoring an Institute of Medicine (IOM)
study of the United States drug safety system, with an emphasis
on the post-market phase. The FDA also is providing an improved
decision-making process to make certain that the views of all
scientific reviewers are heard, and conducting a national
search to hire a new Director of the Office of Drug Safety
(a position that has remained conspicuously vacant for
more than a year).
Eric J. Topol, MD, chairman, department
of cardiovascular medicine, The Cleveland Clinic, Ohio.
